Study On Glipizide Semisolid-Matrix Sustained-Release Capsules

Semi-solid matrix formulation technology is a new technology by pouring floating semi-solid drug and its carrier into hard gelatin capsules. Compared with other traditional solid formulation technology, Semi-solid matrix formulation technology has lots of advantage such as the flexible and simple formulation ,and the simplest production process-just filling directly after drug and its carrier are mixed.In this paper, Glipizide was selected as model drug and Compritol 888, Gelucires?44/14 and vegetable oil were selected as semi-solid matrix carrier to develop semi-solid sustained-release capsules. In vitro release rate was observed to evaluate the formulation. The mechanism of Glipizide released from sustained-release capsule was investigated. Results indicated that in vitro drug ? release characteristics appeared to be zero-order release, which is erosion mechanism. The effect of Gelucires?44/14, Compritol 888, and Ethocel(100Fp) on release rate was investigated. Results indicated that Gelucires?44/14 increased the release rate; Compritol 888 and Ethocel(100Fp) reduced the release rate. Our preparation's stability was investigated. Results indicated that its released degreee and content were still satisfied after it was stored at r.t. for 9 months.Glipizide is a second-generation oral hypoglycemic agent that belongs to the sulfonylurea class of compounds. Glipizide is widely used in the management of type II (non-insulin-dependent) diabetes mellitus,and delivered orally from 2.5mg to 5mg unequal. Glipizide has a short half-life of 2 to 4 hours,so it is needed frequenctly administration when daily dose exceeds 15mg.This will lead 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 improvepatients' compliance.Glipizide commercial sustained-release tablet was used as control preparation to stud)' the pharmacokinetics and bioavailability of semi-solid sustained-release capsule in dogs. Concentration- time curve was explained by compartment model, which was accorded with oral single-compartment and first-order absorption and first-order elimination. Compared with control preparation, Tmax, MRT ,Cmax and AUC value had not significant difference ,at the level of 0.1. The results indicated that the sustained-release capsules was bioequivalent compared with the control preparation through two one-side test. In vivo absorption percent was worked out with Wagner-Nelson method, and was processed correlation analysis to in vitro release percent (r=0. 8874). There existed good relationship between in vivo and in vitro. Studies showed the self-made capsules could achieve sustained release and bioequivalence in the extent of absorption between self-made capsule and control preparation.