CN-115192553-B - Isosorbide mononitrate oral membrane preparation and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an isosorbide mononitrate oral solution film and a preparation method thereof. The isosorbide mononitrate oral solution film preparation comprises a medicine-containing layer and isolation layers compounded on the upper surface and the lower surface of the medicine-containing layer, wherein the medicine-containing layer comprises, by mass, 10-60% of cyclodextrin inclusion isosorbide mononitrate, 20-80% of film forming materials, 0-20% of plasticizers and 0-10% of auxiliary materials, and the isolation layers comprise, by mass, 70-100% of film forming materials, 0-30% of plasticizers and 0-10% of auxiliary materials. The isosorbide mononitrate oral solution film prepared by the invention has the advantages of smooth appearance, good taste and uniform drug content, and is quickly dissolved under the action of saliva after being taken in, so that the absorption is released, the drug delivery compliance is greatly improved, and the problem of surface crystallization after the isosorbide mononitrate is placed for a long time is solved.

Inventors

• ZHENG JIAQING
• DONG XU
• GAO SHENJUN
• ZHANG TAO
• YANG HUAIZHI
• HAO LEILEI

Assignees

• 山东齐都药业有限公司

Dates

Publication Date

20260508

Application Date

20220729

Claims (4)

1. 1. The isosorbide mononitrate oral membrane preparation is characterized by comprising a medicine-containing layer and isolating layers compounded on the upper surface and the lower surface of the medicine-containing layer, wherein the medicine-containing layer comprises the following raw materials in percentage by mass: 10 to 60 percent of cyclodextrin inclusion isosorbide mononitrate, 20-80% Of film forming material, 5-20% Of plasticizer, 0.5-10% Of auxiliary materials; The isolation layer comprises the following raw materials in percentage by mass: 70-90% of film forming material, 9-25% Of plasticizer, 1-5% Of auxiliary materials; In the isosorbide mononitrate included by the cyclodextrin, the mass ratio of the cyclodextrin to the isosorbide mononitrate is 0.5:1-3:1; the cyclodextrin is hydroxypropyl betacyclodextrin or hydroxypropyl gamma cyclodextrin; the film forming material is one or more of hypromellose, hydroxypropyl cellulose, pullulan, polyvinyl alcohol or polyvinylpyrrolidone; the plasticizer is one or more of glycerol, polyethylene glycol or propylene glycol; The auxiliary materials comprise one or two of flavoring agents or coloring agents; the preparation method of the isosorbide mononitrate oral soluble film comprises the following steps: (1) Adding cyclodextrin into water, stirring and dissolving, adding isosorbide mononitrate, stirring and clathrating at 45-55 ℃ for 0.5-2 hours, cooling to room temperature, then adding plasticizer, auxiliary materials and film forming materials, uniformly mixing, and defoaming to obtain the medicine-containing layer glue solution; (2) Adding the plasticizer and the auxiliary materials into water, stirring and dissolving, then adding the film forming material, uniformly mixing, and defoaming to obtain the isolation layer glue solution; (3) Coating an isolation layer glue solution, a medicine-containing layer glue solution and an isolation layer glue solution on the release film in sequence, drying, and then stripping from the release film to obtain the isosorbide mononitrate oral solution film.
2. 2. The isosorbide mononitrate orosol preparation of claim 1 wherein the thickness of the drug-containing layer is 10-100 μm and the thickness of the isolation layer is 10-100 μm.
3. 3. The isosorbide mononitrate oromembrane formulation of claim 1 wherein the flavoring agent is one or more of sucralose, aspartame, sodium saccharin.
4. 4. The isosorbide mononitrate oral film preparation of claim 1, wherein vacuum defoaming or static defoaming is adopted in the defoaming treatment.

