Preparation method of timolol maleate sustained-release microspheres

A technology of timolol maleate and microspheres, applied in the field of medicine, can solve the problems of decreased drug encapsulation rate, long time consumption, low drug loading capacity, etc. Effect

Active Publication Date: 2016-02-17
广州铂思雅生物医药科技有限公司
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  • Abstract
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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.

Method used

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  • Preparation method of timolol maleate sustained-release microspheres

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preparation example Construction

[0026] The preparation method of timolol maleate sustained-release microspheres comprises the following steps:

[0027] 5) Disperse timolol maleate, acrylic resin, Tween, plasticizer, and montmorillonite in an organic solvent, so that the concentration of acrylic resin is 30-100g / L, and the concentration of Tween is 20-60g / L L, the concentration of the plasticizer is 5-20g / L to obtain the inner phase;

[0028] 6) Dissolving Span in vegetable oil to make the concentration of Span 10-40g / L to obtain the external phase;

[0029] 7) Under the stirring state, drop the inner phase into the outer phase to form an oil-in-oil emulsion;

[0030] 8) After the emulsion is ultrasonically treated for 5-30 minutes, the inner phase is evaporated under electromagnetic stirring, washed and dried to obtain sustained-release microspheres.

[0031] The emulsifying agent is very important to the stability of the oil-in-oil emulsion, and the emulsifying agent of the present invention is preferably...

Embodiment 1

[0036] 1) Accurately weigh 30 mg of timolol maleate, 20 mg of sodium montmorillonite, 50 mg of TEC, 50 mg of glycerin, 400 mg of acrylic resin (RSPO:RLPO mass ratio = 2:1), 80-124 mg of Tween, and add them into 5 ml of acetonitrile, Stir to disperse and mix to obtain the inner phase.

[0037] 2) Dissolve 248mg of Span 80 in 10ml of vegetable oil to obtain the external phase.

[0038] 3) At a stirring speed of 600 rpm, 0.3 g of the inner phase was added dropwise to 5 g of the outer phase, and dispersed evenly to obtain an oil-in-oil emulsion.

[0039] 4) Put the emulsion in an ultrasonic cell disintegrator and sonicate for 10 minutes, then evaporate the inner phase with electromagnetic stirring in an ice bath, wash with n-hexane, and dry at room temperature.

Embodiment 2

[0041] 1) Place 500 mg of sodium-based montmorillonite in 5v / v% sulfuric acid, activate it at 90°C for 2 hours, wash until neutral, and dry to obtain modified montmorillonite.

[0042] 2) Accurately weigh 30mg of timolol maleate, 20mg of modified montmorillonite, 50mg of TEC, 50mg of glycerin, 400mg of acrylic resin (RSPO:RLPO mass ratio = 2:1), Tween 80124mg, and add it into 5ml of acetonitrile , stir to disperse and mix to obtain the inner phase.

[0043] 3) Dissolve 248mg of Span 80 in 10ml of vegetable oil to obtain the external phase.

[0044] 4) At a stirring speed of 600 rpm, 0.3 g of the inner phase was added dropwise to 5 g of the outer phase, and dispersed evenly to obtain an oil-in-oil emulsion.

[0045] 5) Put the emulsion in an ultrasonic cell disintegrator and sonicate for 10 minutes, then evaporate the inner phase with electromagnetic stirring in an ice bath, wash with n-hexane, and dry at room temperature.

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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...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/16A61K31/5377A61K47/26A61K47/32A61P27/06
Inventor 侯冬枝刘莉桂茹艺潘育方张兰春胡晟宋凤兰
Owner 广州铂思雅生物医药科技有限公司
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