| In this paper, insoluble glipizide was as the model drug to prepare the bi-layer osmotic pump tablets and cyclodextrin complex osmotic pump tablets. Furthermore, drug release behavior and mechanism of two types of controlled release tablets were deeply studied.Until now, reports about formulation and arts of bi-layer osmotic pump still were not beheld in China. Documents that were found out were almost patents, where whole messages about arts and formulation were difficultly got. Therefore, in this paper glipizide as the model drug, was prepared the bi-layer osmotic pump controlled release tablets with polyethylene oxide (PEO) as the main excipients of the tablet core. The effects of many factors including formulation of drug layer, push layer and membrane, arts of tablet and the condition of drug release on the release behavior of controlled release tablets were investigated. After comprehensive pre-formulation research, amount of sodium chloride, polyox 303, HPMC in push layer and weight of membrane were selected as the causal factors. And similarity factors (f2) between drug release profile of self-preparing tablets and imported product (Glucotrol XL, Pfizer) were used as the evaluation standard to optimize the formulation according to orthogonal experiment design. The results indicated that drug release profiles of the optimal formulation were similar to that of imported product, and from 2 to 16 hours they had the excellent zero-order release character in vitro (r =0.9989, F16>75%). In addition, the results of stability experiments indicated that this product was sensitive to humidity. Exposed on the conditions of RH 92.5% after 5 days, something like grume effused from the orifice. But under light, heat and accelerating conditions, the product was stable.In the paper, for the first times drag release mechanism of bi-layer osmotic pump was deeply illustrated from rheology of suspension and expansibility of polymer. Parameters such as flow index (n), consistency coefficient (K) and viscosity-flow activation energy (E) of drug layer suspension, swelling ratio (Q), swelling rate constant (Ks), Ks activation energy of push layer (Ea), drug release rate activation energy (Ek), tensile strength (a) and elastic modulus of membrane (E) were calculated. Phenomenon during drug release such as minimum orifice, effect of temperature on drug release rate, and time lag were also rationally interpreted. After determining rheology and expansibility of various polymers, fitting materials were selected to design a new tablet core of bi-layer osmotic pump. Results of drug release in vitro indicated that the new formulation had well zero order release character from2 to 16 hours. And it had similar drug release behavior with the formulation using PEO. But compared to the formulation using PEO, drug release behavior of the new formulation was less affected by temperature.To make insoluble drug into osmotic pump controlled release tablets with simple and effective methods, in the paper a new kind of osmotic pump with P-cyclodextrin as complex material was designed. Here, glipizide was as the model drug again. The effects of the osmotic promoting agent, various cyclodextrin, arts of preparing complex, coating composition, coating thickness and the dissolution medium on the drug release behavior were investigated. Weight of coating and amount of P-cyclodextrin were selected as the causal factors according to multiple factorial experiment design. The correlation coefficient of the accumulative drug release amount and the time (r) from 2 to 14 hours and F14, which represent the in vitro drug release percent in 14 hours were used as the evaluation standard to optimize the formulation. The drug release mechanism of the optimal formulation was also investigated. The results indicated that the optimal formulation had zero order release character and the drug release was mainly modulated by the osmotic pressure difference between the dissolution medium and the solution inside the coating. In addition, equation of kinetics...
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