Dissolution experiments were performed using the paddle method with 900 ml of dissolution media at 37.0 ± 0.5 °C and 50 rpm rotation speed of the paddles. Caplets were carefully cut into slices, measured and weight as in the hydration experiments. Release kinetics was measured at regular time intervals. 10 ml samples were taken and measured using a UV/vis spectrophotometer (S-22 Boeco, Boeckel and Co., Hamburg, Germany) at 243 and 314 nm corresponding to the λmax of respectively paracetamol and ranitidine. Because indomethacin has a low saturation concentration in water, a biphasic dissolution method needed to be applied on indomethacin loaded caplets to keep the chemical potential difference between the sample and the dissolution medium constant. Caplets were immersed in 600 ml medium, while on top a 300 ml octanol phase was present. Release was measured in the octanol phase by UV/vis at 319 nm, corresponding to a λmax of indomethacin. In dissolution media where pH is above pKa (which is around 4.2) indomethacin is negatively charged, which could decrease uptake in octanol and theoretically disrupt the test. However when testing the release of drug crystals at pH of 6.8, it was found to be very fast compared to other pH’s as can be seen in Figure 8C. Therefore we have no reason to believe the charge of the drug will be disruptive for the test. RESULTS AND DISCUSSION Drug-zein compatibility As zein protein has a complex structure, it is not possible to use theoretical Flory-Huggins based drug-excipient miscibility prediction methods, such as ground contribution and solubility parameters methods21, to assess the compatibility between zein and the model drugs. A first indicator for the drug-matrix compatibility is the influence of drug loading on the processability during hot-melt extrusion-injection moulding (HME-IM), as reflected by
Dissolution experiments were performed using the paddle method with 900 ml of dissolution media at 37.0 ± 0.5 °C and 50 rpm rotation speed of the paddles. Caplets were carefully cut into slices, measured and weight as in the hydration experiments. Release kinetics was measured at regular time intervals. 10 ml samples were taken and measured using a UV/vis spectrophotometer (S-22 Boeco, Boeckel and Co., Hamburg, Germany) at 243 and 314 nm corresponding to the λmax of respectively paracetamol and ranitidine. Because indomethacin has a low saturation concentration in water, a biphasic dissolution method needed to be applied on indomethacin loaded caplets to keep the chemical potential difference between the sample and the dissolution medium constant. Caplets were immersed in 600 ml medium, while on top a 300 ml octanol phase was present. Release was measured in the octanol phase by UV/vis at 319 nm, corresponding to a λmax of indomethacin. In dissolution media where pH is above pKa (which is around 4.2) indomethacin is negatively charged, which could decrease uptake in octanol and theoretically disrupt the test. However when testing the release of drug crystals at pH of 6.8, it was found to be very fast compared to other pH’s as can be seen in Figure 8C. Therefore we have no reason to believe the charge of the drug will be disruptive for the test. RESULTS AND DISCUSSION Drug-zein compatibility As zein protein has a complex structure, it is not possible to use theoretical Flory-Huggins based drug-excipient miscibility prediction methods, such as ground contribution and solubility parameters methods21, to assess the compatibility between zein and the model drugs. A first indicator for the drug-matrix compatibility is the influence of drug loading on the processability during hot-melt extrusion-injection moulding (HME-IM), as reflected by