Metformin-pioglitazone salt, and preparation method and application thereof

Abstract

The invention relates to a metformin-pioglitazone salt, and a preparation method and an application thereof. The preparation method comprises the following steps: dissolving pioglitazone and metforminraw materials in a single solvent or a mixed solvent according to a molar ratio of 1:0.8 to 1:1.2; reacting and crystallizing the obtained mixture at 15-60 DEG C for 12-48 h; carrying out solid-liquid phase separation on the obtained product, and performing drying at 25-60 DEG C to obtain a solid sample of the metformin-pioglitazone salt. The metformin-pioglitazone salt provided by the inventionhas a greatly higher hygroscopic stability than the metformin product: the hydroscopic weight gain of the salt at a relative humidity of 95% is 33%, and the hydroscopic weight gain of the metformin single product under the same condition is 86%; the solubility of the metformin-pioglitazone salt in pure water is 1824 [mu]g/ml, and the solubility of the pioglitazone single product in the pure wateris less than 1 [mu]g/ml; and the preparation method of the salt has the advantages of simplicity in operation, easiness in control of the crystallization process, and good reproducibility of the salt.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and in particular relates to metformin-pioglitazone salt in crystal form, its preparation method, pharmaceutical composition and application. Background technique [0002] According to statistics, about 70-80% of drug candidates fail to be marketed due to defects in physical and chemical properties. Therefore, improving the physical and chemical properties of drugs is of great significance for the development of new drugs. In the preclinical research and development stage of drugs, new drug R&D companies usually use the active ingredients of drugs to form salts to improve the drug's solubility, dissolution rate, hygroscopicity, stability and bioavailability and other pharmaceutical properties. In the first half of 2017, the U.S. Food and Drug Administration (FDA) approved a total of 23 new drugs, including 16 new molecular entities and 7 new biological products. Among the 16 chemical...

AI Technical Summary

Problems solved by technology

However, pioglitazone is a class II drug (BCS II) in the biopharmaceutical classification system, which has low solubility, so its pharmaceutical properties are not good

[0004] Metformin (C 4 h 11 N 5 ) is a biguanide oral hypoglycemic agent for anti-type 2 diabetes. It is different from pioglitazone, mainly increasing anaerobic glycolysis and utilization of glucose, increasing glucose oxidation and metabolism in skeletal muscle and adipose tissue, and reducing intestinal absorption of glucose , while inhibiting the production and output of glycogen and improving insulin resistance, but metformin is unstable and easily absorbs moisture, which is not conducive to the storage and transportation of drugs, so its hydrochloride form is common

However, the problems of these two drugs are still unavoidable

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