The Study Of Controlled-Release Osmotic Pump Tablets Of Insoluble Vinpocetine

In this paper, vinpocetine was selected as the model drug to prepare push-pull osmotic pump controlled-release tablets andβ-cyclodextrin polymer complexing micro-porous osmotic pump controlled-release tablets. Then, the pharmacokinetic study of push-pull osmotic pump controlled-release tablets was performed in six beagle dogs.In the preparation of vinpocetine push-pull osmotic pump tablets, polyethylene oxide （PEO） HPMC and sodium chloride were used as the tablet core. Cellulose acetate （CA） and polyethylene glycol 4000 （PEG 4000） were employed as the coating materials, acetone was selected as the coating medium. The effects of many factors including composition of tablet core and coating membrane, arts of preparing tablet and the condition of drug release on the in vitro release behavior of push-pull osmotic pump tablets were investigated. Based on the single-factor experiments, the amount of HPMC, PEO and NaCl, the weight of coating were selected as the causal factors. The formulation optimized according to four factors and three levels orthogonal experiment design was proved to have the excellent zero-order release character and reproducibility of different batchesA novel water-solubleβ-cyclodextrin polymer complexing micro-porous osmotic pump tablet for vinpocetine delivery was designed. Different varieties and quantity of osmotic promoting agents, different amount of plasticizer and pore former, different arts of complexing preparation, coating composition, coating thickness and the dissolution medium on the drug release behavior were also investigated. Based on factor-screening experiments, an optimal formulation was decided which amount of plasticizer and pore former selected as the causal factors according to multiple factorial experiment design, and a well zero-order release character up to 12h was achieved.With the commercial product as the reference, the relative bioavailability and pharmacokinetic study of vinpocetine push-pull osmotic pump tablets were performed in six Beagle dogs. With crossover design, HPLC method was employed to detect the drug concentration in plasma of dogs after administered with single dose. The pharmacokinetic parameters of the test and reference tablets were as follows: AUC （ng·h/l） were 2164.15± 293.20 and 2049.38±308.786, C_max（ng/l） were 108.64±33.94 and 276.97±33.94,t_max（h） were 4.50±1.10 and 4.10±0.65.The relative bioavailability was 105.6%. Bioequivalent judgement indicated that these two dosage forms were bioequivalent. The results of judgement showed that the in vitro release of self-made push-pull osmotic pump was correlative well with absorption fraction in vivo （r=0.9763）.