CN111184699A

CN111184699A - Nifedipine controlled release capsule and preparation method thereof

Info

Publication number: CN111184699A
Application number: CN202010271461.8A
Authority: CN
Inventors: 胡连栋
Original assignee: Heibei University
Current assignee: Heibei University; Hebei University
Priority date: 2020-04-09
Filing date: 2020-04-09
Publication date: 2020-05-22

Abstract

The invention provides a nifedipine controlled release capsule and a preparation method thereof, wherein the controlled release capsule is prepared by filling nifedipine, polyoxyethylene and organic acid into a capsule shell and coating the capsule shell; wherein the mass ratio of the nifedipine to the polyoxyethylene to the organic acid is as follows: nifedipine, polyoxyethylene and organic acid = 10-90: 1-15: 1-30, and the coating is prepared by mixing cellulose, a plasticizer and a pore-foaming agent, and the weight ratio of the components is as follows: cellulose, plasticizer and pore-forming agent = 10-50: 0-15: 1-25. The invention does not need double-layer tabletting, laser or mechanical perforation, has simple preparation process, low cost and stable drug release rate, basically realizes zero-order release within 24 hours and has complete drug release; the preparation can be administered once a day, and the patient compliance is improved.

Description

Nifedipine controlled release capsule and preparation method thereof

Technical Field

The invention relates to the technical field of pharmaceutical preparations, in particular to a nifedipine controlled-release capsule and a preparation method thereof.

Background

Hypertension is one of the most common cardiovascular diseases in the world today and is also a major risk factor for cardiovascular and cerebrovascular diseases. The number of the existing hypertension patients in China exceeds 1 hundred million, and the hypertension patients grow at the speed of more than 300 million every year. Nifedipine has better curative effect as a first-line antihypertensive drug.

Nifedipine (Nifedipine) chemical name: 1, 4-dihydro-2, 6-dimethyl-4- (2-nitrophenyl) -3, 5-pyridinedicarboxylic acid dimethyl ester is clinically used for preventing and treating coronary heart disease and angina pectoris, and is suitable for various types of hypertension. The ordinary nifedipine preparation needs to be taken three times a day, and cannot well control the stability of blood concentration in a body and maintain the stability of blood pressure; the fluctuation of blood concentration can bring adverse reactions such as headache, flushing, fast increase of heart rate, dizziness, hypodynamia, nausea, vomiting and the like, Bayer companies adopt osmotic pump controlled release technology to develop nifedipine controlled release tablets successfully, and the osmotic pump controlled release system adopting unique laser drilling controls a release system, so that the nifedipine controlled release tablets are taken once a day, are released at a constant speed within 24 hours, have stable blood concentration, remarkable blood pressure reduction effect, reduce adverse reactions and maintain the blood pressure in a more stable state every day.

Osmotic pump controlled release tablets are the most ideal oral controlled release preparation so far, and take osmotic pressure as a driving force to enable the medicine to reach zero-order release. Its advantages are: the administration time is prolonged, the administration times are reduced, and the times and the degree of adverse reactions are reduced; the medicine release is slightly influenced by in vivo conditions such as pH, gastrointestinal peristalsis, food and the like, has better in vivo and in vitro correlation, and greatly improves the safety and the effectiveness of the medicine.

Currently available osmotic pump tablets are classified into single-chamber osmotic pump tablets and double-chamber osmotic pump tablets according to the structural characteristics of the tablets. Generally, water-soluble drugs can be made into single-layer osmotic pump controlled release tablets, while poorly soluble drugs can be made into double-layer osmotic pump controlled release tablets. The single-layer osmotic pump tablet consists of a tablet core and a semipermeable membrane, wherein the tablet core is prepared by adding an osmotic accelerator or other auxiliary materials into a medicament, and the tablet core is prepared by drilling by using laser or mechanical technology after coating. One layer of the double-layer osmotic pump tablet contains medicines and auxiliary materials, and the other layer contains water-swellable penetration-promoting polymer. The preparation process is complex, and the requirements on auxiliary materials of the tablet core, the coating and production equipment are higher.

