Studies On The Development Of Intragastric Floating And Pulsatile Release System

Using current release technology, it is possible for many drugs oral delivery for a pulsed or pulsatile release, which is defined as the rapid and transient release of a certain amount of molecules within a short time-period immediately after a predetermined off-release period. However, the substance must be absorbed well throughout the whole regions of the gastrointestinal tract since the GI region where drug released could not be controlled for the current pulsatile release system. A significant obstacle may arise if there is a narrow window for drug absorption in the gastrointestinal tract, or the drug is poorly soluble in the intestine. Furthermore, the majority of drugs are preferentially absorbed in the upper part of the small intestine and the relatively brief gastric emptying time in humans, which normally averages 2–3 h through the major absorption zone (stomach or upper part of the intestine),can result in incomplete drug absorption from the pulsatile release system with more than 3 h lag time. Thus may lead to diminished efficacy of the administered dose. So the real issue in the development of oral pulsatile release dosage forms is not just to a achieve lag-time before release, but to prolong the presence of the dosage forms in the stomach or somewhere in the upper small intestine until the drug is released after a predetermined period. On the other hand, pulsatile drug delivery is recognized as a satisfactory based on clinical cases and chronopharmacology theory. But how to appropriately control the predetermined lag time in vivo always brings about great puzzles in the research. Most pulsatile delivery systems are reservoir devices covered with a barrier coating, which dissolves, erodes or ruptures after a certain time period, followed by rapid drug release from the reservoir. Several single-unit pulsatile dosage forms with a capsular design have been developed, releasing the drug in a pulsatile fashion either after ejection or erosion of a plug or a capsule half. The working mechanism of these current pulsatile release systems is based on the exploitation of the peculiar interaction between a swellable or erodible hydrophilic polymeric coating and the aqueous gastrointestinal fluids. Time of interaction between the dosage form and the aqueous gastrointestinal fluids is a critcal factor for the lag time of the pulsatile release system. While considering the role of the influence of the biological environment on the release performance of pulsatile delivery system, control of placement of a dosage form in a specific region of the GI tract before the drug released offers numerous advantages, especially for include a reproducible of its lag time in vivo.Overall, These considerations have led to the development of oral pulsatile release dosage forms possessing gastric retention capabilities. Oral pulsatile release dosage forms with hydrodynamically balanced systems possessing gastric retention capabilities have a bulk density lower than gastric fluids and thus remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time. While the system is floating on the gastric contents, interaction between the system and the aqueous gastrointestinal fluids would be retained until the release of drug. After the release of drug, the residual system is emptied from the stomach. This results in an increase in the gastric residence time and a better control of the lag time of the oral pulsatile release system.We developed three kinds of oral pulsatile release dosage forms possessing gastric retention capabilities.First, a multifunctional drug delivery system, which was designed as a pulsatile and floating drug delivery system , was developed and evaluated. Such drug delivery system is developed from the pulsatile system described by Krogel and Bodmeier. The novel system consists of a hydrophilic matrix tablet placed within an impermeable polymeric cylinder closed with an erodible drug-free plug and an air-filled space or floating material filled at the bottom. When...