Captopril micro-tablet and preparation method thereof
By developing captopril micro-tablet preparations, the problem that existing captopril drug dosage forms cannot meet the needs of small doses and individualized medications has been solved, and precise medication administration to the elderly and young children has been achieved and the compliance of medication is improved.
Patent Information
- Application Number
- CN202411099969.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2016-06-20
- Publication Date
- 2024-12-13
AI Technical Summary
The existing captopril drug dosage forms are mainly tablets and pills for adults, which cannot meet the needs of small doses or individualized medication, especially for children and the elderly. The volume of conventional dosage forms is too large, resulting in poor drug compliance.
Develop captopril micro tablet preparations, and prepare small doses, multiple doses of micro tablets through special formulas and processes. Use diluents, adhesives and lubricants to select appropriate shapes and coatings. Technology ensures accurate administration and improves medication compliance, and can be loaded in capsules or used in combination with drug delivery devices.
Accurate administration of drugs to groups with large differences in individual metabolism, such as the elderly and young children, reduces the side effects caused by inaccurate medication, and improves medication compliance. It is especially suitable for occasions where small doses or individualized medication are required.
Smart Images
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Abstract
Description
[0001] This application is a divisional application of the Chinese invention patent application with the application date of June 20, 2016, application number: 201610443201.8, and invention name: "A Captopril Microtablet and Preparation Method Thereof". Technical Field
[0002] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a captopril microtablet, and provides a method for preparing the captopril microtablet. Background Art
[0003] Hypertension refers to a clinical syndrome characterized by increased systemic arterial blood pressure (systolic and / or diastolic blood pressure) (systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg), which may be accompanied by functional or organic damage to organs such as the heart, brain, and kidneys. Hypertension is the most common chronic disease and the most important risk factor for cardiovascular and cerebrovascular diseases. The blood pressure of a normal person fluctuates within a certain range with changes in the internal and external environment. In the overall population, blood pressure levels gradually increase with age, with systolic blood pressure being more obvious, but after the age of 50, diastolic blood pressure shows a downward trend, and pulse pressure also increases accordingly. Blood pressure values and risk factor assessment are the main basis for diagnosing and formulating hypertension treatment plans. The goals of hypertension management are different for different patients. When facing patients, doctors judge the most appropriate blood pressure range for the patient based on the reference standard and their specific circumstances, and adopt targeted treatment measures.
[0004] At present, a series of drugs have been developed for hypertension at home and abroad. Captopril (metoprolol, metoprolol, captopril) is the first generation of effective oral angiotensin-converting enzyme inhibitors (ACEI). Since its introduction in 1997, its efficacy in treating hypertension and congestive heart failure has been recognized. Captopril has a significant antihypertensive effect on various types of hypertension and can improve the heart function of patients with congestive heart failure. It is clinically used for various types of hypertension, especially for severe hypertension that is ineffective with conventional treatments. It can also be used for refractory chronic heart failure.
[0005] Microtablets refer to miniature tablets with a diameter of 1 to 3 mm that are pressed by a special tablet press. Microtablets are dose-dispersible preparations. After oral administration, microtablets are evenly dispersed in the gastrointestinal tract, reducing irritation to the gastrointestinal tract. The gastrointestinal transport and absorption of drugs are less affected by the gastric emptying rate, so the individual differences are small; the drug release behavior of microtablets is the sum of the drug release behaviors of multiple small units that make up a dose. After oral administration, defects in the preparation process of individual small units will not have a serious impact on the drug release behavior of the overall preparation. For people with large individual differences in drug metabolism, such as the elderly and young children, or for drugs whose dosage needs to be adjusted at any time, microtablets are an ideal dosage form. Patients can count and take microtablets according to individualized medication plans, and the measurement is more accurate. Compared with other multi-unit dosage forms, microtablets have more regular shapes and more uniform sizes. Since microtablets are pressed by fixed molds, they have the characteristics of ordinary tablets. Their tablet weight and size are precisely controllable, and the production reproducibility is good. Each microtablet unit has equal size, the same weight, and the same drug content.
