Controlled-release preparation containing metformin hydrochloride and glimepiride and preparation method thereof

Abstract

The invention relates to the field of pharmaceutical preparations, and in particular discloses a compound controlled-release preparation of metformin hydrochloride and glimepiride and a preparation method of the controlled-release preparation. The controlled-release preparation disclosed by the invention consists of an internal controlled-release tablet which contains the metformin hydrochloride and an external drug-loaded coating which contains the glimepiride, wherein the internal controlled-release tablet which contains the metformin hydrochloride comprises a tablet core, an insoluble semipermeable coating film and drug-release small pores. The controlled-release preparation disclosed by the invention can significantly improve the linearity and the uniformity of drug release, the process (the preparation method) is simple and easy to implement, and the tablet is better in compressibility; and the glimepiride, without micronizing treatment or other special treatment, is excellent in dissolving effect.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a compound controlled-release preparation containing glimepiride hydrochloride and metformin and a preparation method thereof. Background technique [0002] Metformin hydrochloride is the first-line drug for the treatment of type II diabetes. It can reduce the production of glycogen, reduce the intestinal absorption of sugar, and improve insulin sensitivity by increasing the uptake and utilization of peripheral sugar without causing hypoglycemia; Meurea is the third-generation sulfonylurea antidiabetic drug, which can inhibit hepatic glucose synthesis, promote the uptake of peripheral glucose by muscle tissue and promote insulin secretion. It has high efficacy and long effect, and only needs to be taken once a day. [0003] Clinical practice has proved that it is difficult to achieve long-term satisfactory control of blood sugar with a single oral hypoglycemic drug. Ut...

AI Technical Summary

Problems solved by technology

However, because the preparation of metformin hydrochloride osmotic pump preparations and the drug-loaded coating of glimepiride have certain difficulties in the specific implementation, and the existing technical solutions have not yet achieved satisfactory technical results

[0010] Tests confirmed that regardless of commercially available Products, or samples prepared in prior art documents (such as US7919116 and CN 101984974.B), the release results under the required test conditions are all unsatisfactory, especially when the drug release rate reaches 60% to 90%. The % interval refers to the middle and late stages of release. Some test products have obvious burst release phenomenon, which also makes their release uniformity have obvious defects.

On the other hand, the above phenomenon shows that when the release rate of this so-called single-component osmotic pump preparation is greater than a certain value (about 60%), the release of the drug is out of control, which is related to the disturbance of the environment, thereby triggering individual The burst release or tablet-to-tablet release rate is not consistent, thus losing the characteristics of traditional osmotic pump preparations against environmental interference

Furthermore, clinical trial evidence shows that the absorption site has a very significant impact on the degree of drug absorption of metformin hydrochloride preparations, so the technical defects of the above preparations may lead to large differences in drug efficacy

[0011] The drug-loaded coating of glimepiride is also a very challenging task: (1) The coating process and time are relatively long (industrial production usually reaches more than 6 hours), and it is in an open or exchange system with the environment, such as Compressed air, hot air, volatile solvents, etc. will all bring about unstable factors in process control; (2) Glimepiride is insoluble in water, methanol, ethanol, acetone, etc., even if Tween 80, twelve Surfactants such as sodium alkyl sulfate are also difficult to obtain the solubility of the coating composition, which increases the difficulty in "uniformity" for the coating of glimepiride with a drug loading of only 1 mg or 2 mg; (3) The insoluble problem of glimepiride also puts forward higher requirements for its rapid dissolution. The patent document WO20060806030 adopts technical solutions such as limiting the particle size of glimepiride, adding surfactants to the coating composition, and coating the isolation coat. However, there is still a large gap between the dissolution data of glimepiride shown and commercially available single composition glimepiride tablets (Yamoli, Glimepiride Tablets)

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