CN107519137A - A kind of captopril microplate and preparation method thereof - Google Patents

Abstract

The invention discloses a kind of captopril microplate preparation for treating hypertension class disease, a kind of and method for preparing captopril microplate, pass through the preparation methods such as top spray fluidized bed granulation, the good captopril microplate of compressibility has been prepared, the captopril microplate of the present invention can be with low dose of multiple dosing, especially for the big crowd of individual Difference of Metabolism, such as the elderly and child, it can count and take, accomplish precisely to be administered, and the crowd being had any problem for taking conventional formulation, the compliance of medication can be improved.

Description

A kind of captopril microchip and preparation method thereof

technical field

The invention belongs to the technical field of pharmaceutical preparations, in particular to a captopril microtablet and a method for preparing the captopril microtablet.

Background technique

Hypertension (hypertension) refers to an increase in systemic arterial blood pressure (systolic and/or diastolic) as the main feature (systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≥ 90 mm Hg), which may be accompanied by heart, brain, kidney, etc. Clinical syndrome of functional or organic damage to organs. Hypertension is the most common chronic disease and the main 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 whole population, the blood pressure level gradually increases with age, especially the systolic blood pressure, but the diastolic blood pressure shows a downward trend after the age of 50, and the pulse pressure also increases accordingly. Blood pressure value and risk factor assessment are the main basis for the diagnosis and formulation of hypertension treatment plan. Different patients have different goals of hypertension management. Doctors judge the most appropriate blood pressure for the patient based on the reference standard and according to their specific conditions. Scope, the use of targeted treatment measures.

At present, a series of drugs have been developed for hypertension at home and abroad. Captopril (protopril, protopril, and Kaibotong) is the first generation of oral and effective angiotensin converting enzyme inhibitors. (ACEI), since it came out in 1997, its antihypertensive and therapeutic effects on congestive heart failure have been recognized. Captopril has obvious antihypertensive effect on various types of hypertension, and can improve cardiac function in patients with congestive heart failure. It is clinically used for various types of hypertension, especially for severe hypertension that is ineffective by conventional therapy. It can also be used for refractory chronic heart failure.

Microtablets refer to microtablets with a diameter of 1 to 3mm pressed by a special tablet press. Microtablets are dose-dispersible preparations. After oral administration of microtablets, patients are evenly dispersed in the gastrointestinal tract, reducing the risk of adverse reactions. The irritation of the gastrointestinal tract, the gastrointestinal transit 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, oral administration The 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. Counting and taking, the measurement is more accurate. Compared with other multiple unit dosage forms, microtablets are more regular in shape and more uniform in size. Because the microtablet is compressed by a fixed mold, it has the characteristics of an ordinary tablet. Its weight and size are precisely controllable, and the production reproducibility is good. Each microtablet unit has the same size and the same weight. The content is the same.

At present, there are only two common dosage forms of captopril preparations used clinically at home and abroad, tablet and drop pill, and all of them are dosage specifications for adults. In occasions that need to be adjusted at any time, such as when administering drugs to the elderly, the existing dosage forms of captopril cannot meet the requirements of individualized drug administration and achieve precise drug administration. In addition, when taking the existing pharmaceutical dosage form, due to the excessive volume of the dosage form, for special groups of people, especially children, the compliance of taking the medicine is poor.

Contents of the invention

In order to overcome the defects of the prior art, the invention provides a captopril microtablet preparation. Through the special granulation formula and preparation process, the captopril microtablets of the present invention can be administered multiple times in small doses, especially for people with large differences in individual metabolism, such as the elderly and young children, they can be taken accurately, At the same time of precise drug administration, various side effects caused by inaccurate drug use can be reduced, and for people who have difficulty taking conventional preparations, the compliance of drug taking can be improved.

For realizing the foregoing invention object, the present invention provides a kind of captopril microtablet preparation, and its prescription raw material and consumption ratio thereof are as follows:

Captopril microtablet preparation of the present invention, wherein in said microtablet, raw material and consumption ratio thereof are preferably as follows:

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 polyvinylpyrrolidone. The lubricant is selected from one or more of magnesium stearate, talcum powder, corn starch, stearic acid, calcium stearate, talc, and calcium behenate.

The excipients included in the microtablet preparation of the present invention are not limited to the types listed in the summary of the invention and the examples, and may also contain other pharmaceutical excipients, provided that the compression molding of the microtablets is not affected. 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, and the like.

The spatial shape of the microplate can in principle be selected according to requirements. The microchips in the present invention preferably have a cylindrical, elliptical or spherical spatial shape. It is preferably a cylinder with a height and a diameter of 1 to 4 mm, and the height and diameter can be arbitrarily selected according to needs, such as the height and diameter can be 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5 mm, 4 mm, etc., respectively.

In the microtablet preparation of the present invention, the surface of the microtablets may also be coated by a known method. The controlled (generally delayed) release of the active substance captopril in an aqueous medium can be achieved, for example, by applying at least one coating. Suitable controlled release coatings contain water insoluble waxes or polymers, preferably ethylcellulose.

The microtablet preparations according to the invention may also contain coatings which dissolve, for example, in a pH-dependent manner, ensuring that the microtablet preparations pass through the stomach without dissolving until they reach the intestinal tract.

In the present invention, the captopril microtablet preparation can also be packed into a capsule to be prepared as an oral preparation in the form of a capsule. The capsule contains a certain number of microtablets that can control the drug release. time and the amount of drug that will be released. The number of minitablets in the capsule is preferably sufficient for one or two daily doses. The advantage of using this dosage form is that the dose of the active ingredient is subdivided between many directly countable microtablets, but since the dose is already determined in the capsule, the patient does not have to tediously count.