[0006] At present, there are only two common dosage forms of captopril preparations used clinically at home and abroad, namely tablets and dripping pills, and all of them are dosage specifications for adults. In situations where small doses must be administered, such as when administering to children, or when the dose needs to be adjusted at any time, such as when administering to the elderly, the existing captopril dosage forms cannot meet the requirements of individualized medication and achieve precise medication. In addition, when taking existing drug dosage forms, due to the large volume of the dosage forms, the compliance of special populations, especially children, is poor. Summary of the invention
[0007] In order to overcome the defects of the prior art, the present invention provides a captopril microtablet preparation. Through a special granulation formula and preparation process, the captopril microtablet of the present invention can be administered multiple times in small doses, especially for people with large individual metabolic differences, such as the elderly and young children, and can be taken accurately. While achieving accurate dosing, various side effects caused by inaccurate medication can be reduced, and for people who have difficulty taking conventional preparations, the compliance of medication can be improved.
[0008] In order to achieve the above-mentioned object of the invention, the present invention provides a captopril microtablet preparation, the prescription raw materials and their dosage ratios are as follows:
[0009] Captopril 0.4-0.8
[0010] Diluent 7.0~8.0
[0011] Adhesive 0.2~0.6
[0012] Lubricant 0.04~0.2.
[0013] The captopril microtablet preparation of the present invention, wherein the raw materials and their dosage ratios in the microtablets are preferably as follows:
[0014] Captopril 0.6
[0015] Thinner 7.6
[0016] Adhesive 0.4
[0017] Lubricant 0.08.
[0018] The diluent is selected from one or more of starch, pregelatinized starch, dextrin, microcrystalline cellulose, and lactose. The binder is selected from one or more of HPMC, povidone, gelatin, poloxamer, microcrystalline cellulose, and polyvinyl pyrrolidone. The lubricant is selected from one or more of magnesium stearate, talc, corn starch, stearic acid, calcium stearate, talc, and calcium behenate.
[0019] The excipients included in the micro-tablet preparation of the present invention are not limited to the types listed in the content of the invention and the examples, and may also include other pharmaceutical excipients, provided that they do not affect the compression molding of the micro-tablets. For example, a surfactant may also be included, and the surfactant may be selected from: sorbitol, mannitol, sodium lauryl sulfate, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether, etc.
[0020] The spatial shape of the microchip can be selected as required in principle. The microchip in the present invention is preferably cylindrical, elliptical or spherical in spatial shape. It is preferably a cylindrical shape with a height and a diameter of 1 to 4 mm. The height and the diameter can be arbitrarily selected as required, such as the height and the diameter can be 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5 mm, 4 mm, etc.
[0021] In the microtablet preparation of the present invention, the surface of the microtablet can also be coated by known methods. For example, the active substance Captopril can be controlled (generally delayed) released in an aqueous medium by applying at least one coating. Suitable controlled release coatings contain water-insoluble waxes or polymers, preferably ethylcellulose.
[0022] The microtablet formulation of the present invention may also contain a coating that can dissolve in a pH-dependent manner, for example, to ensure that the microtablet formulation does not dissolve after passing through the stomach and is not released until it reaches the intestine.
[0023] The present invention can also pack described captopril microtablet preparation into capsule, be prepared as the oral preparation of capsule form, contain a certain number of microtablets of controlled release medicine in the capsule, the number of microtablets is determined according to the single release time and the amount of medicine to be released. The number of microtablets in the capsule is preferably enough for the dosage of once or twice daily administration. The advantage of this dosage form is: the dosage of active ingredient is subdivided between many directly countable microtablets, but because the dosage has been determined in the capsule, the patient does not need to count with trivial details.
[0024] The micro-tablet preparation of the present invention can be used alone or in combination with a special drug delivery device such as a drug dispensing device to provide more convenient and accurate drug delivery.
[0025] Another object of the present invention is to provide a method for preparing captopril microtablets, wherein the microtablets can be prepared by fluidized bed top spray granulation, wet granulation, dry granulation or fluidized bed bottom spray granulation.
[0026] For example, when the top spray granulation process is adopted, the preparation method is as follows: captopril and a binder are added to purified water, and stirred to form a clear and transparent solution as a granulation binder solution for standby use; the diluent is premixed and then placed in the fluidized bed top spray pot; the fluidized bed is opened for blowing, the atomization pressure and the air volume and air inlet temperature are adjusted, and the binder solution is sprayed in at the same time for top spray granulation; after the binder solution is sprayed, the particles are taken out and dry granulated; after the obtained dry particles are evenly mixed with the prescribed amount of lubricant, the mixture is transferred to a high-speed rotary tablet press for tableting to obtain finished tablets.
