Preparation method of timolol maleate sustained-release microspheres

Abstract

The invention discloses a preparation method of timolol maleate slow-release microspheres. The present invention adopts oil-in-oil technology, prepares inner phase with timolol maleate, modified montmorillonite, acrylic resin, Tween, and plasticizer, prepares outer phase with vegetable oil and Span, and the obtained oil-in-oil After the emulsion is ultrasonically treated, the internal phase is evaporated by electromagnetic stirring to obtain timolol maleate sustained-release microspheres, whose particle size can be controlled within the range of 10 μm, which meets the requirements of ophthalmic preparations. Its drug encapsulation rate is as high as 80-99%, and the release time in vitro can be extended to 10-12 hours. The timolol maleate sustained-release microspheres prepared by the method are used as an intraocular pressure-lowering drug, which can reduce discomfort in the eye, reduce the number of medications, and realize the purpose of lowering the intraocular pressure for a long time by one administration.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation method of water-soluble intraocular pressure-lowering drug slow-release microspheres. Background technique [0002] Timolol maleate (timololmaleate) is a selective β-receptor blocker, which can reduce the formation of aqueous humor and significantly reduce intraocular pressure, and has no effect on pupil size, light response and vision. Timolol maleate eye drops are widely used clinically in the treatment of primary open-angle glaucoma and aphakic glaucoma. The efficacy of ophthalmic drugs depends on the effective concentration and residence time of the drugs in the cornea. The residence time of traditional eye drops in front of the cornea is 30s, and only 5% of the drugs are absorbed by the cornea. Frequent administration is required, and the dosage of eye drops is difficult to control , and most of them enter the blood circulation through the conjunc...

AI Technical Summary

Problems solved by technology

[0005] The method of preparing microspheres can be divided into single emulsion (O / W type, W / O type, O / O type)-drying method in liquid and There are two types of double emulsion (W / O / W type and O / W / O type)-in-liquid drying method: (1) Single emulsion (O / W)-in-liquid drying method is a common method for hydrophobic drug microspheres , the disadvantage of this method is that the surface of the prepared microspheres is often embedded with drug crystals. In addition, this method is not suitable for encapsulating more water-soluble drugs, because the drugs are easily distributed from the oil-water interface during the process of emulsification and in-liquid drying. The encapsulation efficiency of the drug decreased significantly in the external aqueous phase

(2) Double emulsion (W / O / W)-liquid evaporation method, which takes a long time, is not easy to control, and has low yield

YilmazCapan et al. used the W / O / W-solvent evaporation method to prepare polylactide-glycolide microspheres loaded with water-soluble protein-human growth hormone. The surface of the microspheres prepared by this method was not round enough and had holes, and the average particle size Up to 44.6±2.47μm, relatively large particle size and uneven distribution

Moreover, the drug loading capacity of water-soluble drugs is relatively low due to the easy diffusion from the inner aqueous phase to the outer aqueous phase.

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