Preparation method of timolol maleate sustained release microspheres

Abstract

The invention discloses a preparation method of timolol maleate sustained release microspheres. The preparation method comprises the following steps: by adopting an oil-in-oil technology, preparing an internal phase from timolol maleate, modified montmorillonite, acrylic resin, tween and a plasticizer and preparing an external phase from vegetable oil and span; carrying out ultrasonic treatment on an obtained oil-in-oil emulsion; then, electromagnetically stirring to evaporate the internal phase to obtain the timolol maleate sustained release microspheres. The grain diameter of the timolol maleate sustained release microspheres can be controlled in a range of 10 mu m, so that the demand of eye-drops preparations is met. The medicine encapsulation rate reaches up to 80-99%, and the in vitro releasing time can be prolonged to 10-12 hours. The timolol maleate sustained release microspheres prepared by the method serving as an ocular hypotensive agent can reduce intraocular discomfort and reduce the medication frequency, so that the purpose of reducing intraocular pressure for a long time by one-time delivery is realized.

Description

Technical field [0001] The invention belongs to the field of medical technology, and particularly relates to a method for preparing water-soluble intraocular pressure-lowering drug sustained-release microspheres. Background technique [0002] Timolol maleate is a selective β-receptor blocker, which can reduce the production of aqueous humor and significantly reduce intraocular pressure. It has no effect on pupil size, light response and visual acuity. Timolol maleate eye drops are widely used clinically to treat primary open-angle glaucoma and aphakic glaucoma. The efficacy of ophthalmic drugs depends on the effective concentration and residence time of the drug in the cornea. The residence time of traditional eye drops in front of the cornea is 30 seconds, and only 5% of the drug is 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 conjunctiva or canal...

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

Yilmaz Capan 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. The diameter reaches 44.6±2.47μm, the particle size is relatively large and the distribution is uneven

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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