Study The Compound Of Metformin Hydrochloride And Gliclazide Osmotic Pump Capsules

Diabetes is a kind of chronic diseases and require lifelong treatment.It cannot effect a radical cure in the current medical level. Diabetes will seriously affect the quality of life of patients and increase burden of heavy economic and health of the patients and the whole society.Therefore the research and development for the treatment of diabete drugs, not only satisfy the requirement of numerous of patients' treatment,but also has very good market prospects. The compound preparation consist of gliclazide and metformin hydrochloride, the mechanism of two drugs complement each other can strengthen the hypoglycemic effect.Metformin hydrochloride and gliclazide compound preparation to avoid the trouble of before the meal and after the meal After the dinner meal and improve patients compliance.Sustained and controlled release drug delivery system have important role in the drug research and development because it can improve patients tolerability and compliance. Controlled release drug delivery system based on osmotic pressure as the drug release power, zero order release for the dynamic characteristic of a new type of preparation. Compared with osmotic pump tablets, osmotic pump capsules have obvious advantages such as: simplify the preparation technology, simplify the process operation, improve the production efficiency; choose flexibility can fill all kinds of drugs; osmotic pump capsules prescription is simple,capsule shell and capsule-core can respectively manufacture, convenient for industrial production.Objective: Study formulationg and preparation technology of compound of metformin hydrochloride and gliclazide osmotic pump capsule prescription and preparation technology of, to build the stable and controllable sustained-release compound of metformin hydrochloride and gliclazide osmotic pump capsule.Methods: Establish the high performance liquid chromatograghy(HPLC) quantitative analysis method for determination metformin hydrochloride and gliclazide in vitro. determination of metformin hydrochloride and gliclazide. Used in adhesive preparation of osmotic pump capsule shells were prepared by dipping glue method,Single factor investigation was investigated metformin hydrochloride medicated layer, gliclazide medicated layer,booster layer,the ingredients of osmotic pump capsule shellsand the number of dipping glue time.The similarity factor f2 was used as as evaluation indexe. The orthogonal design were used to optimize formulation preparation according to the results of single factor investigation and the optimal prescription was verified prescription;A research on the in vitro release condition release effect, and the mechanism of drug release.Explorate release condition in vitro effect the drug release and the mechanism of drug release. To evaluate quality of osmotic pump capsule shells and the preliminary stability of the compound of metformin hydrochloride and gliclazide osmotic pump capsule. Next, the pharmacokinetic experiment of the compound of metformin hydrochloride and gliclazide osmotic pump capsule in Beagle dog was studied.Results:(1)Establish the high performance liquid chromatograghy(HPLC)quantitative analysis method for determination metformin hydrochloride and gliclazide in vitro successfully. In the selected chromatographic conditions, metformin hydrochloride and gliclazide can achieve good separation and peak shape is good, this method can accurate, effective, simple and convenient simple determination the content of metformin hydrochloride and gliclazide.(2) The optimal formulation by the single factor investigation of capsule core is the amount of PVP K90 is 25 mg, the amount of PEO wsr N-80 is 55 mg, the amount of boosting layer PEO wsr-303 is 70 mg, the amount of Na Cl is 35 mg. The prescription and preparation technology osmotic pump capsule shell is the concentration of CA is 8%(W/V), the concentration of PEG6000 is 35%(W/W,acetate fiber proportion), he concentration of TEC is 2%(W/W, acetate fiber proportion), dipping glue three times, natural drying.(3) Appearance of osmotic pump capsules are neat not adhesion, deformation and fracture phenomenon, colour and lustre is uniform, no spots, no abnormal odor. The degree of tightness firmness, friability,weightlessness and so on are meet Chinese pharmacopoeia requirements.The stability of the compound of metformin hydrochloride and gliclazide osmotic pump capsule under high temperature, high humidity and strong light influence is better.(4) In the pharmacokinetic study, compared with market tablets the compound of metformin hydrochloride and gliclazide osmotic pump capsule plasma concentration is smooth and steady, Cmax is lower, the Tmax and MRT were prolonged. It indicated that compared with market tablets the compound of metformin hydrochloride and gliclazide osmotic pump capsule show slow-release properties, extend the action time,there was a slow release.Conclusion: The formulation and preparation technology of the compound of metformin hydrochloride and gliclazide osmotic pump capsule are practicable. The quality of osmotic pump capsule shells are accordance with Chinese pharmacopoeia requirements and the stability is good. Compared with market tablets the compound of metformin hydrochloride and gliclazide osmotic pump capsule have slow release effect and improve the bioavailability.