Study On Preparation And Properties Of Compound GLIPIZIDE Sustained-release Capsules

In this thesis, glipizide pellets and Metformin Hydrochloride pelletswere prepared by centrifugal granulation process and sustained-releasepellets of Metformin Hydrochloride were prepared by coating withsustained-release materials. Compound sustained-release capsules ofglipizide were made up glipizide pellets and sustained-release pellets ofMetformin Hydrochloride by the proportion of prescriptions.The preparationmethods for Compound sustained-release capsules of glipizide and influencefactors involved, stability, pharmacokinetics and bioavailability oncompound sustained-release capsules were studied completely and thoroughly.Results show: the pellets of compound sustained–release capsules had goodappearance and stability, the sustained-release property ofsustained–release capsules was marked.Firstly,the proportion of the drugs of sustained–released capsule andall kinds of adjuvants and the preparation process of common released pelletswere studied completely and thoroughly.Blank pellet core were prepared byMCC(loading agent) and water(bonding agent); MCC and galactosylglucose werediluting agent of Metformin Hydrochloride and glipizide; bonding agent were5%aqueous solution of Hydroxypropylmethylcellulose; then common releasedpellets were prepared by stratification method. Glipizide common pellets andMetformin Hydrochloride common pellets were prepared by centrifugalgranulation process with Multifunction centrifugal granulation coatingmachine. Furthermore, the prescription and prepared process were studiedcompletely. The pellets had good appearance and stability.Secondly,aqueous solution（Eudragit NE30Dand Eudragit L30D55）was used assustained-released membrane material. The effects of process variables andformulation variables on pellets preparation were investigated. Theformulation and technology of sustained-release pellets of MetforminHydrochloride were optimized. The sustained-released pellets had obvioussustained-release characteristics, the drug release profile in vitro followed first order kinetics. Compound sustained-release capsules ofglipizide were made up common released pellets of glipizide andsustained-release pellets of Metformin Hydrochloride with prescriptionproportion. Glipizide of Compound sustained-release capsules of glipizidecould dissolute in vitro and content uniformity of it was ideal. In thisprocess, the instrument was operated easily, the technology was simple, allkinds accessories were get easily, low price. Moreover, Compoundsustained-release capsules of glipizide comply with rule of CPH.In the thesis, Ultraviolet spectrophotometry method was developed forassaying content and drug release of Metformin Hydrochloride of compoundsustained-release capsules of glipizide. High performance liquidchromatography method was developed to determine content, content uniformityand dissolution of glipizide. The two kinds of methods were simple, accurate.By technology test,the two determination methods were applicable to determinein vitro.In this thesis, the fit factors method was used to study the stabilityof compound sustained-release capsule. Result show: The drug content ofsustained-release capsules and dissolution of glipizide and MetforminHydrochloride were stability. Then, the drug content and release stabilityof the capsule were both good under high temperature, high humidity andintensive light test.Lastly, Pharmacokinetics and bioavailability studies of compoundsustained-release capsule and Metformin Hydrochloride sustained–releasepellets were performed based on determination of plasma concentration ofdrugs in dogs at different intervals after a single oral administration. Theplasma concentration of Metformin Hydrochloride sustained–release pelletswere stability, extending the time to peak, lower peak concentration, therelative bioavailability of Metformin Hydrochloride was98.48%compared withcommon-release pellets. Obvious correlation existed between absorptionfraction in vivo and the release percentage in vitro.