Water-soluble drug sustained-release microsphere and preparation method and applications thereof

Abstract

The invention discloses a water-soluble drug sustained-release microsphere and a preparation method and applications thereof. The microsphere comprises an inner core area and an outer core dispersing area; the inner core area is formed by using an isolating oil phase to seal the water-soluble drug; the outer core dispersing area is a medical macromolecular accessory. The invention discloses the preparation method for the water-soluble drug sustained-release microsphere; the medical macromolecular accessory is dissolved into an organic solvent to form a dispersing medium; the powder of the water-soluble drug is dispersed into an isolating layer oil phase to form suspension liquid and slowly release into the dispersing medium; then the suspension liquid is prepared into first milk; then thefirst milk is prepared into emulsion. The organic solvent is volatilized to form the microsphere; the suspension liquid dispersed with the microsphere is centrifugated, filtered, washed, dried and collected, thus obtaining the microsphere. The invention also discloses an emulsion-solvent vaporizing method to prepare the water-soluble drug sustained-release microsphere and the applications of the preparation method in different drug preparations. The microsphere preparation technique is stable, and practical; the shape of the microsphere is round; the surface is smooth, the fluidity is good and the granularity distribution is uniform.

Description

technical field [0001] The invention relates to a water-soluble drug slow-release microsphere, a preparation method and application thereof, and belongs to the field of pharmaceutical preparations in medical engineering. Background technique [0002] Microsphere (microsphere) refers to the particle dispersion system formed by drug dispersion or adsorption in polymer or polymer matrix. According to different carrier materials for the preparation of microspheres, they are mainly divided into natural polymer microspheres (such as starch microspheres, albumin microspheres, gelatin microspheres, chitosan, etc.) and synthetic polymer microspheres (such as polylactic acid microspheres) . [0003] Since the 1970s, many countries have begun to study the preparation methods of various drug-loaded microspheres and apply them to embed various forms of drugs. Although such microsphere formulations provide a sustained drug release form, there are still some disadvantages. A major probl...

AI Technical Summary

Problems solved by technology

The second problem is that a big disadvantage of the traditional microsphere preparation method is that the encapsulation efficiency of water-soluble drugs is extremely low

This not only reduces the encapsulation efficiency of the drug, but also leaves many porous channels on the surface of the microspheres, which affects the release of the microspheres in vitro

The third problem is the instability of the drug when it is in contact with organic solvents for a long time under the severe conditions of preparing microspheres, such as high temperature or solvent evaporation.

The fourth problem is that none of these microsphere dosage forms can provide a constant rate release pattern, that is, a zero-order release pattern

For non-erodible materials, since the drug diffusion channel cannot be maintained throughout the release period, the drug release rate is inconsistent; for erodible materials, the surface area of ​​microspheres is constantly changing during the release process, and the dispersed Drug release rate can not be constant

[0004] There are currently three methods for preparing water-soluble drug microspheres. The first method is the oil-in-water (O / W) emulsification solvent evaporation method. However, when preparing water-soluble drug sustained-release microspheres by this method, due to the water solubility of the drug, A large amount of loss during the preparation process, the drug encapsulation efficiency is very low

The second method is the oil-in-oil (O / O) emulsified solvent evaporation method. Although the microspheres with high encapsulation efficiency and drug loading capacity are obtained, the burst release phenomenon of the microspheres is obvious, and the release time in vitro is relatively short. no sustained release effect

However, when preparing W / O / W emulsion, the emulsion may have oil film rupture, internal water phase aggregation and other reasons to reduce the encapsulation efficiency of the drug

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