Nifedipine controlled release tablets (trade name: bisimir) produced by Bayer company are double-layer osmotic pump preparations, the preparation process is complex, firstly, double-layer tablets are pressed, then semipermeable membranes are wrapped, and then mechanical or laser drilling is carried out. In the prescription of the nifedipine controlled-release tablet, a medicine-containing layer is prepared from the medicine and other auxiliary materials, a boosting layer is prepared from polyoxyethylene, and after the boosting layer absorbs water and expands, suspension in the medicine-containing layer is pushed to be released from a medicine release hole.

If a double-layer tablet structure is not adopted, the polyoxyethylene serving as the boosting agent is directly mixed with the medicine, the boosting agent and the medicine expand and are discharged from a pore channel after water absorption expansion, and high osmotic pressure is difficult to form in the microenvironment of the tablet core to maintain the effective medicine release speed, so that the constant-speed release of the medicine cannot be ensured.

At present, the literature reports the use of cellulose acetate to prepare microporous capsule shells. The report of preparing the microporous osmotic pump capsule is that the medicine is filled after being filled in the capsule shell, and the capsule body and the capsule cap are sealed by adopting the sealing liquid. However, the sealing process is to manually seal each capsule under laboratory conditions, and large-scale industrial production cannot be realized.

The Chinese invention patent CN105920000A (publication number) discloses a nifedipine sustained-release preparation invented by the Guangdong globulus of the Chinese medicine group and a preparation method thereof. Wherein nifedipine and pharmaceutically acceptable auxiliary materials are prepared into a drug-containing sustained-release pellet core and a drug-containing quick-release layer. From the medicine dissolution curve, the accumulative release amount of a test sample in different condition media for 5-6 hours reaches more than 80%. The slow release time can only reach more than 6 hours.

The Chinese invention patent CN102429874A (publication number) discloses nifedipine skeleton type sustained-release pellets invented by Shenyang pharmaceutical university, and a preparation method and application thereof. Wherein, nifedipine liquid co-ground material and related auxiliary materials are used for preparing the osteogenic frame sustained-release pellet. From the dissolution curve of the drug, the release of the test sample reaches 40% in about 2 hours, 50% in about 8 hours, and the release power of the drug in the later period is insufficient, showing the trend of incomplete release.

In general, although osmotic pump formulations have met with great success in the design of drug delivery systems, they have not been commonly used due to the complexity of the manufacturing process, the problems associated with perforation and coating.

Disclosure of Invention

The invention aims to provide a nifedipine controlled-release capsule and a preparation method thereof, and aims to solve the problem that the preparation process of the existing osmotic pump preparation is complex.

The purpose of the invention is realized by the following technical scheme: a nifedipine controlled release capsule is prepared by filling nifedipine, polyoxyethylene and organic acid into a capsule shell and coating the capsule shell with a coating; wherein the mass ratio of the nifedipine to the polyoxyethylene to the organic acid is as follows: nifedipine, polyoxyethylene and an organic acid are = 1-10: 1-30: 1-10, wherein the organic acid is at least one of tartaric acid, fumaric acid, malic acid and citric acid; the coating is prepared by mixing cellulose, a plasticizer and a pore-foaming agent, and the weight ratio of each component is as follows: cellulose, a plasticizer and a pore-forming agent = 10-50: 0-15: 1-25, and the weight of the coating is increased by 3-20% of that of the uncoated medicine-containing capsule.

The controlled release capsule is prepared by filling nifedipine, polyoxyethylene, organic acid, adhesive and osmotic pressure regulator into a capsule shell and coating the capsule shell; wherein the nifedipine, the polyoxyethylene, the organic acid, the adhesive and the osmotic pressure regulator are in the following mass ratio: nifedipine, polyoxyethylene, an organic acid, an adhesive and an osmotic pressure regulator are = 1-10: 1-30: 1-10: 1-25: 0-30, and the organic acid is at least one of tartaric acid, fumaric acid, malic acid and citric acid; the coating is prepared by mixing cellulose, a plasticizer and a pore-foaming agent, and the weight ratio of each component is as follows: cellulose, a plasticizer and a pore-forming agent = 10-50: 0-15: 1-25, and the weight of the coating is increased by 3-20% of that of the uncoated medicine-containing capsule.

