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CN-116650445-B - Isosorbide mononitrate sustained-release capsule and preparation method thereof

CN116650445BCN 116650445 BCN116650445 BCN 116650445BCN-116650445-B

Abstract

The invention provides an isosorbide mononitrate slow-release capsule and a preparation method thereof, and the isosorbide mononitrate slow-release capsule is characterized in that a medicine carrying layer, a slow-release layer, a quick-release layer and a protective layer of the isosorbide mononitrate slow-release capsule are respectively coated by a fluidized bed granulating and coating machine. The isosorbide mononitrate sustained-release capsule has the advantages of good stability, small side effect, simple preparation process, simple and easy operation of equipment, low labor intensity, economy and safety. Meanwhile, the prescription and the preparation method are more economical and are suitable for industrial production.

Inventors

  • SHEN ZHAOJUN
  • GUO HONGTAO

Assignees

  • 山东新时代药业有限公司

Dates

Publication Date
20260508
Application Date
20220217

Claims (4)

  1. 1. The preparation method of the isosorbide mononitrate slow-release capsule is characterized in that the slow-release capsule consists of a medicine carrying layer, a slow-release layer, a quick-release layer and a protective layer, wherein the medicine carrying layer comprises a blank sucrose pellet core, isosorbide mononitrate, lactose and purified water, the slow-release layer comprises ethyl cellulose, purified water and absolute ethyl alcohol, the quick-release layer comprises isosorbide mononitrate, hypromellose and purified water, and the protective layer comprises a polyvinyl alcohol polyethylene glycol copolymer, talcum powder and purified water; the slow-release capsule comprises the following components in parts by weight: the medicine carrying layer comprises 20-25 parts of blank sucrose pellet cores, 30-40 parts of isosorbide mononitrate, 3-6 parts of lactose and 250.7-399.5 parts of purified water; The slow release layer comprises 5-8 parts of ethyl cellulose, 5.35-25.67 parts of purified water and 48.15-231.03 parts of absolute ethyl alcohol; the quick release layer comprises 10-20 parts of isosorbide mononitrate, 2.5-7.5 parts of hypromellose and 102.5-170 parts of purified water; the protective layer comprises 1-5 parts of polyvinyl alcohol polyethylene glycol copolymer, 0.5-1 part of talcum powder and 20-50 parts of purified water; the preparation steps are as follows: (1) The preparation of the drug-carrying layer comprises the steps of respectively adding isosorbide mononitrate and lactose into purified water, stirring until the isosorbide mononitrate and lactose are completely dissolved, preparing into isosorbide mononitrate and lactose coating solution, preheating a blank sucrose pill core in a fluidized bed granulating and coating machine, spraying the prepared isosorbide mononitrate and lactose coating solution on the preheated blank sucrose pill core to prepare drug-carrying layer pellets, and carrying the theoretical weight gain of the drug-carrying layer to be 152-205%; (2) Slowly adding ethyl cellulose into a 90% ethanol solution, stirring and dissolving, adding talcum powder, stirring and dispersing fully to prepare a 90% ethanol coating solution of ethyl cellulose and talcum powder, and coating the dried pellets obtained in the step (1) with a slow release layer, wherein the theoretical weight of the slow release layer pellets is increased by 10.6% -20.7%; (3) Slowly dispersing the hypromellose in purified water, stirring until the hypromellose is completely dissolved, adding isosorbide mononitrate, stirring and dissolving to prepare isosorbide mononitrate and hypromellose coating solution, and coating the dried pellets obtained in the step (2) with a quick-release layer, wherein the theoretical weight gain of the quick-release layer pellets is 22.4% -34.6%; (4) The preparation of the protective layer comprises slowly adding the polyvinyl alcohol polyethylene glycol copolymer into purified water, stirring until the polyvinyl alcohol polyethylene glycol copolymer is completely dissolved, adding talcum powder, stirring and dispersing fully to prepare a polyvinyl alcohol polyethylene glycol copolymer and talcum powder coating solution, coating the dried pellets obtained in the step (3) with the protective layer, wherein the theoretical weight of the protective layer is increased by 3.5% -8.5%; (5) Filling capsules according to the content; wherein the medicine carrying layer, the slow release layer, the quick release layer and the protective layer are coated by a fluidized bed granulating and coating machine; Wherein, the material temperature is controlled to be 39 ℃ plus or minus 5 ℃ when the medicine carrying layer in the step (1) is coated, the atomization pressure is 0.2-0.4MPa, the spray speed is 3-12rpm, the drying material temperature is 56 ℃, the material temperature is controlled to be 29 ℃ plus or minus 4 ℃ when the medicine carrying layer in the step (2) is coated, the atomization pressure is 0.1-0.4MPa, the spray speed is 5-15rpm, and the drying material temperature is 45 ℃.
  2. 2. The preparation method of claim 1, wherein the slow release capsule comprises the following components in parts by weight: the medicine carrying layer comprises 20 parts of blank sucrose pill core, 35 parts of isosorbide mononitrate, 3 parts of lactose and 250.7 parts of purified water; the slow release layer comprises 5 parts of ethyl cellulose, 9 parts of purified water and 83 parts of absolute ethyl alcohol; The quick-release layer comprises 15 parts of isosorbide mononitrate, 2.5 parts of hypromellose and 105 parts of purified water; The protective layer comprises 3 parts of polyvinyl alcohol polyethylene glycol copolymer, 0.5 part of talcum powder and 33 parts of purified water.
  3. 3. The method of claim 1, wherein the isosorbide mononitrate slow release capsules have an isosorbide mononitrate release rate of at least 25%, 38% -58%, 55% -75% and 80% of the indicated amount at 0.5, 2, 4 and 8 hours, respectively.
  4. 4. The preparation method according to claim 1, wherein the material temperature is controlled to be 39+/-5 ℃ during the quick-release coating in the step (3), the atomization pressure is 0.2-0.4MPa, the spraying speed is 5-30rpm, the material temperature is controlled to be 56 ℃ during the drying, and the material temperature is controlled to be 41+/-4 ℃ and the material temperature is controlled to be 56 ℃ during the coating of the protective layer in the step (4).

