A kind of tadalafil enteric-coated tablet and preparation method thereof

Abstract

The invention provides tadalafil enteric-coated tablets. The enteric-coated tablets consist of a tablet core and an enteric coating. The tablet core is prepared from raw and auxiliary materials listedin the following list, the main drug tadalafil is pre-crushed until the particle size D90 is 5-50 microns and is mixed with a diluent with a particle size D90 of 50 microns or below to form a composition, and various auxiliary materials are sieved by a 60-100-mesh sieve in advance. The enteric coating is prepared from one or more of cellulose acetate phthalate, polyacrylic resin and an enteric formula. The invention provides a preparation method of the tadalafil enteric-coated tablets. Through the repeated grinding, sieving and mixing of the crushed tadalafil and the diluent, the step-by-steppremixing and the particle size control of the raw and auxiliary materials, the problem of the mixing uniformity of the particles is well solved. The bioavailability of the medicament is effectivelyimproved, a delayed release effect is provided, and the tablets enable patients to be more durable, and are suitable for the treatment of erectile dysfunction and premature ejaculation.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a preparation method of tadalafil enteric-coated tablets. Background technique [0002] Tadalafil (CAS: 171596-29-5) is a novel oral reversible selective inhibitor of phosphodiesterase 5 (PDE5). The molecular formula of tadalafil is C 22 h 19 N 3 o 4 , the molecular weight is 389.41. Tadalafil is practically insoluble in water, slightly soluble in ethanol, and soluble in DMSO. The properties are white crystals, non-hygroscopic, and the melting point is 302°C. Developed by Eli Lilly and Company, from 2009 to 2011, FDA approved it for the treatment of erectile dysfunction, pulmonary arterial hypertension (PAH) and benign prostatic hyperplasia (BPH). [0003] It is mentioned in the patent CN101500572A, and it is reported in US Patent No. 6841167 that the solubility of tadalafil in water at 25°C is about 2 μg / ml, that is, it is almost insoluble in water. ...

AI Technical Summary

Problems solved by technology

[0004] Because of the shortcoming of tadalafil's poor water solubility, its particle size needs to be reduced. The current common practice is to reduce its particle size to below 10 μm or even lower, which creates a new problem, whether it is wet granulation or not process, in the mixing stage of the preparation process, the particle size of the imported or domestic excipients used is difficult to match with such a small particle size raw material

The particle size of excipients is too large to easily lead to uneven mixing, so that the content uniformity of the preparation product becomes poor

[0005] The tadalafil preparations currently on the market are all ordinary tablets, which have problems such as short residence time of the drug in the body after taking the drug, uneven absorption and distribution, low bioavailability, many adverse reactions, and insignificant curative effect.

[0006] The inventor has found through a large number of experiments that tadalafil is unstable and easily degradable in strong acids (such as 0.1mol / L hydrochloric acid aqueous solution)

Therefore, after the ordinary tablet is taken, tadalafil is destroyed by gastric juice in the stomach, thereby reducing the drug effect and resulting in low bioavailability

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