The molecular weight of the polyoxyethylene is 100000-300000. The particle size of the polyoxyethylene is 100-400 μm.

The molecular weight of the polyoxyethylene is 150000-250000. The particle size of the polyoxyethylene is 150-350 μm.

The nifedipine is pretreated into nifedipine micronization, nifedipine preparation solid dispersion or nifedipine preparation cyclodextrin inclusion compound.

The solid dispersion adopts at least one of polyethylene glycol (polyethylene glycol 4000, polyethylene glycol 6000), polyvidone (polyvidone K15, K30 and K90) and polyalcohol (such as fructose and sucrose) as adjuvant.

The cellulose is selected from cellulose acetate or ethyl cellulose; the plasticizer is at least one selected from glycerol, propylene glycol, polyethylene glycol, triethyl citrate, diethyl phthalate, triethyl glycerate and castor oil; the pore-forming agent is selected from at least one of sucrose, lactose, mannitol, polyethylene glycol, hypromellose, hydroxypropyl cellulose, poloxamer and povidone.

The adhesive is selected from at least one of hydroxypropyl methylcellulose, hydroxypropyl cellulose and povidone; the osmotic pressure regulator is at least one selected from sucrose, lactose, glucose, mannitol, sorbitol, fructose, sodium chloride, potassium chloride, sodium sulfate, sodium phosphate, and sodium dihydrogen phosphate.

A preparation method of the nifedipine controlled-release capsule comprises the following steps:

(a) carrying out pretreatment on nifedipine;

(b) uniformly mixing the pretreated nifedipine with an adhesive, an osmotic pressure regulator and an organic acid, and filling the mixture into a capsule shell to prepare a medicine-containing capsule;

(c) dissolving plasticizer, pore-forming agent and cellulose in organic solvent to prepare coating liquid, and coating the drug-containing capsule to obtain the nifedipine controlled-release capsule.

The pretreatment comprises micronization of nifedipine, preparation of solid dispersion of nifedipine or preparation of cyclodextrin inclusion compound of nifedipine; the organic solvent is acetone or a mixture of acetone and isopropanol.

Practice proves that: in the original research of the Bytursin osmotic pump tablet, if a double-layer tabletting technology is not adopted, the technical means of the invention directly takes the polyoxyethylene as the boosting agent to be directly mixed with the medicine, the polyoxyethylene can be expanded and discharged from a pore channel drilled by laser after the tablet core absorbs water and expands, and the osmotic pressure of the tablet core cannot be effectively maintained, so that the later release speed of the preparation is reduced, and the medicine cannot be constantly released.

In the invention, nifedipine and auxiliary materials such as polyoxyethylene, organic acid and the like are uniformly mixed and filled in the capsule. And then coated outside the capsule. Complicated processes such as double-layer tabletting and laser drilling and expensive equipment are not needed. The water enters the medicine layer through the pore-forming agent on the semipermeable membrane, the medicine layer forms suspension under the action of the water and the auxiliary materials such as the penetration enhancer, and the polyoxyethylene expands when meeting water to generate enough osmotic pressure. Due to the blocking effect of the micropores, the polyoxyethylene cannot be released from the capsule shell during the drug release process. Therefore, the polyoxyethylene is always present in the capsule shell, a certain osmotic pressure can be constantly maintained, so that part of drug suspension which can be released at a constant speed can be released through the micropores, when moisture penetrates through the drug layer to contact the expanded pill core, the residual drug suspension is pushed to be released, and the active drug nifedipine can be released at an approximately constant drug release rate.

The nifedipine microporous osmotic pump capsule has the characteristic of controlled release, can release the active medicament nifedipine at an approximately constant rate, is not influenced by factors such as medium environment pH value, gastrointestinal motility, food and the like, has better in vitro and in vivo relativity, can avoid blood concentration fluctuation caused by common oral preparations, reduces the administration times, and greatly improves the safety, effectiveness and compliance of the medicament.

