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Solid lipid nanoparticles with enteric coating for improving stability, palatability, and oral bioavailability of enrofloxacin
Authors Li C, Zhou KX, Chen D, Xu W, Tao Y, Pan Y, Meng K, Shabbir MAB, Liu Q, Huang L, Xie S
Accepted for publication 19 October 2018
Published 1 March 2019 Volume 2019:14 Pages 1619—1631
Editor who approved publication: Dr Mian Wang
Chao Li,1 Kaixiang Zhou,1 Dongmei Chen,1,2 Wei Xu,1 Yanfei Tao,1 Yuanhu Pan,2 Kuiyu Meng,2 Muhammad Abu Bakr Shabbir,2 Qianying Liu,1 Lingli Huang,2 Shuyu Xie1
1National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan Hubei, China; 2MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, Wuhan Hubei, China
Background: The poor palatability, variable oral bioavailability, stimulation to gastric mucosa, and light instability limited the application of enrofloxacin (ENR). The enteric granules combining solid lipid nanoparticles (SLNs) with enteric coating were explored to overcome these disadvantages.
Materials and methods: ENR-loaded SLNs were produced by a hot homogenization and ultrasonic emulsification method and the enteric granules with SLNs as inner core were prepared by wet granulation followed by coating using polyacrylic resin II (PRII). The formulation was optimized by using orthogonal or single factor test screening.
Results: The optimal SLNs with loading capacity (LC) and price as inspection indexes were consisted of 10 mL 3% polyvinyl alcohol per 0.8 g ENR and 2.4 g octadecanoic acid. The sizes, LC, polydispersion index, and zeta potential of the SLNs were 308.5±6.3 nm, 15.73%±0.31%, 0.352±0.015, and -22.3 mv, respectively. The best enteric granules were used 15% PRII as coating materials. The release of the enteric granules in simulated intestine fluid (SIF, pH=8) was significantly faster than in simulated gastric fluid (SGF, pH=2) and simultaneously slower than those of SLNs and native ENR. The granules showed good stability in influencing factor experiment. The granules displayed a similar daily feed intake as the control group and higher daily feed intake than ENR powder and single-coating granules. Compared to the ENR soluble powder, the area under the plasma concentration–time curve and mean retention time of the enteric granules after intragastric administration were increased from 4.26±0.85 µg h/mL and 6.80±2.28 hours to 11.24±3.33 µg h/mL and 17.97±4.01 hours, respectively.
Conclusion: The enteric granules combination SLNs with enteric coating significantly improved the stability, palatability, sustained-release performance and oral bioavailability of ENR. The novel technology will be a potential measure to overcome the similar disadvantages of other drugs.
Keywords: enrofloxacin, solid lipid nanoparticles, enteric coating, palatability, bioavailability, light stability
Enrofloxacin (ENR), known as ethyl ciprofloxacin, is the first animal-specific fluoroquinolone and successfully developed by Bayer AG of Germany.1 It has been widely used in veterinary clinic because of its broad antibacterial spectrum, strong bactericidal activity, low adverse reactions, and high postantibacterial effect.2 However, ENR has a bitter taste.3,4 The poor palatability limits its oral administration since the animals with keen sense tastes, especially for pigs and cows, exhibit more possibility to refuse the bitter drugs.5 Oral formulations currently available in market cannot mask the bitter taste of ENR and thus limit the oral clinical applications for pigs. In addition, the drug has short elimination half-life (T1/2β) and mean residence time (MRT) in most mammals and variable bioavailability due to its poor aqueous solubility. Therefore, the control-release formulation with good palatability, little gastric irritation, and improved absorption is necessary.
Some taste-masking formulations were prepared to improve the palatability of ENR. Chun et al prepared a ENR carbopol complex to mask the bitter taste, while its taste-masking effect is uncertain due to lack of direct animal experiment.4 The double-coated ENR microparticles might effectively mask the bitter of ENR but the release data of microparticles in simulated gastric fluid (SGF) were not provided.3 The formulations prepared by hydrogel materials (sodium alginate, chitosan) had a low pH-dependent release.6,7 So the bulk release of these hydrogel preparations in SGF might result in stomach irritation due to the irritant effect ofenrofloxacin on the gastric mucosa. This might influence animal oral compliance. The reduction of ENR release in stomach might be a potential way to achieve excellent release since ENR has a maximum solubility in low pH (>100 mg/mL in pH=1).8 EC Besides, ENR has high photolysis.9 It should be stored away from light and thus increases the storage and transportation costs. Therefore, the development of a new dosage with good palatability, low stimulation to stomach and good stability is urgent for ENR.
Solid lipid nanoparticles (SLNs) are a novel nanosized drug delivery system using high-melting natural or synthetic solid lipids as backbone materials because of their good physiological compatibility and outstanding physicochemical property (nanosize and large specific surface area effect).10 It is often used to improve the permeability and palatability,11 achieve controlling release,12,13 and enhance oral bioavailability.14 However, the release of ENR from SLNs in stomach is very rapid due to the maximum solubility of ENR in gastric juice. In addition, the SLNs could not completely entrap the drug. Therefore, mere nanoparticles may not effectively decrease the release of ENR in stomach and achieve the best sustained release and entirely mask the bitter taste.
Coating technology including enteric coating is a production process in which macromolecule material is wrapped on drugs by chemical or physical method.15 After coating, the contact chance between the drug and the taste buds of animal is reduced,16 and the drug could be isolated from direct exposure of the natural light. The coating of functional materials (ie, water-insoluble, enteric-soluble materials) can impart specific target release properties of drug in the gastrointestinal tract. In recent years, coating techniques have been widely used to increase the palatability and delivery of drugs to specific target sites. Choi and Kim coated the peonja using Eudragit acrylic resin, which well masked the bitterness of the drug.17 It was also reported that the taste of gabapentin was significantly improved when coated with the mixture of gelatin, partially hydrogenated soybean oil, and glyceryl monostearate.18 Alsulays et al reported that the cumulative release of lansoprazole enteric coated was <10% in the acidic condition, while up to 80% in the alkaline buffer stage.19 The stability of all-trans-retinoic acid by fluid-bed coating under high illumination (4,500±500 lx) was reported to be enhanced.20 However, the simple coating might not remarkably improve the palatability because of the greatest bitterness of ENR. It happens that coating tablets or granules with enteric materials might reduce the dissolution of drug in stomach but not obtain sufficient taste masking.
In order to overcome the disadvantages of insufficient taste masking and controlled release performance of simple coating and SLNs, ENR taste-masking enteric granules were creatively prepared by combining SLNs with coating in this study. The formulation was optimized by using orthogonal test or single factor screening. The properties, stability, palatability, and the sustained release in vitro and in vivo were further evaluated.
ENR standard (98% ENR content) was bought from Dr Ehrenstorfer. ENR (≥96.0% ENR content) was purchased from Wuhan Konglong Century Technology Development Co., Ltd. (Wuhan, China). ENR soluble powder was purchased from Guangdong Wens Dahuanong Biotechnology Co., Ltd. (Guangdong, China). Octadecanoic acid and docosanoic acid were obtained from Aladdin (Shanghai, China). Polyvinyl alcohol (PVA) and poloxamer 188 were bought from Sigma (St. Louis, MO, USA). Polyvinyl pyrrolidone (PVPK30) was obtained from Sinopharm Group Chemical Reagent Co., Ltd. (Shanghai, China). Polyacryl resin II (PRII) was purchased from Shanghai Source Biological Technology Co., Ltd (Shanghai, China). Ethyl cellulose (EC) and sodium carboxymethyl cellulose were purchased from Sinopharm Group Chemical Reagent Co., Ltd.
Twenty-seven clinically healthy three-way hybrid pigs (15–20 kg) were obtained from Huazhong Agricultural University (HAZU) Livestock Engineering Center (Wuhan, China). The pigs were acclimatized at laboratory animal rooms at the National Reference Laboratory of Veterinary Drug Residues (HZAU) and were freely fed on drug-free feed and made to drink for 1 week. The relative humidity and temperature of the breeding environment were maintained at 45%–65% and 18°C–25°C, respectively. All the experimental protocols were authorized by the Institutional Animal Care and Use Committee at HAZU (approval number: HZAUSW-2018-009) and followed the guidelines of Hubei Science and Technology Agency.
Preparation of ENR enteric granules
The production process flow of the ENR enteric granules was shown in Figure 1.
Figure 1 The production process of enrofloxacin enteric granules containing SLNs inner core.
Abbreviations: ENR-SLNs, enrofloxacin-loaded SLNs; RT, room temperature; SLNs, solid lipid nanoparticles.
Preparation of ENR-loaded SLNs
The SLNs were produced by a hot melt homogenization with ultrasonic emulsification method. Briefly, a certain amount of ENR was dissolved in the melted solid lipid under stirring by a magnetic stirrer (9001, Shanghai Huxi Analysis Instrument Factory Co., Ltd., Shanghai, China). After complete dissolution, a certain volume and concentration of preheated emulsifier solution was swiftly poured into the above melted lipid solution under stirring to form a primary emulsion. The primary emulsion was sonicated using 6 mm microprobes with 95% amplitude (VCX 130 Vibra-CellTM, Sonics & Materials, Inc., Newtown, CT, USA) for 4 minutes to form a hot O/W emulsion. In the preparation process of O/W emulsion, the emulsifier was optimized by orthogonal experiment using drug loading capacity (LC) of SLNs as assessment index. The type, concentration, and volume of the emulsifiers were also selected as variables. The corresponding levels are PVA, PVP, poloxamer 188; 1%, 2%, 3%; 10 mL, 15 mL, 20 mL, respectively. After determination of the variables and their levels, the design of the orthogonal test was used SPSS software (version 20, IBM) (Table 1). In the orthogonal test, the composition of one to nine SLNs was 15 mL 3% PVA, 20 mL 3% poloxamer 188, 20 mL 2% PVA, 10 mL 1% PVA, 15 mL 1% poloxamer 188, 20 mL 1% PVP K30, 10 mL 3% PVP K30, 15 mL 2% PVP K30, and 10 mL 2% poloxamer 188 per 0.8 g ENR and 2.4 g octadecanoic acid, respectively. The hot O/W nanoemulsion was cooled down under the room temperature to form SLNs.
