Preparation method of microspheres capable of increasing entrapment efficiency of hydrophilic medicines

Abstract

The invention discloses a preparation method of microspheres capable of increasing entrapment efficiency of hydrophilic medicines. The preparation method comprises the following steps: step (a): preparing an inner water phase containing hydrophilic medicines, and an oil phase containing polymer carriers; step (b): mixing the inner water phase with the oil phase to obtain primary emulsion, and after formation of the primary emulsion, performing fast temperature reduction to increase stickiness of primary emulsion to 1000-2000cp; step (c): mixing and dispersing the primary emulsion after stickiness increase in the step (b) in a volume ratio being (1:100)-(1:200) in an outer water phase to obtain secondary emulsion, and immediately maintaining the formed secondary emulsion static for 5-10minso as to obtain primary products; and step (d): performing first-round drying on the primary products to obtain humid microspheres, wherein the residual quantity of organic solvents in the obtained humid microspheres is not higher than 0.5%, and then performing second-round drying to remove moisture and remaining solvents so as to obtain microsphere end products. Through the adoption of the preparation method, the polypeptide microspheres high in entrapment efficiency, high in medicine loading quantity and low in grain size can be obtained.

Description

technical field [0001] The invention relates to the technical field of microsphere preparation, in particular to a microsphere preparation method for improving the encapsulation rate of hydrophilic drugs. Background technique [0002] Compared with traditional preparations, long-acting sustained-release preparations can reduce the number of administrations, improve patient compliance, reduce side effects, and improve curative effect. It has highlighted clinical advantages and has become a hot spot in the development of new drug dosage forms in recent years. Up to now, there are more than 10 long-acting varieties of microspheres on the market in foreign countries. Except for risperidone, naltrexone, and minocycline hydrochloride, the rest are hydrophilic drug molecules, including peptide and protein drugs. [0003] Peptide protein drugs play an increasingly important role in the prevention, diagnosis and treatment of diseases due to their high potency, good biocompatibility a...

AI Technical Summary

Problems solved by technology

These methods are effective, but too high oil phase concentration and internal water phase concentration will make it difficult to filter and sterilize in industrial production, and too high colostrum viscosity will cause increased transfer loss and sacrifice yield. Industrialization brings new difficulties

[0009] The inventor found in the long-term product development work that when the viscosity of colostrum is increased to about 2000cp, the encapsulation efficiency can be improved from 60 to 70% (conventional double emulsion method) to 85 to 90%, but there is More serious drug loss phenomenon; when the viscosity of colostrum is continued to be increased to 2000-5000cp or even higher, the encapsulation rate will be further increased to 90-95% at this time, but the dispersion process of colostrum is hindered in this high-viscosity state, Before the complex emulsion droplet is sheared to form a round sphere, the polymer material on the surface is precipitated and solidified to form, which often results in uneven particle size and irregular shape of the microspheres, showing the coexistence of various shapes such as filamentous, olive-shaped, and tadpole-shaped , reduce clinical drug administration and increase injection difficulty

These irregularly shaped microspheres will also form a bridging effect during the centrifuge collection process, resulting in incomplete solid-liquid separation, loose microsphere precipitation, and turbid supernatant, which will bring Take a lot of microspheres, resulting in a drop in yield

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