In general, the objective of a drug delivery system is to provide an effective therapeutic amount of a drug to a targeted site in the body to quickly obtain, and then maintain, the desired drug concentration. Two considerations of drug delivery are spatial placement and temporal delivery of a drug; spatial placement relates to the targeting of a drug to a specific organ or tissue, while temporal delivery refers to controlling the rate of drug delivery to the target tissue.
A number of drugs require more than one administration during the day in order to maintain a desirable plasma concentration. One problem experienced with such drugs is that more than one dosing a day can affect patient compliance, especially in pediatric patients. By way of example, ADDERALL®, which is indicated for treatment of Attention Deficit Hyperactivity Disorder in children from 3-10 years of age, has a disadvantage that two separate doses are administered, one in the morning and one approximately 4-6 hours later, commonly away from home under other than parental supervision. This form of treatment, therefore, requires a second treatment which is time-consuming and inconvenient. As another example, the greatest incidence of cardiovascular disorders including angina, stroke, heart attack, etc., typically occur during the early morning hours when blood pressure is rising in response to natural circadian rhythm. Accordingly, there are numerous instances where it would be beneficial to have a formulation which can provide two or more doses, delivered at different times.
A number of various pharmaceutical formulations have been developed to minimize the number of doses required to be taken each day, such as sustained and pulsatile formulations. To a first approximation, sustained release compositions are designed to provide a release of the pharmaceutical over an extended period of time. In contrast, pulsatile release compositions are designed to provide one or more release pulses separated by time and/or sites; for example, a pulsatile release composition may be designed to provide an immediate release pulse in the stomach and a second release pulse, delayed from the first by several hours, in the small intestine. See, e.g., Burnside et al., U.S. Pat. No. 6,322,819 B1.
A number of factors may influence the efficacy of pulse drug release and thus, represent a source of variability. Such factors include the complexity of the process for drug formulation, reproducibility of the manufacturing process, and uniformity of the product produced by the manufacturing process. In addition, gastrointestinal transit times vary not only from patient-to-patient but also within patients as a result of food intake, stress, and illness. Thus, while a variety of pulse release formulations have been proposed in consideration of one or more of these factors, room nevertheless remains for further improvement.