Study Gregor Pyrazine Sustained-release Tablets

Glipizide is a second-generation oral hypoglycemic agent that belongs to the sulfmylurea class of compounds. Glipizide is widely used in the management of typeⅡ（non-insulin-dependent） diabetes mellitus and the elimination half-life 2～4 h. Glipizide delivered orally from 2.5 mg to 5 mg unecaual. Glipizide has a short half-life of 2 to 4 hours, so it is needed frequently administration when daily dose exceeds 15mg. This will lead to the blood-drug concentration vary greatly, and induce toxicity and side-effect easily. So it’s necessary to develop a sustained-release Glipizide formulation with good bioavailability and stability to reduce the frequency of administration and side-effect, and thus improve patients’ compliance.Among different technologies used in controlled drug delivery, hydrophilic matrix systems are the most popular because of the simplicity of formulation, ease of manufacturing, low cost, and applicability to drugs with wide range of solubility. Many polymers are commonly used in hydrophilic matrix formulations including HPMC, Sodium Alginate, Chitosan and Polyvinyl, et al.In this paper, insoluble glipizide was selected as a model drug to study the effect of three different matrix materials HPMC, Kollidon（?）SR and Sodium Alginate on drug release. Sustained release tablets were prepared using the three different polymers as matrix materials. Similarity factors （f₂） between drug release profile of self-prepared tablet and that of reference product were employed as the evaluation standard to optimize the formulation. The results indicated that drug release profile of the optimal formulation were similar to that of reference product. The quality studies on self-prepared sustained release tablets F1 and F2 showed the good release homogeneity, repeatability and less influence on drug release behavior by the in vitro release conditions. The in vitro drug release mechanism was confirmed as the combination result of drug diffusion and matrix erosion. Stress test suggested that self-prepared glipizide was affected slightly by moisture, which meant self-prepared tablets should be preserved sealed. With the commercial glipizide controlled-release tablets as the reference, the in vivo pharmacokinetics of self-prepared glipizide sustained release tablets F1 and F2 was studied with six dogs. Concentration of glipizide in plasma was determined by LC-MS/MS. The pharmacokinetic parameters of the reference tablet were as follows: AUC_0-∞ （ng·h/ml） was 1659.81±943.03, C_max（ng/ml） was 161.07±74.03, T_max（h） was 6.83±2.14. The pharmacokinetic parameters of F1 and F2 were as follows: AUC_0-∞（ng·h/ml） were 1655.51±841.73 and 1879.30±894.55, respectively; C_max （ng/ml） were 157.98±62.30 and 179.82±79.86, individually; T_max（h） were 7.17±1.72 and 6.83±1.33, separately. The relative bioavailability of F1 and F2 were 104.36% and 118.16%, respectively. It was demonstrated that self-prepared sustained released tablet F1 was bioequivalent to reference tablet but the self-prepared sustained tablet F2 was not bioequivalent to reference tablet becauses of the larger AUC and C_max. The two sustain release tablets both have better in vitro-in vivo correlation which was studied by Wagner-Nelson.