A kind of microsphere preparation method that improves hydrophilic drug encapsulation efficiency

Abstract

The invention discloses a method for preparing microspheres for improving the encapsulation rate of hydrophilic drugs, comprising the following steps: step (a): preparing an internal water phase containing hydrophilic drugs and an oil phase containing a polymer carrier; step ( b): mixing the inner water phase and oil phase to form a primary emulsion, and rapidly cooling down after the primary emulsion is formed to increase the viscosity of the colostrum to 1000-2000cp; step (c): the primary emulsion after the viscosity increase in step (b) is mixed with a volume ratio Mix and disperse in the external water phase at 1:100-1:200 to obtain a double emulsion, and immediately keep the formed double emulsion static for 5-10 minutes to obtain the primary product; step (d): perform the first round of drying on the above-mentioned primary product to obtain a wet For microspheres, the residual organic solvent content of the wet microspheres is not higher than 0.5%, and then a second round of drying is performed to remove water and residual solvents to obtain the final product of microspheres. The invention can obtain polypeptide microspheres with high encapsulation efficiency, high drug loading capacity and extremely low particle size.

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 efficacy. Up to now, there are more than 10 long-acting microsphere varieties 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] Polypeptide and protein drugs play an increasingly important role in the prevention, diagnosis and treatment of diseases due to their high potency, good biocompatibility and low dose. However, such hydrophilic drugs usually have a short half-life in vivo, and need to be administered frequently to 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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