The main objective of this research was to better understand, predict and control of the periodic precipitation process and to apply such programmed periodic precipitation to the design of a pulsatile delivery system. In the first part of this study, a generalized model taking into account both nucleation, particle growth, and ripening process was refined and solved under various new concentration boundary conditions not previously investigated. The results clearly delineate the key differences between boundary conditions of infinite versus finite supply of inner electrolyte. When the inner electrolyte boundary concentration was allowed to increase exponentially with time, equidistant periodic precipitation was predicted and subsequently confirmed experimentally. In addition, the effects of product solubility and reaction rate constant were also shown to be important in determining the band number and band spacing. In the second part of this study, the effects of gel crosslinking and gel charge density on the periodic precipitation were investigated. The results indicate that by increasing either the gel crosslinking or decreasing the gel charge density will reduce the diffusion rate of the reactants resulting in closely spaced bands. In addition, a new and improved rotating disk method for characterizing polyelectrolyte gels with ion-penetrable soft surfaces has been established by taking into account the effect of surface conductivity which is usually ignored for ion-impenetrable hard surfaces. In the third part of this work, periodic precipitation formed in multi-component systems has been shown to be governed by a heterogeneous nucleation mechanism. Using this approach, periodic precipitation of an insulin mimetic compound VO2+ in gelatin gel, which cannot form alone in a single reaction system, was induced by the periodic precipitation of Mg(OH)2 in a multi-component system. Pulsatile release of VO2+ from the resulting multi-layered structure of VO(OH)2 via a surface erosion mechanism was subsequently demonstrated.

The main objective of this research was to better understand, predict and control of the periodic precipitation process and to apply such programmed periodic precipitation to the design of a pulsatile delivery system. In the first part of this study, a generalized model taking into account both nucleation, particle growth, and ripening process was refined and solved under various new concentration boundary conditions not previously investigated. The results clearly delineate the key differences between boundary conditions of infinite versus finite supply of inner electrolyte. When the inner electrolyte boundary concentration was allowed to increase exponentially with time, equidistant periodic precipitation was predicted and subsequently confirmed experimentally. In addition, the effects of product solubility and reaction rate constant were also shown to be important in determining the band number and band spacing. In the second part of this study, the effects of gel crosslinking and gel charge density on the periodic precipitation were investigated. The results indicate that by increasing either the gel crosslinking or decreasing the gel charge density will reduce the diffusion rate of the reactants resulting in closely spaced bands. In addition, a new and improved rotating disk method for characterizing polyelectrolyte gels with ion-penetrable soft surfaces has been established by taking into account the effect of surface conductivity which is usually ignored for ion-impenetrable hard surfaces. In the third part of this work, periodic precipitation formed in multi-component systems has been shown to be governed by a heterogeneous nucleation mechanism. Using this approach, periodic precipitation of an insulin mimetic compound VO2+ in gelatin gel, which cannot form alone in a single reaction system, was induced by the periodic precipitation of Mg(OH)2 in a multi-component system. Pulsatile release of VO2+ from the resulting multi-layered structure of VO(OH)2 via a surface erosion mechanism was subsequently demonstrated.

Multiple dose regimens are frequently required to optimize therapy; however, such therapy is frequently undermined by poor patient adherence. In fact, patient adherence is inversely related to the number of doses a patient is asked to take each drug. Consequently, great efforts are under way to develop drug delivery systems that are able to release drugs over an extended time interval; this could offer considerable benefits including reducing administration frequency. This dissertation describes multiple dose platforms designed to deliver a variety of drugs as a single oral administration are described in this dissertation. We believe these drug delivery systems can be used to enhance patient compliance and achieve better therapeutic outcomes. We developed and tested a novel gastroretentive pulsatile drug delivery platform. This platform could deliver multiple unit doses of a drug in a pulsatile pattern and be controlled by dissolution/erosion of a lag-time interval layer. The platform was designed to be retained in the stomach whilst pulsing drug at various timed intervals. This would allow each dose of the drug to release above or within an optimized absorption window over an extended period of time. To assure the robustness and reproducibility of the platform, various in vitro dissolution studies and physical stability tests were performed and evaluated through drug release characteristics, buoyancy, and structural integrity evaluations. The applicability of the novel multiple dose platform was demonstrated by providing repeated release profiles of ciprofloxacin and verapamil in a single, once-daily delivery system. Ultimately, this dissertation demonstrates that a novel multiple dose platform could be a suitable alternative dosing strategy for a variety of drugs to improve patient adherence and treatment efficacy. / text