Table 1 Factors and levels of the L9 (34) orthogonal design
Abbreviations: PVA, polyvinyl alcohol; PVPK30, polyvinyl pyrrolidone K30.
Preparation of coating granules using SLNs as inner core
After formulation of the ENR-loaded SLNs (ENR-SLNs), a certain amount of sucrose and starch was, respectively, added into the nanosuspension during stirring to prepare preliminary soft material. The preliminary soft material was placed in a dry oven (DGX-9243B-1, Fuma Test Equipment CO., Ltd., Shanghai, China) (50°C, 4 hours) to prepare the suitable soft material for pelletizing. After pelletized by using granulator (YK-60, Zhongcheng Pharmacy Machine Co., Ltd., Changsha, China), the prepared granules were dried again (50°C, 1 hour) to remove the water. The dry granules were coated with 10% (W/W) ethyl cellulose or 5%, 10%, and 15% (W/W) polyacrylic resin (PRII) using coating pan (BY-400, Zhongcheng Pharmacy Machine Co., Ltd.). After coating, the ENR taste-masking enteric granules were obtained. The optimal content of PRII for coating was evaluated by in vitro release performance.
Preparation of simple coating enteric granules
The preparation process of simple coating enteric granules was the same as the above ENR double taste-masking enteric granules except the process of production of ENR-SLNs. Briefly, 60% starch, 15% sucrose, and 10% ENR were completely mixed. Then, 5% starch using as an adhesive agent was produced into starch paste with 50 mL water by boiling method. The prepared starch paste was mixed with the above mixture and formed granules via pelletizing. The granules were coated by 10% PRII (750 mL 2% alcohol solution).
Characterization of ENR-SLNs
Determination of particle size, polydispersion index (PDI), and zeta potential
The morphology of SLNs was observed by scanning electron microscope (JSM-6390LV, NTC, Co., Ltd., Tokyo, Japan). The size, PDI, and zeta potential were measured by using Zetasizer ZX3600 (Malvern Instruments, Worcestershire, UK) and laser particle size analyzer BT-9300S (Better, Liaoning, China) at 25°C. The samples were diluted in distilled water to make sure that the concentration was 2.7 mg/mL for the tests of size and PDI, and 0.3 mg/mL for the measurement of zeta potential to get the optimum kilo counts per second of 20–400. All determinations were repeated in triplicate by using independent preparations.
Loading capacity (LC) and encapsulation efficiency (EE) of SLNs
The determination of LC and EE of SLNs was described in our previous work.21 Briefly, the nanosuspensions were collected by centrifugation at 14,000 rpm (Hitachi Centrifugation CR21GIII; Hitachi Koki Co., Ltd., Japan) for 60 minutes at 4°C. The free ENR in the supernatant was measured by Waters 2695 series HPLC equipped with Waters 2587 UV detector (Waters Corp., Milford, MA, USA) to determine the EE. The precipitated SLNs were resuspended in distilled water and lyophilized for 48 hours (Freeze Dry System; Labconco, Missouri USA) for determination of LC. After freeze drying, 10 mg dried nanoparticles were added in a 15 mL tube containing 10 mL acetonitrile/water solution (V/V; 1:1) and put in a boiling water bath to destroy the nanoparticles. The SLNs after heating was added to the volume of 10 mL and centrifuged at 8,000 rpm for 10 minutes. The supernatant after filtration was injected into HPLC for analysis. The assay was repeated in triplicate using different samples from in dependent preparations. The EE and LC were defined as follows:
In vitro release
In vitro release of the ENR granules was measured in SGF (pH=2, 100 mL contained 2.0 g NaCl and 3.2 g pepsin and then HCl was used to adjust the pH to 2) and simulated intestine fluid (SIF; pH=8, 1,000 mL SIF contained 6.8 g KH2PO3 and 10 g trypsin and then NaOH solution was used to adjust the pH to 8) of pigs by using Dissolution tester RC806 (Tianjing Tiandatianfa Co., Ltd. Tianjing, China). The maximum solubility of ENR in SGF and SIF was 1.99 and 0.31 mg/mL, respectively. According to the sink condition, 1 g enteric granules (contained 100 mg ENR) or 155 mg enteric granules (contained 15.5 mg ENR) (n=3) were placed in a dissolution cup containing 200 mL buffer at 38°C under rotating propeller stirring at 100 rpm. One milliliter of samples was periodically collected from the dissolution cup at fixed times to measure the released drug, and the same volume of fresh SGF or SIF was added after each sampling to keep a constant volume. The drug concentration in the release media was determined by HPLC. The cumulative release curve was plotted using the cumulative release rate and time as ordinate and abscissa. In vitro release of the ENR granules with different kinds of and content of coating materials were done to select the optimum formulation. The in vitro release of native ENR, ENR-SLNs, and simple coating granules were used as control using the same process. The granularity and drying loss of all the kinds of granules meet the requirement of Chinese Veterinary Pharmacopoeia (2015).22
Palatability experiment
The palatability of ENR enteric granules was studied by pig feeding and water intake experiment. Briefly, 15 pigs were randomly divided into five groups with each group consisting of 3 pigs. The five groups included blank group, ENR powder group, simple enteric-coated granules, ENR enteric granules with 10% sucrose, and ENR enteric granules with 15% sucrose groups. Before the experiment, the average daily feed intake of each group was determined for continuous 3 days to ensure that the selected pigs were healthy, had normal appetite and excluded the individual possible errors. In the experiment period, pigs were free to feed on medicated feed with different ENR formulations for continuous 5 days. At 9 am every day, the enough feed without or mixed ENR formulations was added into the trough, and the remainder feed was weighted at 9 am of the next day. The daily feed intake of each group was equal to the added feed of the first day minus the remaining feed of the next day. After 7 days cleaning periods of ending of the daily feed intake experiment, 6 pigs were randomly selected to study the palat of ENR-SLNs via the daily water intake for 5 days. Briefly, six pigs were randomly divided into control group and ENR-SLNs group (n=3). At 9 am every day, the excess drinking water without or mixed ENR-SLNs (corresponding 25 mg ENR/L) was added and the remainder was weighted at 9 am of the next day. The daily water intake of each group was equal to the added water volume of the first day minus the remaining water volume of the next day.
Evaluation of the granules
The granularity was tested by double sieve method according to the Chinese Veterinary Pharmacopoeia (2015). Briefly, 8.0 g of drugs were kept in a sieve with horizontal state and sifting by left and right for 3 minutes. The granules that cannot pass through the No 1 sieve with 2 mm pore diameter and powder that can pass through No 5 sieve with 0.2 mm pore diameter were weighed to calculate their proportions to the total granules.
Drying loss
ENR enteric-coated granules (8.0 g) were tiled in an open pan and placed in a drying oven with 40°C. At fixed time point, the granules were weighed until the weight of granules was kept constantly. The weight loss of the samples on drying was calculated from the added amount minus the remainders. The assay was repeated in triplicate using different batch preparations.
The stability of ENR enteric granules was evaluated by influencing factor experiment including high temperature, high humidity, and strong light. The enteric granules were placed in a container and then placed in the environment of 60°C and 40°C (high temperature test), 25°C and 90%±5% (humidity test), or 4,500±500 l× (illumination) for 10 days, respectively. Samples were taken on the fifth and tenth day to assess the change of their appearance, drug content, granularity, and in vitro release performance.
Twelve healthy pigs before experiment were randomly divided into two groups (ENR soluble powder group and enteric-coated granules group) with six pigs in each group. ENR enteric granules (content: 10%) and ENR soluble powder (Guangdong Wens, content: 5%), respectively, resuspended or dissolved in 20 mL CMCC-Na were administered to the pigs by intragastric administration with 2.5 mg/kg bw. Blood was collected from the anterior vena cava of the pigs, and blank plasma was collected prior to administration. After drug administration, the blood was collected at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24, 36, 48, and 72 hours. Three milliliters of blood were collected at each time point, placed in a centrifuge tube containing heparin sodium, and centrifuged at 4,000 r/min to separate the plasma. The drug concentration in the plasma was detected by HPLC after pretreatment.
Pharmacokinetic parameters were calculated by WinNonlin software (version 6.4; Pharsight Corporation, Mountain View, CA, USA). Through observation the plasma concentration–time profile, the maximum plasma concentration (Cmax) and time to reach Cmax (Tmax) were obtained. The area under the plasma concentration–time curve (AUC0–last) was determined using the log-linear trapezoidal rule.
Quantitative measurement of ENR
In order to quantitative measurement of ENR, 0.8 mL of plasma was measured into a 10 mL centrifuge tube containing 1.2 mL acetonitrile. The plasma and acetonitrile were thoroughly mixed under vortex for 2 minutes to precipitate protein and then centrifuged at 12,000 r/min for 20 minutes to take the supernatant. The supernatant was dried in nitrogen and reconstitute with 800 μL mobile phase. The liquid was filtered through a 0.22 μm filter and subjected to an HPLC (Waters Corp.) for detection. Chromatographic conditions were as follow: column: Agilent SB C18 (250 × 4.6 mm × 5 μm); detection wavelength: 278 nm; column temperature: 25°C; mobile phase: 0.1% formic acid (phase A) and acetonitrile (phase B) with the ratio of 86:14; flow rate: 1.00 mL/min; and injection volume: 40 μL. The content of ENR in solution and plasma was determined using a standard curve. The HPLC method was validated in terms of linearity, accuracy, precision, and limit of detection and quantitation. ENR had a linear range from 0.1 to 1.8 μg/mL (R2=0.9985). The limit of detection and quantitation were 0.025 and 0.08 μg/mL, respectively. The relative SD of precision was <2%, and the recovery rates of three different added concentrations were 96.8%–103.3%.
Data are presented as mean ± SD. Statistical significance was defined at P-value of 0.05 and 0.01 by the SPSS software (version 20, IBM).
Optimization of ENR-SLNs
The maximum solubility of ENR in both melted octadecanoic acid and docosanoic acid is 33.33%. Due to the cheap price, the octadecanoic acid was selected as lipid matrix. The optimal ratio of drug to lipid was 1:3. According to the analysis of orthogonal test, the size of ENR-SLNs was in the range of nanosize when the PVA was used as emulsifier. The PDI of sample 1 and 3 was 0.229±0.007 and 0.155±0.030, respectively while the other samples exceeded 0.5 (Table 2). The zeta potential of all the nine samples was negative. Considering the practicability of enteric granules, the LC was the most important to select the formulation. The factors influencing the LC were in the orders: emulsifier type > concentration > volume (Table 2). The final optimal aqueous phase is 10 mL of 3% PVA per 0.8 g ENR and 2.4 g octadecanoic acid.
