| The purpose of this thesis is to develop innovative dosage forms and formulation design methods based on osmotic pump mechanism for poor water-soluble drugs. The study mainly focuses on some key words-"innovative", "poor water-soluble drugs" and "osmotic pump mechanism". A novel high-density effervescive osmotic pump tablet, a novel gastric-resident asymmetric membrane osmotic pump capsule and a novel formulation prediction system for monolithic osmotic pump tablets were successively designed and developed to popularize the osmotic pump technology, quicken the steps of innovative study of osmotic pump dosage forms at home and abroad, make osmotic pump technology continue to develop and innovate unceasingly, and to overcome the deficiencies of existing technologies, achieve more extensive and diverse effects and maximize the potential. This study is also expected to throw out a minnow to catch a whale to absorb advanced and high technology elements into pharmaceutics and dedicate our strength to the development of pharmaceutics as well as pharmacy.Two important parameters of polyethylene oxide—intrinsic viscosity and water uptake were systematically determined for further study. Ubbelohde viscometer was used for intrinsic viscosity determination. The innovation of sponge method was applied for water uptake determination to avoid polymer dissolving and errors cased by contact with other medium.A novel high-density effervescive osmotic pump tablet was studied. The innovation is the addition of pharmaceutical iron powder into core tablet. On the one hand, the pharmaceutical iron powder reacts with the gastric fluid flowing into the core tablet to generate gas which forces water-insoluble drug suspension outwards completely. On the other hand, the presence of the pharmaceutical iron powder increases the system density to over 2.5 g·cm-3. The system will sink to the bottom of the stomach, which will prolong the drug delivery time in absorption zone and improving the bioavailability. Gamma scintigraphy was selected as the method to monitor gastric residence time of the radio-labeled systems in Beagle dogs.A novel gastric-resident asymmetric membrane osmotic pump capsule was studied. The innovation is that drug, polyethylene oxide and osmotic agent are filled directly into the capsule in the form of powders. Because the bulk density of powders is quite low for the high porosity, the whole system is approximately hollow. Therefore, during controlled drug delivery in the driving force of osmotic pressure, this capsule will be floating on the medium, which will prolong the drug delivery time in absorption zone and improving the bioavailability. The bioavailability study in Beagle dogs was carried out to compare test preparation and reference preparation.A novel formulation prediction system for monolithic osmotic pump tablets was designed. The innovation is to bring forward a new method to evaluate formulations—ternary-component diagram. Based on over 7000 original data and more than 400 formulations, a triangular prism model was established. Formulation prediction system was finally programmed by MATLAB(?) software. The prediction ability of the system was evaluated and approved:the optimal formulation region can be immediately obtained after entering the information of some poor water-soluble drug and polyethylene oxide. Therefore the experiment efficiency will be improved and R & D period will be shortened. |
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