A microsphere that overcomes stagnation and releases hydrophobic drugs at a constant rate and its preparation method

Abstract

The invention provides a microsphere capable of overcoming the stagnation phase and releasing hydrophobic drugs at a constant speed, and a preparation method thereof. The preparation method comprises the following steps: (1) dissolving hydrophobic drugs and a polymer material into an organic solvent to obtain a solution (A); (2) mixing the solution (A) obtained in the step (1) with an inner water phase, and carrying out an emulsification treatment to obtain primary emulsion, wherein the volume ratio of the inner water phase to the solution (A) is 1:5-66.7; (3) adding the primary emulsion obtained in the step (2) into a surfactant water solution with a concentration of 0.005 to 0.05 g / mL, carrying out an emulsification treatment to obtain multiple emulsion, and stirring until emulsion drops are cured or the organic solvent is completely volatilized; and (4) drying the particles obtained in the step (3) to obtain the microsphere. The provided microsphere has a quick effect, the content of residual organic solvent in the microsphere is 600 ppm or less; and other auxiliary materials are not needed.

Description

technical field [0001] The invention belongs to the field of controlled-release preparations of hydrophobic drugs, in particular to a method for preparing microspheres that overcome stagnation and release hydrophobic drugs at a constant rate. Background technique [0002] The outstanding feature of sustained-release preparations is that they can continuously release effective doses of active ingredients for a long period of time after one dose of medication. Based on this feature, this type of preparation is especially suitable for chronic diseases that require long-term medication, such as diabetes, schizophrenia, etc. , especially for drugs with short half-lives that require frequent administration in conventional dosage forms, it can significantly improve patient compliance; in addition, the blood concentration of such preparations changes little in the body, which can avoid toxic and side effects beyond the therapeutic range, and can also be kept within the therapeutic wi...

AI Technical Summary

Problems solved by technology

In Chinese patent CN103462901, after the microspheres are solidified, ethanol is used as a bridge solvent for cleaning, which can reduce the methylene chloride content in the final product to 600ppm; but adding ethanol cleaning steps in an aseptic production environment undoubtedly increases the risk of bacterial contamination Risk and complexity of operation, and the residue of bridge solvent ethanol also needs to be strictly controlled in the final product

However, simply relying on increasing the final temperature of the analysis and drying stage and prolonging the freeze-drying time to make the organic solvent below 600ppm sometimes does not work, and these two methods not only waste power energy, but also may affect the stability of the active ingredient for temperature-sensitive samples. , when the analytical drying temperature is higher than the polymer material T g It is also easy to cause microsphere adhesion phenomenon

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