Table 2 The optimization of emulsifier by orthogonal experiment
Notes: K1, K2, and K3 are the average of grade of LC for three levels in each factor; R is the different value between the max and mix of K1, K2, and K3 in each level.
Abbreviations: LC, loading capacity; PDI, polydispersion index.
Physicochemical properties of ENR-SLNs
As shown in Figure 2, scanning electron microscopy observation demonstrated that the ENR-SLNs were spherical in shape with relatively uniform distribution in bulk. The mean sizes, PDI, and zeta potential of the optimal SLNs were 308.5±6.3 nm, 0.352±0.015, and −22.3 mv, respectively. The LC and EE of the optimal SLNs were 15.73%±0.31% and 68.78%±1.35%, respectively. Then the ENR-SLNs with these physicochemical properties were used to later researches.
Figure 2 Scanning electron microscopy photographs of enrofloxacin-loaded SLNs.
Abbreviation: SLNs, solid lipid nanoparticles.
The effect of coating materials on in vitro release of granules
In vitro release of ENR-SLNs and enteric granules in SIF and SGF is shown in Figures 3 and 4. In the SGF (pH=2), the ENR-SLNs and simple coating granules showed a closed release profiles but slightly slower release rate compared to native ENR. Note that, 96.56% of native ENR was swiftly dissolved in the simulated SGF within 1 hour, while about 95.62% was released from the SLNs within 4 hours and 95.17% was released from the simple coating granules within 6 hours, suggesting that the sustained-release performance of ENR-SLNs and simple coating granules was not obvious. In vitro release of granules with different coating materials was significantly slower than those of the native ENR, ENR-SLNs, and simple coating granules (Figure 3). The release velocity of enteric granules was decreased with the increase of the PRII content from 5% to 15%. In order to achieve the slowest release in SGF, the 15% PRII was selected as the optimal coating material. When using the 10% ethyl cellulose, the release velocity of granules was the slowest compared to the other granules. Only half of the ENR was released from the granules within 36 hours.
Figure 3 The accumulation release profiles of SLNs and granules in the simulated SGF (pH=2) (n=3).
Abbreviations: EC, ethyl cellulose; ENR, enrofloxacin; ENR-SLNs, enrofloxacin-loaded SLNs; PR, polyacrylic resin; SGF, simulated gastric fluid; SLNs, solid lipid nanoparticles.
Figure 4 The accumulation release profiles of SLNs and granules in the simulated SIF (pH=8) (n=3).
Abbreviations: ENR, enrofloxacin; ENR-SLNs, enrofloxacin-loaded SLNs; PR, polyacrylic resin; SIF, simulated intestine fluid; SLNs, solid lipid nanoparticles.
In the SIF (pH=8), the ENR-SLNs showed a closed release profiles but slower release rate compared to native ENR (Figure 4). Note that, 97.15% native ENR was dissolved in the SIF within 4 hours, while the SLNs were released about 94.27% within 8 hours, suggesting that ENR-SLNs held a certain sustained-release performance than native ENR. The enteric granules with 15% PRII as coating materials were slower than those of the native ENR and ENR-SLNs and significantly swifter than those in the SGF (pH=2). These results demonstrated that the enteric granules, combined with SLNs with 15% PR coating had a positioning release in intestine.
Palatability of different ENR formulations
The normal daily feed intake and daily intake of feed medicated with different ENR formulations are shown in Table 3. The daily feed intake of pigs in different groups was similar during the first 3 days before experiment, suggesting that the selected pigs were physiologically consistent. During the experiment, the daily feed intake of pigs in the ENR powder group (5 mg/kg bw) was sharply decreased from about 1.5 kg/day to below 0.2 kg/day. In contrast, the daily feed intake of pigs in the granules group (consists of 10% or 15% sucrose) (5 mg/kg bw) showed no significant difference compared to those of control groups and the normal daily feed intake. In the simple enteric coating granules (5 mg/kg bw), the daily feed intake of pigs in the granules group was lower than those of control group and granules groups. The average of water intake of control group was 9.7±1.2 L/group/day, while the average daily water intake medicated with ENR-SLNs (25 mg/L) was decreased to 7.5±1.6 L/group/day. These results indicated that mere SLNs cannot completely overcome the palatability of ENR. The enteric granules combined SLNs with enteric-coating significantly improved the palatability of ENR and will help for the application of ENR in clinic.
Table 3 The daily feed intake of pigs (mean ± SD, n=3)
Notes: Control group was addition feed only; 10% granules was 10% sucrose included in granules; and 15% granules was 15% sucrose included in granules. aStatistical significance compared with control is P<0.01. bStatistical significance compared with feed mix ENR is P<0.01. cStatistical significance compared with simple coating is P<0.05. dStatistical significance compared with simple coating is P<0.01.
Abbreviation: ENR, enrofloxacin.
The properties of ENR enteric granules
The optimal ENR enteric granules formulation was used; 15% PRII as coating materials and 10% sucrose as flavoring agent. The ENR enteric granules were assessed following the Chinese Veterinary Pharmacopoeia (2015). The average total proportion of granules that pass through No 5 sieve and cannot pass through the No 1 sieve to the total granules was 7.60%±0.12%, which is less than the pharmacopeia requirement of 15%. So the size of most ENR enteric granules (92.4%) was 0.2–2 mm. The average proportion of weight loss on drying is 1.90%±0.10% and less than the pharmacopeia requirement of 2.0%.
Stability of granules
The results of influencing factor experiment of granules including high temperature, high humidity, and strong light are shown in Table 4. The appearance of enteric granules was white and not changed during the whole period of influencing factor experiment. In the strong light, only 4.89% and 6.0% of ENR in the granules was degraded after 5 and 10 days, respectively, while up to 15% and 20% of the native ENR was degraded after 5 and 10 days, respectively. These results demonstrated that the granules can improve the stability of ENR against high light. The ENR granules were stabile at high temperature of 40°C but slightly sensitive to the high temperature of 60°C. In the high humidity, 4.82% and 7.0% of ENR in the granules was degraded after 5 and 10 days, respectively. The granularity of ENR enteric granules showed no obvious change. The amount and granularity of ENR enteric granules met the requirements of Chinese Veterinary Pharmacopeia (labeled amount: 90%–110%, unqualified granularity: <15%) after 10-day influencing factor test. The release velocity of the ENR enteric granules under the condition of high temperature and high light for 5 and 10 days showed no obvious change while was slightly quicker under high humidity for 10 days (Figure 5). These results suggest that the enteric granules had good stability.
Table 4 The influence factor test of granules (mean ± SD, n=3)
Figure 5 The influence of influencing factors experiments to release ability of enteric granules (n=3).
Notes: (A) The influence of high temperature to release ability of enteric granules. (B) The influence of high humidity to release ability of enteric granules. (C) The influence of high light to release ability of enteric granules. HT: high temperature (40°C); HI: high humidity (25°C, 90%±5%); HL: high light (4,500±500 lx).
After intragastric administration of the granules, the ENR in plasma was swiftly reached to the peak concentrations of 0.52±0.05 μg/mL at 3.33±1.03 hours, then decreased slowly and sustained above 0.03 μg/mL for 72 hours. Comparatively, the soluble powder more quickly reached to the peak value of 0.60±0.12 μg/mL at 1.12±0.44 hours, and then declined rapidly to 0.03 μg/mL at 24 hours after intragastric administration (Figure 6). The pharmacokinetic parameters are shown in Table 5. The AUC0–last, T1/2β, and MRT of the granules were 11.24±3.33 μg h/mL, 12.59±3.53 hours, and 17.97±4.01 hours, respectively, while these parameters for soluble powder were 4.26±0.85 μg h/mL, 4.71±1.58 hours and 6.80±2.28 hours, respectively (Table 5). Compared to the soluble powder, the bioavailability, T1/2β, and MRT of the prepared ENR enteric granules were increased by 2.64-, 2.67-, and 2.64-folds, respectively. The results suggested that the prepared granules had sustained-release effect and improve the oral bioavailability of ENR.
Figure 6 The plasma enrofloxacin concentration profiles – time of the prepared granules and reference formulation (soluble powder) in pigs (n=6).
Notes: Granules: 10% enrofloxacin enteric granules; powder: 5% enrofloxacin soluble powder.
Table 5 Pharmacokinetic parameters for ENR after oral administration of ENR enteric granules and ENR soluble powder in pigs (mean ± SD, n=6)
Note: a,b,c,dStatistical significance compared with soluble powder is P<0.01.
Abbreviations: AUC0–last, area under the curve; CL, body clearance; Cmax, maximum plasma concentration; ENR, enrofloxacin; F, relative bioavailability; MRT, mean residence time; T1/2β, elimination half-life; Tmax, time to reach the Cmax.
Coating technologies and nanoparticles are always used to produce the function preparations with ability of controlled23,24 and target release25 and to improve the palatability of the poor-tasting drugs.26 However, the single-coating granules, tablets, capsules, and other formulations will be chewed up by animals. Thus, the coated drugs will be released and attached with the taste buds of animal mouth. This study also demonstrated that the daily feed intake of pig medicated with single-coating granules was improved compared to those medicated with ENR powder but still less compared to the control group. These results suggested that the single-coating granules did not completely solve the bitterness of ENR. It is reported that lipid nanoparticles are also effective ways to improve the palatability of bitter-tasting drug since the drugs can be encapsulated and distributed into lipid materials.3 Meanwhile, SLNs are often used to improve the oral bioavailability of encapsulated drugs because of the adhesion of the nanosize of the particles.27 However, SLNs could not completely entrap the drug and often hold a burst release, and thus the nanoparticles may not entirely mask the bitter taste of encapsulated drug. Our study also showed that the daily water intake of pigs in the octadecanoic acid nanosuspension group was slightly lower than those of normal pigs. In order to overcome the problems of poor palatability and variable bioavailability of ENR., the enteric coating granules were explored using the SLNs as inner core. The granules containing ENR-SLNs were prepared by wet granulation technology and followed by the coating using the polymer film-forming materials.
