Bosentan sustained-release matrix tablet and preparation method thereof

Abstract

The invention discloses a bosentan sustained-release matrix tablet and a preparation method thereof, which are characterized in that bosentan is adopted as an active ingredient, auxiliary materials such as sustained-release matrix materials, fillers, lubricants, pH adjusting agents, moistening agents and the like are added, and a wet pelleting technology or a dry direct tabletting technology is adopted, so that a gel sustained-release matrix tablet is prepared. Experimental results show that the prepared sustained-release tablet is slowly and durably released both inside and outside a human body, and a good biological availability inside the human body can be realized.

Description

Technical field [0001] The invention relates to a new preparation of bosentan, in particular to a matrix sustained-release tablet containing bosentan active ingredients and a preparation method thereof, and belongs to the field of medicine. Background technique [0002] Bosentan (Bosentan), the chemical name is N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyrimidin-2-yl-pyrimidin-4-yl ]-4-tert-butylbenzenesulfonamide, a dual endothelin receptor antagonist, has affinity for ETA and ETB receptors, and is clinically used to treat patients with WHO stage III and IV primary pulmonary hypertension Pulmonary hypertension, or pulmonary hypertension caused by scleroderma. [0003] Bosentan has poor water solubility and is easily affected by pH. The lower the pH, the worse the solubility. When pH=7.5, the water solubility is the largest, about 43mg / 100ml. The absolute bioavailability of bosentan is about 50% and it is not affected by food. The maximum plasma concentration is reached 3-5 ...

AI Technical Summary

Problems solved by technology

However, its elimination half-life is short, about 5 hours. In order to achieve the best therapeutic effect, the drug needs to be taken 2 to 3 times a day, resulting in large fluctuations in the plasma drug concentration of patients, resulting in the possibility of "peak-valley" phenomenon

When the blood concentration is high, it may cause side effects or even poisoning; when it is low, it may be below the therapeutically effective concentration, so that it cannot show curative effect

[0005] In the prior art, the patent document CN101175484 discloses a dispersible bosentan tablet, which utilizes the rapid disintegration of the dispersible tablet to increase the in vivo absorption of bosentan and improve the bioavailability; the patent document CN102114005A discloses A bosentan capsule was developed, and the method utilized solid dispersion technology to increase the dissolution and release of bosentan drugs, but the above two methods did not solve the need for multiple doses due to the short half-life of the drug, and the possible occurrence of blood drug "Peak and valley" phenomenon caused by large concentration fluctuations

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