CN-121987583-A - Candesartan cilexetil capsule and preparation method thereof

CN121987583ACN 121987583 ACN121987583 ACN 121987583ACN-121987583-A

Abstract

The invention provides a candesartan cilexetil capsule and a preparation method thereof, and the candesartan cilexetil capsule is characterized in that each capsule contains candesartan cilexetil, lactose, corn starch, hydroxypropyl cellulose, carboxymethylcellulose calcium, polyethylene glycol 8000 and magnesium stearate. The candesartan cilexetil capsule provided by the invention solves the problem of candesartan cilexetil stability, reduces the possibility of crystal transformation of a common tablet in the tabletting process, has similar characteristic dissolution curves of a final product and a reference preparation, has a simple preparation method and process route, is less in loss by a fluidized bed one-step granulating method, has higher product yield, and reduces industrial mass production cost.

Inventors

Lin chuangsheng
Lai Lijie
ZHANG ZHIGANG
Liao Jieyu
XIE BIN
LING YUFENG

Assignees

珠海润都制药股份有限公司

Dates

Publication Date: 20260508
Application Date: 20241106

Claims (2)

1. The candesartan cilexetil capsule is characterized in that each capsule consists of, by weight, 5-6% of candesartan cilexetil, 70-72% of lactose, 14-15% of corn starch, 4-5% of hydroxypropyl cellulose, 1-2% of carboxymethylcellulose calcium, 1-2% of polyethylene glycol 8000 and 0.3-0.5% of magnesium stearate.
2. A process for preparing candesartan cilexetil capsule according to claim 1 comprising the steps of: (a) Preparing and treating raw and auxiliary materials, namely weighing candesartan cilexetil, lactose, corn starch, polyethylene glycol 8000, hydroxypropyl cellulose, carboxymethylcellulose calcium and magnesium stearate with prescription amount for later use; (b) Preparing adhesive, namely weighing the prescription dose of hydroxypropyl cellulose, adding the hydroxypropyl cellulose into purified water, and preparing a clear and transparent solution with the concentration of 5 percent for standby; (c) Granulating in one step by using a fluidized bed, namely putting the candesartan cilexetil, lactose, corn starch and polyethylene glycol 8000 weighed in the step (a) into a fluidized drying granulator, starting a fan with the frequency of 5-50 Hz, setting the air inlet temperature to 40-60 ℃, controlling the material temperature to be less than or equal to 50 ℃, starting spraying liquid, spraying the prepared adhesive, and granulating in one step at the liquid supply speed of 50-150 rpm to finally obtain granules with the moisture of less than or equal to 3.5 percent for later use; (d) Finishing, namely putting the dry particles obtained in the step (c) into a pulverizer, and finishing the particles by using a screen with the screen aperture of 0.1mm to obtain finished particles with certain particle size distribution for later use; (e) Adding the granules obtained in the step (d) and the prescription amount of carboxymethylcellulose calcium into a butt-clamp square cone mixer, setting the mixing rotating speed to be 10rpm, mixing for 10min, adding the weighed magnesium stearate, and continuing mixing for 5min to obtain total mixed granules for later use; (f) And (3) filling the capsule, namely filling the total mixed particles obtained in the step (e) into a gelatin hollow capsule by using a full-automatic hard capsule filling machine to obtain the candesartan cilexetil capsule.

Description

Candesartan cilexetil capsule and preparation method thereof Technical Field The invention relates to a candesartan cilexetil pharmaceutical preparation, in particular to a candesartan cilexetil capsule which has a simple process and can be dissolved out similarly to a reference preparation and a preparation method thereof. Background Candesartan cilexetil is developed by the Japanese Takeda company and is a prodrug of Candesartan, which can be completely hydrolyzed and converted into active Candesartan in the gastrointestinal tract absorption process, and the latter is a novel angiotensin II receptor subtype AT1 antagonist which can specifically act on the AT1 receptor. The former candesartan cilexetil tablet was marketed in the united kingdom 4 months 1997, and is clinically used for treating circulatory diseases such as hypertension, heart disease (heart attack, heart failure), cerebral apoplexy, nephritis, etc., and is marketed in the united states after approval by the FDA 1998, and the trade name is Atacand, and candesartan cilexetil tablet "Blopress (bitoros)" produced by the japan martial medicine industry co. At present, candesartan cilexetil tablets are marketed in more than 70 countries worldwide, and improvements on candesartan cilexetil formulations are continuously underway. The patent CN101623275A discloses a capsule containing candesartan cilexetil and a preparation method thereof, wherein the capsule content of the capsule contains active ingredient candesartan cilexetil, oily compound with low melting point, at least one disintegrating agent and at least one lubricant, and the capsule shell of the capsule is hydroxypropyl methyl cellulose capsule shell. In the prior art, the research on candesartan cilexetil preparation is focused on the improvement of the original candesartan cilexetil tablet, the improvement of a few dosage forms is changed into a capsule on the basis of the tablet prescription, the general dosage form of candesartan cilexetil in the market is a tablet, the process is wet granulation and total mixed tabletting after fluidized bed drying, the high-speed running extrusion of tabletting process equipment of the tablet can possibly cause the candesartan cilexetil to carry out crystal transformation, the stability of the medicine is influenced, the candesartan cilexetil capsule in the scheme is filled in the capsule after fluidized bed one-step granulation, the process steps are simpler, the production efficiency is higher, the extrusion degree of materials is greatly reduced, the crystal form stability of the candesartan cilexetil can be better maintained, and the stability and the effectiveness of the medicine are further ensured. Disclosure of Invention The invention provides candesartan cilexetil capsules and a preparation method thereof, wherein each capsule consists of 5-6% of candesartan cilexetil, 70-72% of lactose, 14-15% of corn starch, 4-5% of hydroxypropyl cellulose, 1-2% of carboxymethylcellulose calcium, 8000-2% of polyethylene glycol and 0.3-0.5% of magnesium stearate in percentage by weight. Further, the preparation method of the candesartan cilexetil capsule comprises the following steps: (a) Preparing and treating raw and auxiliary materials, namely weighing candesartan cilexetil, lactose, corn starch, polyethylene glycol 8000, hydroxypropyl cellulose, carboxymethylcellulose calcium and magnesium stearate with prescription amount for later use; (b) Preparing adhesive, namely weighing the prescription dose of hydroxypropyl cellulose, adding the hydroxypropyl cellulose into purified water, and preparing a clear and transparent solution with the concentration of 5 percent for standby; (c) Granulating in one step by using a fluidized bed, namely putting the candesartan cilexetil, lactose, corn starch and polyethylene glycol 8000 weighed in the step (a) into a fluidized drying granulator, starting a fan with the frequency of 5-50 Hz, setting the air inlet temperature to 40-60 ℃, controlling the material temperature to be less than or equal to 50 ℃, starting spraying liquid, spraying the prepared adhesive, and granulating in one step at the liquid supply speed of 50-150 rpm to finally obtain granules with the moisture of less than or equal to 3.5 percent for later use; (d) Finishing, namely putting the dry particles obtained in the step (c) into a pulverizer, and finishing the particles by using a screen with the screen aperture of 0.1mm to obtain finished particles with certain particle size distribution for later use; (e) Adding the particles obtained in the step (d) and the weighed carboxymethylcellulose calcium into a butt-clamp square cone mixer, setting the mixing rotating speed to be 10rpm, mixing for 10min, adding the weighed magnesium stearate, and continuing mixing for 5min to obtain total mixed particles for later use; (f) And (3) filling the capsule, namely filling the total mixed particles obtained in the step (e) into a gelatin hollow capsule by usin