In the preparation of SLNs, the choice of lipid is crucial in the formulation design. Lipids must be selected based on their good ability to solubilize the encapsulated drug. Our previous work showed that the fatty acid has a high dissolution of ENR compared to the other melted lipids since ENR can be freely soluble in the acid solution.28 Considering the short-chain fatty acids with low melting point are inconvenient for storage and transportation, hexadecanoic acid, decanoic acid, and lauric acid were not within the scope of consideration. Therefore, the maximum solubility of ENR in melted long-chain fatty acids of octadecanoic acid and docosanoic acid was determined in order to select the optimum encapsulated lipid matrix. The octadecanoic acid was finally selected due to the cheap price and satisfactory solubility. In order to obtain the higher LC for satisfying the practicability in clinic, the emulsifier was optimized by using orthogonal experimental design. According to the LC, size, and PDI, the SLN optimal formulation with 10 mL 3% PVA was selected for further characterizations. After formulation of the ENR-SLNs, different amounts of sucrose and starch were added into the nanosupension as flavoring and diluter agents according to the previous report, palatability, and cheap price.
In order to achieve the best palatability and sustained release, different coating materials were selected and evaluated in vitro release. In the SGF (pH=2), the release of granules with different coating materials was significantly slower than those of the native ENR and ENR-SLNs. These results indicated that the granules with different amount of PRII were relatively stable in the gastric juice. The sustained release of granules with 5% and 10% PRII showed no significant difference while the granules with 15% PRII showed the slowest release in SGF. Therefore, 15% PRII content was used in the optimum formulation. When using 10% ethyl cellulose as coating materials, the release velocity of granules was the slowest compared to the granules with PRII as coating materials. However, ethyl cellulose is a kind of water-insoluble material, and its solubility is irrelevant with pH.29 According to the solubility of ENR, the granules with 10% ethyl cellulose will also release very slowly in the simulated SIF (pH=8). Considering the gastrointestinal emptying time of pigs (≤50 hours),30 the granules were formulated with 15% PRII but not using 10% ethyl cellulose. In addition, ENR is a kind of concentration-dependent antibiotic; the effective exertion of antibacterial activity needs high Cmax level. The release of granules with 15% PRII was slower than those of the native ENR and ENR-SLNs in the SGF (pH=2) but swifter than itself in the SIF (pH=8). The ENR might be released completely within the gastrointestinal emptying time of pigs and can keep higher Cmax than coating by ethyl cellulose. These results demonstrated the granules combining SLNs with 15% PRII coating had a positioning release in intestine and decreased stomach irritating. Although ethyl cellulose was not used as coating material in our research, we proved that ethyl cellulose could be used to prepare excellent sustain release preparation by coating time-dependent antibiotics (ie, macrolides). The release of ENR from the inner SLN might be due to the diffusion combined with erosion.31–33 The ENR-SLNs released very fast in the SGF (pH=2) due to the highest solubility in the acid condition. The burst release might be the swift dissolution of free and nonentrapped drug and absorbed ENR on surface. For enteric granules containing SLNs, the main mechanism of drug release might be diffusion from the semipermeable membrane of coating of PRII due to the insoluble properties of outer PRII in SGF. Due to the double obstruction, the rate of the enteric granules was significantly slower than the SLNs. In SIF, the outer PRII coating of the granules was quickly dissolved, which leads to the disintegration of the granules. The release velocity of the granules in SIF mainly depended on the rate of granules disintegration and the drug diffusion from SLNs. Therefore, the ENR in granules was released quickly in SIF than in the SGF.
The palatability of the granules coated with 15% PRII was evaluated. The daily feed intake of pigs in the granules combined with SLNs groups (consists of 10% or 15% sucrose) (5 mg/kg bw) was not statistically significantly different (P<0.01) compared to those of control groups and the normal daily feed intake and higher than those of ENR powder group and simple enteric coating granules group. In order to decrease the price of the formulation, 10% sucrose was used as flavoring agents. These results indicated that the enteric granules, which combined SLNs with enteric-coating significantly, improved the palatability of ENR and will help for the application of ENR in clinic.
The granularity and weight loss on drying of the ENR granules met the requirements of the Chinese Veterinary Pharmacopoeia (2015). The stability of the prepared enteric granules under high temperature, high humidity, and strong light was shown to be good. Furthermore, the granules could significantly improve the stability of ENR in the strong light. This might be due to the lucifugal effect of lipid and coating material. The appearance, drug content, and granularity range of the enteric granules showed no obvious changes under the high temperature and humidity and strong light. This result suggested that the prepared enteric granules have a good stability. The core materials of the enteric granules also include the SLN, sucrose, and starch. Therefore, it is not possible to merely investigate the change of the inner SLNs. The in vitro release change of the granules under the high temperature and humidity and strong light was compared to the release of the initial preparation to indirectly evaluate the stability of the inner SLNs. The in vitro release profiles of enteric granules showed no change except the condition of high humidity for 10 days. These suggest that the enteric granules had good stability under high temperature and light while slightly sensitive to high humidity. Therefore, good moisture-proof measures were needed in storage and transportation of ENR enteric granules. The good stability of the enteric granules might be due to the excellent stability of inner nanoparticles and the coating of PRII. It is reported by Wang et al that the octadecanoic acid nanosuspension showed an excellent stability at room temperature for 9 months with no changes of particle size and zeta potential and slightly decrease of LC.34 It is well known that the stability of nanoparticles in solid powder sates is better than those in liquid. The good stability of ENR-SLNs within enteric granules is predictable. Therefore, the stability of inner ENR-loaded octadecanoic acid SLNs was not separately studied in this study.
After intragastric administration, the prepared enteric granules had sustained-release effect with improved bioavailability. Compared to soluble powder, the bioavailability, T1/2β, and MRT of the prepared ENR enteric granules were increased by 2.64-, 2.67-, and 2.64-folds, respectively. The improved bioavailability, controlled release, and palatability of the enteric granules might be closely related with the gastrointestinal transit (Figure 7). When the granules were taken by pig, they will taste good due to the isolation of ENR and taste bud in mouth by octadecanoic acid encapsulation and PRII coating. When the granules subsequently reach stomach, the inner ENR of the enteric granules will be less released within the time of gastric empty (2–6 hours) and will show little stimulation to the gastric mucosa. The increased bioavailability of the granules lessens the amount of ENR metabolized in stomach fluid resulting in more ENR reaching the intestine, . The granules begin to disintegrate due to the dissolution of outer layer PRII when they reach the small intestine whose pH is close to neutral by the gastric emptying. The inter ENR-SLNs were released following the granules disintegration. The granules showed higher oral bioavailability because of the high adhesion and permeability of ENR-SLNs due to the nanosize and large surface area.
Figure 7 The transfer process of enrofloxacin granules in gastrointestinal tract of pigs.
Abbreviations: ENR-SLNs, enrofloxacin-loaded SLNs; SLNs, solid lipid nanoparticles.
In our previous work, we proved that ENR-SLNs showed a good transmembrane transport and thus produced higher intracellular accumulation and stronger antibacterial activity as well as longer antibacterial time against intracellular Salmonella spp in vitro.21 The pharmacokinetics indicated that enteric granules have the similar Cmax compared with ENR soluble powder but longer maintenance time of blood concentration. The similar Cmax and enhanced absorption of the enteric granules and enhanced antibacterial activity of inner nanoparticles against intracellular bacterial will not easily induce the resistance and will be helpful for the treatment of intestinal infections by intracellular bacterial such as Salmonella and Intracellular Lawson bacteria. The pharmacodynamics and the effect of the enteric granules on the intestinal pathogens will be studied to evaluate the possible application in clinic in the future.
The optimum ENR enteric granules were formulated by the selection of lipid materials, emulsifiers, coating material, and other accessories by orthogonal test or single factor screening. The ENR enteric granules combining SLNs with enteric coating significantly improved the stability, palatability, controlled release, and oral bioavailability of ENR. The combination of SLNs and enteric coating will be a potential measure to increase the stability, palatability, sustained release, and bioavailability of other drugs.
This work was supported by the National Key Research and Development Program of China (2017YFD0501402) and the National Natural Science Foundation of China (grant no 31772797).
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Upon retirement, Marilyn and Gary Wenzel began volunteering at LCFS after seeing a presentation on the agency's mission.
Faith has always been an important part of Marilyn and Gary's lives. They met and graduated from Concordia University, River Forest. Both began their careers as Lutheran teachers. Gary eventually became the Dean of Arts and Sciences at Concordia, his alma mater, and Marilyn became a high school librarian.
No strangers to helping people with a hand up, Marilyn and Gary had become a safety net to a challenged but gifted music student at the high school where Marilyn worked. Mark came from a troubled family that was also economically challenged. When he was accepted to Berklee College of Music in Boston, he was unable to attend because the tuition was beyond his reach.
That's where the Wenzels came in. Berklee provided Mark with a sizable scholarship and the Wenzels felt compelled to help him financially by filling in the gap, so he could pursue his dreams.
"We decided to volunteer because LCFS is able to help thousands of people like Mark with a hand up. Through LCFS' See the Change presentation, we were able to see firsthand the change that the organization was having in people's lives," said Marilyn.
Recently, Gary and Marilyn met with their financial planner and decided to name LCFS as a beneficiary of their estate. "If faith is important to you and you are committed to nurturing and protecting children, strengthening families and making a difference, LCFS should be high on your list when making your lasting legacy gifts," said Gary.
With a planned gift to LCFS, you can combine your desire to give to charity with your overall financial, tax, and estate planning goals. You will help children and families in need - now and for years to come.


The oddest thing happens. I see multiple entries of the same library multiple times and have no idea on how to get rid of that. Anyone with an idea?
Hi, are there multiples in emby library setup?
Ok, please try removing it from library setup. Then run a library scan and see if they all go away. Please let me know if this helps. Thanks.
Hello. I did do that but they remain there.
as can be seen here.
Can you try running four library scans and see if they go away? thanks.
They did after two scans. Thank you.


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text:
← FNC #1 Cable Network & CBS #1 Broadcast Network Tuesday. BBC One #1 in the UK. Nine #1 in AU. UNI #1 Hispanic Net.