[0027] Alternatively, when a wet granulation process is adopted, the preparation method is as follows: captopril, a diluent and a binder are placed in the pot of a wet granulator, and after mixing, purified water is sprayed in for wet granulation, wet granulation, and subsequent drying. After drying, the granules are subjected to dry granulation; after the dry granules are uniformly mixed with a prescribed amount of lubricant, the mixture is transferred to a high-speed rotary tablet press for tableting to obtain finished tablets. DETAILED DESCRIPTION
[0028] Embodiment 1:
[0029] name Dosage Captopril 0.6mg Microcrystalline cellulose 102 2.4mg Lactose Flowlac100 5.2mg HPMC E3 0.4mg Stearic acid 0.08mg
[0030] The preparation process is as follows: captopril and HPMC E3 are added to purified water, and stirred to form a clear and transparent solution as a granulation binder solution for standby use; microcrystalline cellulose 102 and lactose Flowlac 100 are premixed and placed in a fluidized bed top spray pot; the fluidized bed is opened for blowing, the atomization pressure and the air volume and air inlet temperature are adjusted, and the binder solution is sprayed at the same time for top spray granulation; after the binder solution is sprayed, the particles are taken out and dry granulated; the obtained dry particles are evenly mixed with a prescribed amount of stearic acid, and the mixed material is transferred to a high-speed rotary tablet press for tableting to obtain finished captopril micro-tablets.
[0031] Embodiment 2:
[0032]
[0033]
[0034] The preparation process is as follows: captopril, lactose Flowlac100 and HPMC E3 are placed in the pot of a wet granulator, the paddles are turned on for initial mixing for 10 minutes, and after mixing, the paddles are turned on and purified water is sprayed in for wet granulation; after the purified water is sprayed, granulation is continued for 5 minutes; then the obtained wet granules are wet granulated, and then placed in a fluidized bed for drying, and the granules after drying are dry granulated; after the dry granules are uniformly mixed with the prescribed amount of stearic acid, the mixture is transferred to a high-speed rotary tablet press for tableting to obtain finished captopril micro-tablets.
[0035] Embodiment 3:
[0036]
[0037] Preparation process: After captopril, microcrystalline cellulose 102 and HPMC E3 are uniformly mixed, the mixture is added to a dry granulator to obtain suitable dry granules; after the granules and stearic acid are uniformly mixed, the mixture is transferred to a high-speed rotary tablet press for tableting to obtain finished tablets.
[0038] Example 4
[0039]
[0040]
[0041] Preparation process: Captopril and povidone K30 are added to purified water and stirred to form a clear and transparent solution as a granulation binder solution for standby use; microcrystalline cellulose 102 and pregelatinized starch are premixed and placed in a fluidized bed top spray pot; the fluidized bed is opened for air blowing, the atomization pressure and the air volume and inlet temperature are adjusted, and the binder solution is sprayed in for top spray granulation; after the binder solution is sprayed, the particles are taken out and dry granulated; the obtained dry particles are evenly mixed with the prescribed amount of stearic acid, and the mixture is transferred to a high-speed rotary tablet press for tableting to obtain a finished microtablet preparation.
Claims
1. A captopril microtablet, characterized in that The raw materials and their dosage in the micro-sheets are as follows:
2. The microchip according to claim 1, characterized in that The raw materials and their dosage in the micro-sheets are as follows:
3. The microtablet according to claim 1 or 2, wherein the diluent is selected from one or more of starch, pregelatinized starch, dextrin, microcrystalline cellulose, and lactose.
4. The microtablet according to any one of claims 1 to 3, wherein the binder is selected from one or more of HPMC, povidone, gelatin, poloxamer, microcrystalline cellulose, polyvinyl pyrrolidone, preferably HPMC E5.
5. The microtablet according to any one of claims 1 to 4, wherein the lubricant is selected from one or more of magnesium stearate, talc, corn starch, stearic acid, calcium stearate, talc, and calcium behenate, and the lubricant is preferably stearic acid. 6 . The microplate according to claim 1 , wherein the microplate has a cylindrical, elliptical or spherical spatial shape.
7. The microplate according to any one of claims 1 to 6, wherein the microplate is in a cylindrical shape with a height of 1 to 3 mm and a diameter of 1 to 3 mm.
8. The microtablet according to any one of claims 1 to 7, wherein the microtablet can be coated with one or more layers of coating.
9. The method for preparing the captopril microtablet according to any one of claims 1 to 8, characterized in that The micro-tablets are prepared by fluidized bed top spray granulation, wet granulation, dry granulation, direct powder tableting or fluidized bed bottom spray granulation.