The microtablet preparation of the present invention can be used alone, and can also be used in conjunction with a special drug delivery device such as a drug distribution device to provide more convenient and accurate drug delivery.

Another object of the present invention is to provide a preparation method of captopril microtablets, which can adopt fluidized bed top spray granulation, wet granulation, dry granulation or fluidized bed bottom spray granulation method Prepared.

For example, when the top-spray granulation process is adopted, the preparation method is as follows: add captopril and the binder into purified water, stir until a clear and transparent solution is formed as the granulation binder solution for later use; premix the diluent , put it into the fluidized bed top spray pot; turn on the fluidized bed blast, adjust the atomization pressure and air volume inlet temperature, and spray the binder solution into the top spray granulation at the same time; after the binder solution is sprayed in, , take out the granules, and perform dry sizing; after uniformly mixing the obtained dry granules with the prescribed amount of lubricant, transfer the mixed material to a high-speed rotary tablet press for tableting, and then obtain finished tablets.

Or when using the wet granulation process, the preparation method is: put captopril, diluent and binder in the pot of the wet granulator, after mixing, spray purified water for wet granulation, wet granulation, Then dry, and after drying, the granules are dry-sized; after the dry granules are evenly mixed with the prescribed amount of lubricant, the mixed material is transferred to a high-speed rotary tablet press for tablet compression, and the finished tablet is obtained.

detailed description

Example 1:

name Dosage Captopril 0.6mg Microcrystalline Cellulose 102 2.4mg Lactose Flowlac100 5.2mg HPMC E3 0.4mg stearic acid 0.08mg

The preparation process is as follows: add captopril and HPMC E3 into purified water, stir until a clear and transparent solution is formed as a granulation binder solution for later use; premix microcrystalline cellulose 102 and lactose Flowlac100, and put them into the fluidized Inside the spray pot on the top of the bed; turn on the fluidized bed blast, adjust the atomization pressure and air volume inlet temperature, and spray the binder solution into the top spray granulation at the same time; after the binder solution is sprayed in, take out the granules, Carry out dry sizing; after the obtained dry granules are uniformly mixed with the stearic acid of the prescribed amount, the mixed material is transferred to a high-speed rotary tablet press for tableting, and the finished captopril microtablets are obtained.

Example 2:

The preparation process is as follows: put captopril, lactose Flowlac100 and HPMC E3 in the pot of the wet granulator, turn on the paddle for 10 minutes of initial mixing, after the mixing is completed, turn on the paddle and spray purified water for wet granulation; Continue to granulate for 5 minutes after the water is sprayed in; then the obtained wet granules are subjected to wet granulation, and then put into a fluidized bed for drying. Finally, the mixed material is transferred to a high-speed rotary tablet press for tableting to obtain finished captopril microtablets.

Example 3:

Preparation process: After mixing captopril, microcrystalline cellulose 102 and HPMC E3 evenly, add the mixed material into a dry granulator to obtain suitable dry granules; after uniformly mixing the granules and stearic acid, mix the mixed material Transfer to a high-speed rotary tablet press for tablet compression to obtain finished tablets.

Example 4

name Dosage Captopril 0.7mg Microcrystalline Cellulose 102 3.0mg pregelatinized starch 4.8mg Povidone K30 0.4mg stearic acid 0.05mg

Preparation process: add captopril and povidone K30 into purified water, stir until a clear and transparent solution is formed as a granulation binder solution for later use; premix microcrystalline cellulose 102 and pregelatinized starch, and put into the fluidized bed top spray pot; turn on the fluidized bed blast, adjust the atomization pressure and air volume inlet temperature, and spray the binder solution into the top spray granulation at the same time; after the binder solution is sprayed in, put The granules are taken out and dry-sized; after the obtained dry granules are evenly mixed with the prescribed amount of stearic acid, the mixed material is transferred to a high-speed rotary tablet press for tableting, and the finished microtablet preparation is obtained.

Claims (9)

1. a kind of captopril microplate, it is characterised in that in the microplate under raw material and its amount ratio：

2. microplate according to claim 1, it is characterised in that in the microplate under raw material and its amount ratio：

3. microplate according to claim 1 or 2, wherein described diluent is selected from starch, pregelatinized starch, dextrin, micro- One or more in crystalline cellulose, lactose.

4. according to the microplate described in any one of claims 1 to 3, wherein described adhesive is selected from：HPMC, PVP, gelatin, One or more in poloxamer, microcrystalline cellulose, polyvinylpyrrolidone, preferably HPMC E5.

5. according to the microplate described in any one of Claims 1 to 4, wherein the lubricant is selected from：Magnesium stearate, talcum powder, jade One or more in rice starch, stearic acid, calcium stearate, talcum, behenic acid calcium, lubricant are preferably stearic acid.

6. according to the microplate described in any one of Claims 1 to 5, wherein the microplate is in cylindrical, oval or spherical sky Between shape.

7. according to the microplate described in any one of claim 1~6, wherein the microplate is in 1~3mm of height, a diameter of 1~3mm Cylinder.

8. according to the microplate described in any one of claim 1~7, wherein the microplate can be coated with one or more layers bag again Clothing.

9. the preparation method of any one of the claim 1~8 captopril microplate, it is characterised in that the microplate is using fluidisation The granulation of bed top spray, wet granulation, dry granulation, direct powder compression or fluid bed bottom spray method of granulating are prepared.