CBS #1 Friday in the U.S. Seven #1 in AU. →
CBS #1 Thursday in the U.S. BBC One # in the UK. Nine #1 in AU. TEL #1 Hispanic Net. FS1 #1 Cable Net.
Posted on October 21, 2016	by overtheshouldermlb
A Major Cyber Attack Is Hurting Twitter, Spotify, Pinterest, Etsy and Other Sites. According to AdWeek, 'wave of digital publishers and other ecommerce players were hit by a cyber attack this morning, causing their sites in some parts of the United States to go out in a problem that's lingering into middle afternoon. According to DownDetector—check out its map above—the East Coast and Southern California have been hit the hardest while Western Europe has also seen outages.
Notably, Twitter has been inaccessible to many users for hours, while Spotify, Pinterest, Shopify, SoundCloud have also experienced major outages. Additionally, Etsy, Reddit, Airbnb, GitHub, The New York Times and Boston Globe are down due to the ongoing outages, per TechCrunch. Hacker News is running an updated list of which sites are currently crashing.
The development seems particularly bad for the publishers like Twitter, Pinterest and NYT that rely on ad impressions for revenue, but the damage may be even worse for internet retailers Shopify and Etsy, which are likely losing sales.
The outages are apparently being caused by a "distributed denial of service" (DDoS) attack on web domains provider Dyn. Just before 2 p.m., the Ottawa-based company posted updated information related to the attacks, including the message: "Our engineers continue to investigate and mitigate several attacks aimed against the Dyn Managed DNS infrastructure."
'It's All About Screens.' This is the Daily Diary of Screens #dailydiaryofscreens 🇺🇸🇬🇧🇦🇺💻📱📺🎬. For Thursday, October 20, 2016.
CBS #1 broadcast network as 'Thursday Night Football' was the top broadcast program overall.
FS1 was the #1 cable network as 'MLB NCLS' featuring the Chicago Cubs vs Los Angeles Dodgers was the top cable program overall.
TEL #1 Hispanic network as 'Señora Acero 3:La Coyote' was the top Hispanic program.
In the UK, BBC One #1 as 'The Apprentice' top program.
In Australia, 'Nine' finished #1 broadcast network as 'Seven News' was the #1 newscast as 'The Bachelorette Australia' finished as the #1 program.
'The Accountant' #1 at the U.S. box office on the weekend 14-16 October 2016.
'Inferno' #1 at the International box office weekend 14-16 October 2016.
Movie ticket prices fell 2.5% in Q3 2016. Sales of movie theater ads jumped 13.4% in 2015 as it reached $716 million in advertising sales. There are 3.734 Billion Unique Mobile 68% Social Ad Clicks Are Now Mobile. Users as of this quarter, account for a 51% worldwide penetration. Direct uploads of user videos to Facebook now exceed YouTube.
The latest social media stats include this: Americans spend 25% of their time on social media. Facebook having 1.7 billion monthly users watching 8 billion videos each day. In addition, 81% of all shares come from Facebook. Instagram has 400 million users. 88% of Twitter users are on mobile. An average of 500 million tweets are sent every day with 320 million active users. The Google+1 button is hit 5 billion times per day. 80% of Internet users on Pinterest are female. Pinterest has 110 million monthly active users. LinkedIn has 347 million registered members with 100 million active users. Tumblr has 555 million users and Weibo has 100 million daily users. Skype has 300 million active users and there are 1.000 billion users on Whatsapp. With 900 million active users on Facebook Messenger, 60 billion messages are sent via Facebook Messenger and WhatsApp every day. Netflix now has 75 million streaming subscribers. QQ has 853 million active users. WeChat has 697 million active users while QZone has 640 million. Baidu Tieba has 300 million active users while Viber has 249 million. Sina Weibo has 222 million active users while Line has 215 million. Snapchat has 200 million users and 150 million users are active each day, watching 10 billion videos each day. YY has 122 million active users; VKontakte has 100 million active users as does BBM and Telegram.
Cliptomize continues to grow as it has 98,764 users and 145,456 clipbooks with 741,503 visitors and 415,038 unique visitors with over 3.359 million page views. 4 minutes 56 seconds average time spent on spent on site since the beginning. In October, average time spent on site is 4 minutes 41 seconds. Cliptomize For Business Service Bureau during recent NDA client campaign including 22 sends delivered a remarkable open rate of 49.79% and a click-through rate of 48.33% #clipit, #clip4biz🖇 Double Your Open Rate & Click-Through Rate Now!: http://www.cliptomize.com/Clipbook/View/250922?secret=h42qm2ns5g The First step to engagement is click-through 🆕 FRIDAY AUSTRALIAN OVERNIGHT TV RATINGS (*SEE BELOW)
Today, traditional TV still accounts for the lion's share of video viewing, but online and mobile are where the growth is. When managed together, TV/digital/mobile hold the potential to drive real impact for advertisers—enabling them to maximize the customers they reach and/or reinforce key messaging across screens. After all, 'It's all about screens'.
The Home Of #dailydiaryofscreens
For Thursday, October 20, 2016 (Posted on October 21, 2016)
CBS #1 Thursday as 'Thursday Night Football' featuring the Green Bay Packers beating the Chicago Bears 26-10.
The Tiffany Network
8P 'NFL Kick Off' at Lambeau Field in Green Bay finished with an average 7.977 million viewers.
830P 'NFL Thursday Night Football' featuring the Chicago Bears vs Green Bay Packers finished with an average 10.909 million viewers as the Packers won 26-10.
9P 'NFL Thursday Night Football' finished with an average 10.903 million viewers.
10P 'NFL Thursday Night Football' finished with an average 9.890 million viewers.
Murdoch's Sports Network had MLB and finished #2.
8P 'MLB NLCS' featuring the Chicago Cubs vs Los Angeles Dodgers finished with an average 7.180 million viewers.
The Alphabet Network
8P 'Grey's Anatomy' finished with an average 8.063 million viewers.
9P 'Notorious' finished with an average 3.980 million viewers.
10P 'How To Get Away With Murder' finished with an average 4.302 million viewers.
The Peacock Network
8P 'Superstore' finished with an average 4.145 million viewers.
830P 'The Good Place' finished with an average 3.768 million viewers.
9P 'Chicago Med' finished with an average 6.614 million viewers.
10P 'The Blacklist' finished with an average 5.342 million viewers with a Must See TV ON DEMAND/Streaming episode.
The Animal Network of Broadcast
8P 'Rocky Horror Picture Show' finished with an average 5.338 million viewers.
The Little Network That Couldn't
8P 'DC's Legends of Tomorrow' finished with an average 1.783 million viewers.
9P 'Supernatural' finished with an average 1.636 million viewers.
CBS finished #1 overall Thursday in prime time with an average 10.079 million viewers and a 6.2/11.
FS1 finished #2 overall as the #1 cable network in prime time on Thursday with an average 7.180 million viewers.
ABC finished with an average 5.448 million viewers and a 3.7/6.
NBC finished with an average 5.304 million viewers and a 3.5/6.
FOX finished with an average 4.949 million viewers and a 2.9/5.
FNC finished with an average 3.174 million viewers.
CNN finished with an average 2.754 million viewers.
NFL finished with an average 2.717 million viewers.
MSNBC finished with an average 2.378 million viewers.
The CW finished with an average 1.710 million viewers and a 1.1/2.
TEL finished with a 1.0/2 rating.
UNI finished with a 1.0/2 rating.
ESNP finished with an average 1.331 million viewers.
Today In Communication History
On this date in 1962, Cliff Richard appeared on the 'Ed Sullivan Show'.
He said it first….'Television'.
In 1900, the term 'television' is coined by Constantin Perskyi at the International Electricity Congress, part of the 1900 Paris Exhibition.
'We need to move on.'
Election Poll Results Today:http://bit.ly/TheSprintBegins Only 23 days until Election Tuesday #vote 🇺🇸🗳
Stores Are Still Preferred For Buying Furniture
The home furnishings category encompasses home decor and products like bedding, flatware and curtains, all of which are relatively inexpensive to ship, and larger products like furniture, mattresses and rugs, which often require delivery surcharges and which consumers prefer to see in person before buying, as explored in a new eMarketer report, "Furniture and Home Goods Retailers and Digital Commerce 2016: Trends and Benchmarks".
Consumers in the US prefer to buy most products in-store, according to May 2016 research from Salesforce. Nearly seven in 10 US internet users polled said they preferred to purchase their home goods in a brick-and-mortar store.
Home goods also had the highest percentage when it came to ecommerce sites (e.g., Amazon.com) as well—16% of respondents cited it as their preferred channel for purchasing, though not for retail or brand sites.
Furniture was a product category with one of the lowest levels of digital buying among US digital shoppers—14%—according to November 2015 polling by internet security platform Imperva Incapsula. With a tendency to be bulkier and higher in price compared with many other categories, mattresses and entertainment systems may still seem like riskier products to buy online.
However, in earlier stages along the path to purchase, these bigger, more expensive items are more likely to be researched online. A study conducted in August 2015 by Tenthwave Digital and The Organic Agency found that brand websites were the leading source for learning about large-size, high-cost products by a hefty margin (40.2%), likely because these sites are perceived to have the most accurate and detailed specs with the additional benefit of being able to research without any high-pressure sales tactics.
When digital buyers do decide to buy something from this sector, though, mobile plays a fairly significant role. In Q1 2016 comScore data, a little more than one-fifth of US digital sales in the furniture, appliances and equipment category, as well as home and garden, were conducted on mobile devices.
Digital/Mobile Research
Research shows that 42% of millennial shoppers check at least four sources when deciding on a purchase. That includes social media.
For Black Millennials, Social Media Hits Mainstream
Sarah Mahoney writing in Media Post, states that Nielsen's latest African American Consumer Report finds that Black Millennials are powering a shift in media use, and that among African Americans, the Gen Y club is flexing its muscle in new ways. Besides wielding considerable clout in mainstream content (FOX's 'Empire', and AMC's 'The Walking Dead'), this demographic's impact is also being felt in brand marketing and—no surprise here—the coming Presidential election. Their impact is considerable: Black Millennials, at some 11.5 million, represent 14% of all Millennials and 25% of the total Black population.