Description

Isosorbide mononitrate sustained-release capsule and preparation method thereof Technical Field The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to an isosorbide mononitrate sustained-release capsule and a preparation method thereof. Background Isosorbide mononitrate can be classified into 5-isosorbide mononitrate and 2-isosorbide mononitrate. Isosorbide mononitrate, also called 5-isosorbide mononitrate (Isosorbide-mononitrate), is a long-acting nitrate anti-angina drug, has the same action mechanism as nitroglycerin, but longer action time, is a main active metabolite in the body of isosorbide mononitrate, and has the advantages of quick oral absorption, high absolute bioavailability and small individual difference. The main pharmacological action is to relax vascular smooth muscle, reduce peripheral vascular resistance and left ventricular contraction resistance, reduce oxygen consumption of heart and improve blood supply in ischemic area. The isosorbide mononitrate has a biological half-life of 4-5 h, can be used for preventing and treating angina pectoris, can be used for long-term treatment of coronary heart disease, preventing vasospasm and mixed type heart-lay disease, is also suitable for long-term treatment after myocardial infarction and chronic heart failure, is used in combination with digitalis and/or diuretics, and is one of the best medicines for preventing and treating angina pectoris at present. Isosorbide mononitrate was first used clinically in federal germany in 1975. The chemical name of the catalyst is 3, 6-dianhydro-D-sorbitol-5-nitrate, which is white needle crystal or crystalline powder, odorless, soluble in methanol or acetone, soluble in chloroform or water, almost insoluble in hexane, and easy to explode under heating or impact. At present, the clinical application dosage forms of isosorbide mononitrate comprise common dosage forms such as tablets, injections and the like, and the frequent administration times and the large fluctuation of blood concentration are caused, and the frequent administration is easy to generate drug resistance, is easy to cause more side reactions and even poisoning, or is difficult to play a role. The slow release preparation quick release layer medicine can quickly take effect to reach the blood concentration, the slow release layer medicine is slowly released to maintain the blood concentration, and the peak valley fluctuation of the blood concentration is reduced or avoided, so that the medicine can continuously exert the curative effect more smoothly, the safety of clinical medicine application is improved, and the adverse reaction of the medicine is reduced. The isosorbide mononitrate sustained release preparation is administrated once daily during the period of taking medicine, reduces the times of taking medicine, basically has no occurrence of drug resistance, greatly reduces the occurrence probability of angina pectoris of patients at night and improves the compliance of the patients. Isosorbide mononitrate sustained release capsules were originally developed by Xu Waci pharmaceutical company in germany. Isosorbide mononitrate sustained release capsules produced by the pharmaceutical company of Germany Xu Waci in 1992 are marketed in China under the trade nameIn 2007, global union of the German Xu Waci pharmaceutical group was completed by the pharmaceutical company (UCB). In 2008, the combination in China was preferably completed compared to pharmaceutical company (UCB) and Zhuhai Xu Waci pharmaceutical Co. In 2012, the Zhuhai Xu Waci pharmaceutical Co., ltd, which is the sole company of the better than pharmaceutical Co., ltd (UCB), has now been examined and confirmed by the national food and drug administration to determine that isosorbide mononitrate sustained-release capsules produced by the better than (Zhuhai) pharmaceutical Co., ltd(50 Mg) as a raw ground product. Patent 201610630326.1 discloses a method for preparing isosorbide mononitrate capsules. Before preparing the pellets, the raw materials and the filler are mixed and crushed by an air flow crusher, after crushing, the quick-release pellets of isosorbide mononitrate are prepared by a multifunctional pill coating machine, the slow-release pellets of isosorbide mononitrate are prepared by the multifunctional pill coating machine, and then the quick-release pellets and the slow-release pellets are mixed and filled into capsules. However, the method is also high in energy consumption and difficult to produce in large scale. Patent 201811311153.2 discloses a method for preparing isosorbide mononitrate capsules. Preparing a soft material by a wet granulator, preparing a quick-release component by using extrusion-spheronization equipment, and drying. The quick-release component is divided into two parts according to the proportion of 70% and 30% after drying, 70% of the quick-release component is used for further slow-release coati