Description

Isosorbide mononitrate oral membrane preparation and preparation method thereof Technical Field The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an isosorbide mononitrate oral solution film and a preparation method thereof. Background Isosorbide mononitrate, which has the chemical name of 1,4:3, 6-dianhydro-D-sorbitol-5-mononitrate, has the molecular formula of C 6H9NO6 and the molecular weight of 191.14, and has the structural formula as follows: isosorbide mononitrate is a nitrate anti-angina drug, isosorbide mononitrate is a main bioactive metabolite of isosorbide dinitrate, and the main pharmacological action is to relax vascular smooth muscle as other organic nitrate. Isosorbide mononitrate releases Nitric Oxide (NO), which is the same as endothelial relaxing factor, activates guanylate cyclase, increases cyclic guanylate (cGMP) in smooth muscle cells, relaxes vascular smooth muscle, expands peripheral arteries and veins, and has a stronger effect on vein expansion. Vein dilation reduces blood retention in the periphery, heart rate, left ventricular end diastolic pressure and pulmonary capillary blood embedding pressure (preload), artery dilation reduces peripheral vascular resistance, systolic arterial pressure and mean arterial pressure (afterload), coronary artery dilation increases coronary perfusion rate, and the total effect is that myocardial oxygen consumption is reduced, oxygen supply is increased, and angina pectoris is relieved. The existing isosorbide mononitrate oral dosage forms comprise tablets, sustained release tablets and sustained release capsules, and when the dosage forms are used for administration, water is needed to be used for taking the tablets, the administration is inconvenient, and especially for middle-aged and elderly patients with dysphagia. Moreover, the preparation formulations are produced by adopting the traditional tablet and capsule production processes, and the isosorbide mononitrate is easy to explode due to the fact that the isosorbide mononitrate contains nitro and is heated or impacted, so that the temperature must be strictly controlled, and rough operations such as impact, beating and the like must be avoided in the traditional tablet and capsule production process, so that safety accidents are avoided, and higher requirements are put on safety production. An oral film is an oral preparation prepared by uniformly dispersing the active ingredients of the medicine in a film forming material, and has the size, shape and thickness similar to those of a stamp. Can dissolve and release the active ingredients in the oral cavity in a short time, and can be absorbed by the oral mucosa or absorbed by the gastrointestinal tract after swallowing, so that the preparation has quick response and high bioavailability. The medicine can be rapidly and accurately administered at any time and any place without water, and the medicine taking time is not delayed. The beneficial group of isosorbide mononitrate preparations is mainly middle-aged and elderly patients, and the patients have difficulty in swallowing conventional tablets, so that the dosage form provides a safe and reliable administration way for the elderly and the people with swallowing dysfunction, and improves the compliance of the patients. For example, patent CN103784426B discloses an aripiprazole oral film comprising aripiprazole coated with cyclodextrin, wherein the cyclodextrin is one or more of hydroxypropyl-beta-cyclodextrin or glucosyl-beta-cyclodextrin, and the weight ratio of cyclodextrin to aripiprazole is 1:1-3:1. The membranous preparation is uniform and smooth, is easy to take, can be taken without drinking water, and has the advantages of rapid and complete dissolution, rapid absorption speed, high bioavailability and good curative effect. However, isosorbide mononitrate is slightly soluble in water, has strong fat solubility and penetrability, and can cause crystallization phenomenon to occur along with the increase of the standing time of a preparation product when the oral film agent is directly prepared by adopting the method in the patent CN103784426B, so that the problems of property change, uneven product content and the like are solved. It is also mentioned in patents CN103610650B and CN110420192B that crystallization phenomenon is a common phenomenon for isosorbide mononitrate formulations. Disclosure of Invention The invention aims to solve the technical problems of providing the isosorbide mononitrate oral solution film which has the advantages of smooth appearance, good taste and uniform drug content, is quickly dissolved under the action of saliva after entering, further releases and absorbs, greatly improves the drug delivery compliance, and simultaneously solves the problem of surface crystallization after the isosorbide mononitrate is placed for a long time. The isosorbide mononitrate oral solution film consists of a medicine-con