One of the most surprising findings in the report is the extent to which Black Millennials regard technology and social media as extensions of who they are, says Andrew McCaskill, Nielsen's SVP of global communications and multicultural marketing. "They have the propensity to use digital spaces as meeting places," he tells Marketing Daily, over-indexing for the number of hours they spend on their networks each day. Some 55% of Black Millennials in its research say they spend an hour or more per day on social media, or 11% higher than the overall Millennial population. And 29% say that they spend three or more hours per day, about 44% higher than that of the total Millennial group. "And when they're on social media, they're talking about everything from politics to products and services, as well as the way they're engaging with video content."
Part of that TV trend is that there is more and more for them to watch. "Content creators have picked up on the fact that African Americans are voracious consumers of video and TV, and that they want to see themselves in original content, as well as in advertising campaigns," he says. The more shows include either mainly Black casts or lead actors, the more these young audiences watch. Top shows include Empire, How to Get Away With Murder and The Walking Dead.
And because Millennials, overall, are the most diverse generation, those programming trends are following shifts in the real population. He cites both 'Black-ish', with 76% of its audience as non-African American, and 'Scandal', with 68% of viewers as not African American, as examples of this increasingly mainstream migration.
The report says advertisers are following the shift, with broadcast TV ad spending on programming with greater than 50% Black viewers jumping 255% between 2011 and 2015.
It's all led young Black consumers to become increasingly aware of their power, and brands to gain a deeper respect for both immediate economic impact and the promise of expanding influence. While much has been written about the impact of social change movements like #BlackLivesMatter and #OscarSoWhite, McCaskill's favorite recent example is #BankBlack, "where rapper Killer Mike, with a single tweet, was able to drive $1 million in new accounts at Black-owned banks."
Regarding the looming election, he says African-Americans "had the highest rate of voter registration and voter turnout of any demographic group in the U.S," a trend Nielsen expects to continue. "Black Millennials are owning their power in concerted ways," he says. "They are very optimistic, but also engaged in talking about all the things that are working and not working for them." Not that long ago, he points out, academics and experts talked about a digital gulf between Black and White America. "Now, between mobile phone usage and the drive of African American Millennials, that divide is closed."
Morning News Ratings Last Week 10 October 2016
Total Viewers:
#1 ABC's 'Good Morning America' finished with an average 4.477 million viewers.
#2 NBC's 'The Today Show' finished with an average 4.289 million viewers.
#3 CBS' 'The Morning Show' finished with an average 3.436 million viewers.
Evening News Ratings Last Week 10 October 2016
#1 ABC's 'World News Tonight with David Muir' finished with an average 8,290,000 million viewers UP 6% vs SW 2015. NOTE:World News ranks #1 in total audience for the first time in 17 years, since the 1999-00 season, and is drawing its largest overall viewer audience in 13 years, since the 2003-04 season (when Peter Jennings was in the chair).
#2 NBC's 'Nightly News with Lester Holt' finished with an average 8,045,000 million viewers UP + 9% vs SW 2015.
#3 CBS' 'Evening News with Scott Pelley' finished with an average 6,554,000 million viewers UP + 8% vs SW 2015.
Mobile/Digital Research
New Study Reveals Best Time To Show Ads
There's plenty of research and data that shows the best time to tweet or when to show your ads on Facebook or Google AdWords among other platforms. As per Joe Liebkind, writing in VentureBeat.com, posting at the right time ensures that you get to your target audience at the time they're most likely to view your content and take necessary action.
But content websites have had less guidance. What is the best time to present ads to your readers? What is the best content strategy that will ensure your website visitors make the most of your content and ad?
To better understand the behavior of users on content websites, CodeFuel — an engagement and monetization suite for publishers — and Nielsen conducted an online survey, published in September 2016, which reveals fascinating statistics about ad consumption preferences, preferred devices, and content consumption. If you know exactly what your users are doing throughout the day, you can make the most out of your ads.
The best time for content consumption
This is extremely important to all online marketers. As you fight for attention from your very busy audience, you need to give them what they want, at the right time. According to CodeFuel and Nielsen, this is how users are consuming content:
◉ 73% come just to get the latest updates
◉ 16% are taking a break
◉ 6% visit content sites for work/study
◉ 5% don't visit content websites at this time
◉ 47% come just to get the latest updates.
◉ 15% visit content sites for work/study
◉ 10% don't visit content websites at this time
Break time is the best time to show your audience ads because they are just browsing without a definitive goal. This research shows that at noon, 43% of users go and consume content without any other purpose.
Ad consumption preferences
The study further showed that:
◉ 79% of consumers prefer to access free or ad supported content
◉ 43% will watch an entire video ad if it has interesting content
◉ 39% click on an ad if it has an interesting offer
◉ 28% will click if it's an ad by a preferred brand
◉ 25% claimed that nothing would make them click on any ad
This shows that in your overall strategy, you should focus on building a solid brand reputation. Your ads should also always have an interesting offer to increase the clickthrough rates.
Which devices are your consumers using?
It is clear that people have migrated from stationary to mobile devices, leading to a huge growth in mobile advertising. PricewaterhouseCooper predicts that the Internet will soon overtake TV in advertising and that billions will be spent on the mobile market. As an advertiser, you cannot ignore the importance of mobile.
As much as there is cutthroat competition on mobile apps, the study revealed that users prefer mobile web over apps. 23% of users prefer using the browser on their mobile phones, while only 15% use mobile applications. For great impact, your ad should appear interesting in computers and all major phone browsers.
Why is it important to know what your audience is doing throughout the day?
People nowadays are focused on multi-tasking. They no longer just focus on one thing at a time. The rise of the Internet and smartphones has brought about new perspectives in the way people interact, look for information, or entertain themselves.
So, how do you get the attention of someone who is constantly tweeting, taking selfies, and chatting? You determine what times they're more likely to consume your ads. Know what format they prefer. Take a multifaceted approach in your content production strategy. Just like in any other business, production strategies should always match with possible consumption strategies.
Displaying ads when most people are working, studying, or not visiting sites will lead to lower clickthrough rates. This means advertisers get lower returns on their investments.
Displaying ads when people are looking for updates or when they're on break will increase clickthrough rates. This is the time when marketers should focus on getting most of their ads out there. Their clickthrough rates will increase, and they'll have higher chances of getting repeat visitors.
There will be more studies done to get specific attention metrics in different industries so as to improve ROI. Currently, attention metrics are in their infancy.
Due to the competition for attention, marketers will need to be more creative to increase attention to their content and ads. As this study shows, 43% of users will watch an interesting video and 39 percent will click on an ad if it has an interesting offer.
Entrepreneurs and businesses will need to work on improving brand trust. This will help them capitalize on the 28 percent of visitors who click on ads from a preferred brand.
There will be an increase in creating mobile-compatible content. Since everyone wants to do things on the go, even ads will need to be made in such a way that they will appear interesting on mobile.
Box Office Weekend 14-16 October 2016 (Domestic)
#1	'The Accountant' $24,715,000 in 3,322 locations
#2	'Kevin Hart:What Now?' $11,984,245 in 2,567 locations
#3	'The Girl On The Train' $11,974,915 in 3,241 locations
#4	'Miss Peregrine's'	$ 8,900,000 in 3,835 locations
#5	'Deep Water Horizon' $ 6,350,000 in 3,403 locations
Box Office Weekend 14-16 October 2016 (International)
#1 'Inferno' $50,000,000 in 53 territories
#2 'Miss Perregrine's' $23,500,000 in 73 territories
#3 'The BFG' $23,000,000 in 17 territories
#4 'Operation Mekong' $21,000,000 in 7 territories
#5 'Luck-Key' $12,500,000
'Doctor Strange' November 4, 2016
'Rogue One:A Star Wars Story' December 16, 2016
Welcome to new viewers in all 50 States of the U.S., all of the Provinces in Canada, all of the States in Mexico, the UK, Iceland, Ireland, Guernsey, Jersey, France, Belgium, the Netherlands, Denmark, Norway, Sweden, Finland, Estonia, Lithuania, Latvia, Estonia, the Russian Federation, Belarus, Ukraine, Republic of Moldova, Georgia, Poland, Germany, Austria, Czech Republic, Switzerland, Luxembourg, Portugal, Gibraltar, Spain, Monaco, Malta, Italy, Slovenia, Slovakia, Hungary, Romania, Bulgaria, Moldova, Croatia, Bosnia and Herzegovina, Serbia, Macedonia the former Yugoslave Republic, Albania, Montenegro, Greece, Cyprus, Turkey, Uzbekistan, Armenia, Azerbaijan, State of Palestine, Jordan, Lebanon, Israel, Saudi Arabia, Oman, Bahrain, United Arab Emirates, Qatar, Kuwait, Iraq, Uzbekistan, Pakistan, India, Bhutan, Nepal, Bangladesh, Sri Lanka, Kazakhstan, Mongolia, China, Hong Kong SAR China, Macao, Taiwan, Japan, Republic of Korea, the Philippines, Vietnam, Cambodia, Malaysia, Brunei Darussalam, Fiji, New Zealand, Australia, Indonesia, Singapore, Thailand, Mauritius, Zambia, United Republic of Tanzania, Kenya, Rwanda, Ethiopia, Egypt, Malta, Tunisia, Algeria, Libya, Morocco, Republic of Côte d'Ivoire, Mali, Gabon, Senegal, Benin, Nigeria, Cameroon, Ghana, Mozambique, Uganda, Namibia, Zimbabwe, Angola, South Africa, Argentina, Chile, Paraguay, Uruguay, Brazil, Bolivia, Peru, Ecuador, Colombia, Venezuela, Guyana, Suriname, Panama, Costa Rica, Guatemala, Honduras, El Salvadore, Belize, Curaçao, Aruba, St. Lucia, Grenada, Guadeloupe, Jamaica, Trinidad and Tobago, Dominica, Barbados, Haiti, the Dominican Republic, Martinique, U.S. Virgin Islands, British Virgin Islands, Bahamas, Cuba, Puerto Rico and Bermuda (155). We are thankful to all of you with more than 48,923 views. Top areas in the world viewing overtheshouldermedia on Friday came from the United States, the United Kingdom, Australia, Canada, France, Belgium, The Netherlands, Norway, European Union, Germany, Slovenia, Poland, Estonia, Switzerland, Portugal, Spain, Italy, Cyprus, Malta, Serbia, Saudi Arabia, India, Thailand, Indonesia, Singapore, South Korea, the Philippines, Vietnam, New Zealand, Egypt, Ethiopia, Nigeria, South Africa, Brazil, Chile, Columbia, Mexico, Costa Rica and Honduras.
BBC One #1 Thursday in the UK as 'The Apprentice' top program.
8P 'Anne Robinson's Britain' finished with an average 3.0 million viewers.
9P 'The Apprentice' finished with an average 5.3 million viewers and a 24.4% share.
The Little Two
8P 'Nature's Weirdest Events'
9P 'The Fall' finished with an average 2.0 million viewers and a 9.3% share.
The Independent One
8P 'Emmerdale'
830P 'Paul O'Grady's For The Love Of Dogs'
9P 'Paranoid' finished with an average 2.4 million viewers and an 11.1% share.
8P 'George Clarke's Amazing Spaces'
9P 'Hunted'
The Viacom Five
8P 'On Benefits'
9P 'Nightmare Neighbour Next Door'
NOTE: While Australian considers Prime Time 6P-Midnight, we use the US prime time system to measure television effectiveness in Australia. Thus 7P-10P is the standard from which this rating is based. Newscasts are considered only as newscasts and not television programs inside or outside of this period except in special periods.
Nine #1 Thursday in Australia as Ten's 'The Bachelorette Australia' was the top program.
The First Commercial Network in Australia finished with an average 597,000 viewers and a 25.1% share.
7P 'A Current Affair' finished with an average 663,000 viewers.
732P 'The Big Bang Theory' finished with an average 694,000 viewers.
8P 'The Big Bang Theory' rerun finished with an average 670,000 viewers.
830P 'Better Late Than Never' finished with an average 479,000 viewers.
929P 'Donald Trump Roast' did not finish in the top 20 programs.
The Third Commercial Network in Australia finished with an average 584,167 viewers and a 21.5% share.
7P 'The Project' finished with an average 539,000 viewers.
730P 'The Bachelorette Australia' finished #1 overall with an average 692,000 viewers.
910P 'Law & Order:SVU' finished with an average 445,000 viewers.
The Second Commercial Network in Australia finished with an average 546,000 viewers and a 28.3% share.
7P 'Home and Away' finished with an average 680,000 viewers.
8P 'The World's Angriest' finished with an average 413,000 viewers.
9P 'Guardian's of the Galaxy' did not finish in the top 20 programs.
The Alphabet Network in Australia finished with a 17.9 share.
730P '7.30' finished with an average 661,000 viewers.
801P 'Silvia's Italian Table' finished with an average 495,000 viewers.
833P 'National Treasure' did not finish in the top 20 programs.
922P 'The Tunnel:Sabotage' did not finish in the top 20 Programs.
The Special Broadcast Service in Australia finished #5 with an average 7.2% share.
730P 'Matthew Evans' For The Love Of Meat' did not finish in the top 20 programs.
830P 'Luke Nguyen's Street Food Asia' did not finish in the top 20 programs.
9P 'My Restaurant In India' did not finish in the top 20 programs.
930P 'Outlander' did not finish in the top 20 programs.
Top Newscasts In Australia Thursday
#1	SEVEN NEWS	Seven	938,000	viewers #1 in Brisbane, Adelaide & Perth
#2	SEVEN News/TodayTonight	Seven	882,000	viewers #1 in Sydney
#3	NINE NEWS	Nine	808,000	viewers #1 in Melbourne
#4	NINE NEWS 6:30	Nine	781,000	viewers Melbourne top market
#5	ABC NEWS ABC	732,000	viewers Melbourne top market
FRIDAY AUSTRALIAN OVERNIGHT TV RATINGS
src="https://overtheshouldermedia.files.wordpress.com/2016/09/988450-australian-passport.jpg?w=640″ alt="988450-australian-passport" width="640″ height="360″ class="alignnone size-large wp-image-16052″ />
Seven #1 Friday in Australia as 'Better Homes & Gardens' top program
The Second Commercial Network in Australia finished with a 32.3% share.
7P 'Better Homes and Gardens' finished with an average 774,000 viewers.
830P 'Martin Clunes: Islands Of Australia' finished with an average 634,000 viewers.
930P 'Selling Houses Australia' finished with an average 408,000 viewers
The First Commercial Network in Australia finished with a 25.1% share.
734P 'Ready For Takeoff' finished with an average 393,000 viewers.
835P 'Top Gun' did not finish in the top 20 programs.
The Alphabet Network in Australia and a 17.6% share.
801P 'QI' rerun finished with an average 407,000 viewers.
834P 'Code Of A Killer' finished with an average 485,000 viewers.
919P 'DCI Banks' finished with an average 436,000 viewers.
The Third Commercial Network in Australia finished with a 17.7% share.
730P 'The Living Room' finished with an average 469,000 viewers.
830P 'The Graham Norton Show' did not finish in the top 20 programs.
930P 'Have You Been Paying Attention?' did not finish in the top 20 programs.
The Special Broadcast Service in Australia finished #5 Friday with a 7.4% share.
735P 'Secrets Of The Tudors' did not finish in the top 20 programs.
830P 'Grace of Monaco' did not finish in the top 20 programs.
Top Newscasts In Australia Friday
#1	SEVEN NEWS	Seven	933,000	viewers #1 in Sydney, Adelaide & Perth
#2	SEVEN News/TodayTonight	Seven	862,000	viewers #1 in Melbourne
#3	NINE NEWS 6:30	Nine	775,000	viewers #1T in Brisbane
#4	NINE NEWS	Nine	774,000	viewers #1T in Brisbane
#6	EYEWITNESS NEWS 1st @5P	TEN	408,000	viewers Sydney & Melbourne top markets
For continual updates on all things 'screens', go to: https://www.facebook.com/pages/Dailydiaryofscreens
In this week's Media Notes Canonical, go to: http://bit.ly/1JnoNS6 🆕💭📝📎 It's FREE.
Media Notes Briefs: Mobile Consumption Dominating. Get It! Get Mobile-Friendly Now!!! 🆕💡💭🌎💬 – http://eepurl.com/ck4wdD
New This Week: Do Consumers Really Know What They Want? 💬 – http://sophis1234.tumblr.com
Weekly Retail Media Notes. This week: 'The Changing Manufacturer Evolution' http://www.furninfo.com/Furniture%20Industry%20News/6425 🆕💡💭🌎💬
Why Don't You Use Mobile Now? http://goo.gl/wlnJ8o
Today's featured 'Music To Read overtheshouldermedia By' down at the bottom of the page
Coachella Music Festival Paul McCartney
This entry was posted in Audience Analysis, Audience Behavior, Audience Management, Broadcast TV Ratings in Australia, Broadcast TV Ratings in the UK, Broadcast TV Ratings in US, Cable TV Ratings, Cinema, Daily Broadcast Ratings, Data, Digital, Direct, Hispanic TV Ratings, Late Night TV Ratings, Media, Media Analysis, Media Management, Mobile, Music To Read By, Music To Read overtheshouldermedia by, Television Program Renewals, Television Ratings, Thursday Night TV Ratings, Today In TV History, Uncategorized, Weekend Box Office and tagged 'Anne Robinson's Britain' TV Ratings in the UK Thursday, 'Australia Selling Homes' TV Ratings in Australia Friday, 'Better Homes & Garden's #1 program in Australia Friday 102116, 'Chicago Med' TV Ratings Thursday, 'Code of A Killer' TV Ratings in Australia Friday, 'DCI Banks' TV Ratings in Australia Friday, 'Grace of Monaco' Tv Ratings in Australia Friday, 'Green Bay Packers' TV Ratings Thursday 102016, 'Have You Been Paying Attention' TV Ratings in Australia Friday, 'Hunted' TV Ratings in the UK Thursday, 'Martin Clunes: Islands Of Australia' TV Ratings in Australia Friday, 'NFL Kick Off' TV Ratings Thursday 102016, 'NFL Thursday Night Football' #1 Thursday, 'NFL Thursday Night Football' TV Ratings Thursday 102016', 'Notorious' TV Ratings Thursday, 'On Benefits' TV Ratings in the UK Thursday, 'Paranoid' TV Ratings in the UK Thursday, 'QI' TV Ratings in Australia Friday, 'Secrets of the Tudors' TV Ratings in Australia Friday, 'Seven News' #1 newscast in Australia Thursday 102016, 'Seven News' #1 newscasts in Australia Friday 102116, 'Supernatural' TV Ratings Thursday, 'Superstore' TV Ratings Thursday, 'The Apprentice' #1 program in the UK Thursday 102016, 'The Bachelorette Australia' #1 program in Australia Thursday 102016, 'The Big Bang Theory' TV Ratings in Australia Thursday, 'The Good Place' TV Ratings Thursday, 'The Project' TV Ratings in Australia Friday, 'The Project' TV Ratings in Australia Thursday, 'The Rocky Horror Picture Show' TV Ratings Thursday, 'Top Gun' TV Ratings in Australia Friday, 7.30 TV Ratings in Australia Friday, 7.30 TV Ratings in Australia Thursday, A Current Affair TV Ratings in Australia Friday, A Current Affair TV Ratings in Australia Thursday, ABC TV Ratings in Australia Friday, ABC TV Ratings in Australia Thursday, ABC TV Ratings Thursday, BBC #1 in the UK Thursday 102016, BBC One TV Ratings in the UK Thursday, BBC Two TV Ratings in the UK Thursday, Box Office Weekend 14-16 October 2016 (Domestic), Box Office Weekend 14-16 October 2016 (International), CBS #1 Thursday 102016, CBS TV Ratings Thursday, Channel 4 TV Ratings in the UK Thursday, Channel 5 TV Ratings in the UK Thursday, Chicago Bears TV Ratings Thursday 102016, Chicago Cubs TV Ratings Thursday 102016, CNA|SOPHIS, DC's Legends of Tomorrow TV Ratings Thursday, Emmerdale TV Ratings in the UK Thursday, Evening News Ratings Last Week 10 October 2016 Total Viewers, For Black Millennials, FOX TV Ratings Thursday, FS1 TV Ratings Thursday 102016, Grey's Anatomy TV Ratings Thursday, Hispanic TV Ratings Thursday 102016, Home and Away TV Ratings in Australia Thursday, How To Get Away With Murder TV Ratings Thursday, ITV TV Ratings in the UK Thursday, Lance Hanish, Los Angeles Dodgers TV Ratings Thursday 102016, Major Cyber Attack On Many Social Media Sites Today, Morning News Ratings Last Week 10 October 2016, NBC TV Ratings Thursday, New Study Reveals Best Time To Show Ads, Nine #1 in AU Thursday 102016, Nine TV Ratings in Australia Friday, Nine TV Ratings Thursday in AU, Ready For Take Off TV Ratings in Australia Friday, SBS TV Ratings in Australia Friday, SBS TV Ratings in Australia Thursday, Seven #1 in Australia Friday 102116, Seven TV Ratings in Australia Friday, Seven TV Ratings in Australia Thursday, Social Media Hits Mainstream, Stores Are Still Preferred For Buying Furniture, TEL TV Ratings Thursday, Ten TV Ratings in Australia Friday, Ten TV Ratings in Australia Thursday, The best time for content consumption, The Blacklist TV Ratings Thursday, The CW TV Ratings Thursday, The Living Room TV Ratings in Australia Friday, UNI TV Ratings Thursday, Which devices are your consumers using?, Why is it important to know what your audience is doing throughout the day?. Bookmark the permalink.

redpajama_set_name: RedPajamaCommonCrawl


Cash Quest - The quest for cash is about to begin!
Your task in Cash Quest is to examine the world to uncover new items and abilities. Gather 50 precious items from 5 different stages and make your trading post into a super cash maker. Good luck!


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text:
Update: Grand Theft Auto V Announced on Jack Thompson's Disbarment Anniversary
Thread starter Greg Tito
Greg Tito
PR for Dungeons & Dragons
After years of speculation, Rockstar sends the first official word that GTAV is on its way.
Update: In what may or may not be a coincidence, careful internet observers noticed that Rockstar's announcement today coincides with the three-year anniversary of Jack Thompson's disbarment in the State of Florida. Thompson won his fame by suing Rockstar for selling "murder simulators" like Bully and GTA to minors, but his behavior in court belittling judges and defendants alike ended in his rights to argue in Florida courts being revoked in 2008. The effective date of Thompson's disbarment? October 25th. Well played, Rockstar.
Original Post: In 2001, Grand Theft Auto III sparked a revolution of open-world games and incited protests from groups saying it romanticized violence. The title catapulted Rockstar Games from a small shop in the U.K. to a worldwide brand. Follow-ups such as Vice City and San Andreas set in different cities sold extremely well, as did the first iteration on 7th generation consoles - GTAIV in 2008. After years of game journalists following parent company Rockstar's website today [http://www.escapistmagazine.com/news/view/112173-Take-Two-Plays-Coy-About-Next-Grand-Theft-Auto] shows the first official word of the hotly anticipated sequel.
Yep, just a logo. And a date for when we'll see a glimpse of the first official trailer on November 2nd, 2011. That's all we get, folks.
And yet, it's enough to get my blood pumping. Where will the game be set - back in Rockstar's version of New York Liberty City - or maybe a return to southern California in San Andreas? Personally, I'd love to see a GTA game set in Rockstar founders Dan and Sam Houser's hometown of London, England.
Obviously, we don't have much to go on here other than a new Grand Theft Auto logo. We don't have a release window or even know what platforms such a game will be on. My cash money's on the Wii U, but that's just me. I want to be able to take a cell phone call using that newfangled controller. [http://www.escapistmagazine.com/news/view/112261-Patent-Documents-Reveal-Wii-U-Controller-Details]
"Hey, Cousin!"
Source: Rockstar [http://www.rockstargames.com/]
Shamanic Rhythm
Please, no cousins. Please.
I'm actually excited, otherwise. Rockstar should consider picking an entirely untapped locale, like Chicago or Huston.
SomeLameStuff
What type of steak are you?
Greg Tito said:
newfangled controller.
Screwed that bit up there =P
Anyway, I hope it goes back to San Andreas style gameplay. GTA 4 was a little too... serious... for my liking.
Which is why I'll be getting Saint's Row 3.
Hybridwolf
Excellent. I do wonder if it'll be a two year job, but I roll on next week.
Doclector
Please let there be actual, y'know, fun things to do between missions.
LostCrusader
Lurker in the shadows
Don't think grand theft auto: London would work to well. Not very many standoffs with the cops would be very challenging since they wouldn't have guns.
XT inc
Go back to the old ways for five please, GTA 4 is why I own both Saints row games and am Getting the third.
Cousins, taxis to circumvent having to drive, only a tiny fraction of activities and character customization of the old games.
Sure the bank heist was awesome, but overall not to GTA'ee.
theriddlen
Well, GTA is always good, but the logo troubles me.
GTA IV had a great, classy logo. The V logo looks like someone taped the new number to the old logo - it just doesn't fit there.
Woodsey
"Personally, I'd love to see a GTA game set in Rockstar founders Dan and Sam Houser's hometown of London, England."
Doubt it; the styling on the V is pretty reminiscent of a five-dollar bill.
OT: As I said in the other thread, assuming they can fix almost every aspect of GTA IV - because it needs it, perfect scores my arse - I'll probably pick it up. Assuming the PC version isn't a fuck up like last time. And isn't 6 months late yet still full price, like last time.
Pipotchi
Ah I remember how excited I was when the first GTA4 trailers were coming in. "I have killed people, sold people"
I found Saints Row 2 a glitchy mess whilst I loved GTA, Saints Row 3 might be good though
Vrach
Doclector said:
^This. GTA IV wasn't so bad, it's just that it was so focused on the narrative, everything else was awful. And everything else being quite literally in your cellphone >.<
dagill
I'll only be happy when San Andreas gets a sequel. I want to jetpack over Area 51 wearing a pimp outfit and a chaingun. Not that GTA4 wasn't good, but it lacked a lot of the fun things from GTA:SA.
remnant_phoenix
Dear Rockstar,
New GTA? Meh.
When you make a new Red Dead, get back with me.
Still Standing Resolute Near John Marston's Grave
Doom972
This announcement doesn't really do much for me. I was sure they'll make this since they released GTA IV.
I hope they'll bring back some gameplay elements from San Andreas and the artistic style from Vice City.
Waaghpowa
Needs more Dakka
Why did they feel the need to put "five" over the Roman numeral? Redundant title is redundant, that or they assume people are stupid.
On a different note, no more bullshit with friends and cousins please.
Grouchy Imp_v1legacy
I'm just looking at the logo 'Grand Theft Auto V Five'. Apparently Rockstar believe we have the brainpower of undernourished spinach.
And this had better be a return to mindless fun and not another attempt at realism and man-dates.
Waaghpowa said:
That's the second time I've been ninja'd in three posts! Will you goddamn ninjas go and pick on someone else?!?
RonHiler
The polish is off the GTA franchise for me, after the disaster that was GTA IV. This definitely won't be a pre-order from me. It will wait until the game is out and I can see if it is going back to it's GTA III roots (in which case I will buy it for sure) or continues the horribleness that was IV (in which case I'll give it a pass and pop in SR3 for another playthrough).


PAWPOST: Basil has previously received one of their boxes and we were v. impressed with the quantity and quality of its content. Their boxes read like a who's who of premium, natural and eco-friendly pet brands, and they normally include a gift for the owner too. Essential info: for cats + dogs, one-off or subscription, lowest price £17.95 p/m.
THE ARTISAN PET DELI: this Deja Treat Box cuts straight to the chase focusing on what your dog probably loves the best, with three delicious packs of treats including biscuits, liver and venison. Plus for every sale, £1 is donated to All Dogs Matter. Essential info – for dogs, one-off gift only, priced £6.49.
VET BOX: a health-orientated box designed to keep on top of your pet's essential healthcare treatment for things like fleas and worms. Dependent on your pricing option, samples such as shampoo or ear cleaning products will also be added to your box. Great for sometime airheads like yours truly. Essential info: for cats + dogs, subscription service, prices start at £5.99.
BARK BEATS: the team at BB aim to delight their canine customers with products that are new to the market or not yet widely available in Europe to ensure your dog stays ahead of the pack, plus there's an emphasis on natural and biological treats. They also support smaller rescue homes and shelters around the UK with at least 10% of their profits. Essential info: for small, medium or large dogs only, one-off or subscription, lowest price £13 p/m.
Shop & Exclusive Offer: Barkarama readers can receive an exclusive 50% off their first Bark Beats Box at Barkbeats.co.uk. Enter the code Barkarama50 at checkout to claim. Valid until 31 December 2016 and cannot be used in conjunction with any other offers.
Giveaway: we also have two Bark Beats Boxes to giveaway. Visit our Bark Beats prize draw page for your chance to WIN! Closes 5 April 2016.
CHESHIRE & WAIN: especially for new kitties is this sweet New Cat Gift Selection box. Featured in the box is an Incomplete Book of Cat Names to inspire any naming struggles, a bag of loose of catnip to drive your pussycat wild and the brand's popular prawn catnip toy. Essential info: for cats, one-off gift, £25.
PURRFECT BOX / PAWESOME BOX: from the fun packaging featuring pet illustrations, quality contents of no less than six items of treats, toys and a feeder, plus the mini magazine that came with our delivery, the kitty version comes Catarama-brother approved. Essential info: for cats + dogs, one-off or subscription, lowest price £16.90.
TUX & TABBY: hip and handmade, you won't be rushing to hide away the contents when people come to visit. From chaser wands, cat-nipped filled toys and hoops, all items are made from natural materials such as sisal and birch. Essentials info: for cats, one-off gift only, New Cat Box shown is £26 but other options available.
TAILWAGGER: a cute community to be part of, the Tailwagger team are tight on making your box bespoke to your pet so say your dog is a serious toy destroyer, you'll never be sent a plush. They also offer options based on the number of items you'll receive in your box making it easier on price point. Essential info: for cats + dogs, one-off or subscription, from £13.99.
CAT HAMPURR: this one is just for kitties and the box we trialled had a heavy emphasis on treats and food but there are toys too. Cat Hampurr is great for their variety of purchase options, which caters to both your cat's demand and your budget with options including on-off gifts or bi-monthly/monthly or double subscription packages. Essential info: for cats only, various packages available, lowest price £8.