The preparation process is simple, and the adopted equipment is common technical equipment for preparation, so that the preparation process is easy to industrialize. The invention takes polyoxyethylene as the osmotic pump booster to be evenly mixed with auxiliary materials such as nifedipine and the like, and the mixture is filled into a capsule and then coated outside the capsule. The selected capsule is a common HPMC capsule shell sold in the market, the capsule can be filled by a conventional capsule filling machine, and the capsule can be coated by a conventional high-efficiency coating pan. The preparation of the capsule can be completed by avoiding using a double-layer tablet press and a punching laser-beam drilling machine.

Drawings

FIG. 1 is a graph showing the release profiles of the drug from the microporous osmotic pump controlled release capsule of example 1 at different pH of the release medium.

FIG. 2 is a graph showing the release profile of a commercial formulation of the bisoxanide controlled release tablet at different pH release media.

Fig. 3 is a graph of mean blood concentration versus time for a bucindone controlled release tablet and a self-made microporous osmotic pump capsule.

FIG. 4 is a graph showing the release profiles of drugs from microporous osmotic pump capsules prepared without the addition of acid at various pH release media.

Figure 5 is a graph showing the effect of polyoxyethylene dosage on nifedipine release.

Detailed Description

The following examples are further illustrative of the present invention and are not intended to limit the scope of the present invention. The preparation can release nifedipine at an approximately constant drug release rate. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.

Example 1:

the prescription is shown in table 1(1000 granules):

table 1:

the preparation process comprises the following steps: 1. preparing capsules: heating and dissolving polyethylene glycol 6000 at 60-80 ℃, adding nifedipine, uniformly mixing, and cooling to obtain a nifedipine solid dispersion; grinding the yellow solid dispersion, and sieving with a 100-mesh sieve; mixing the solid dispersion powder, polyoxyethylene, citric acid, talcum powder and magnesium stearate, and filling into a hard capsule shell; 2. coating operation: weighing cellulose acetate and poloxamer 188 with the prescribed dosage, dissolving in acetone solution, placing the nifedipine capsule in a high-efficiency coating pan after the dissolution is finished, spraying the coating solution on the surface of the nifedipine capsule, and setting the condition of the coating pan as 18 (m) of blast volume³And/h), the atomization pressure is 1.6 +/-0.2 bar, the liquid spraying speed is 20 +/-1 g/min, the air inlet temperature is 45 +/-2 ℃, the material temperature is 28 +/-2 ℃, and after the liquid spraying is finished, the nifedipine microporous osmotic pump controlled release capsule is obtained by continuously drying in a coating pot. The weight of the coating is increased by 15 percent.

The measurement of the degree of release was carried out in the absence of light, and a sample of the preparation obtained in example 1 was taken, and a dissolution and release assay (third method of 0931, general rule) was carried out, wherein 900mL of 1% SDS solution was used as the release medium, the temperature (37 ± 0.5) ° c, the rotation speed was 50r/min, 5mL of nifedipine sample (n ═ 6) was taken, one piece was placed in each dissolution cup, and samples were taken at 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours, and 5mL of the dissolution medium was simultaneously replenished immediately after each sampling. The sample taken out is filtered by a 0.45 mu m water system microporous filter membrane, and the filtrate is taken out. The absorbance was measured at a wavelength of 238mn, and the release was calculated by substituting the absorbance into a standard curve. Meanwhile, a commercially available nifedipine controlled release tablet (biseparin, 30 mg/tablet) is used as a control. The release profiles of the sample of example 1 and the control sample in different pH media were measured by changing the pH of the release media, and the measurement results are shown in fig. 1 and fig. 2.

As can be seen from figures 1 and 2, compared with the original preparation, the nifedipine microporous osmotic pump controlled release capsule can release the medicine at a nearly constant speed. The drug release profiles in release media of different pH (1.2, 4.5, 6.8) were substantially identical.

EXAMPLE 2 pharmacokinetics study of nifedipine in microporous osmotic pump controlled release capsules

The 6 rabbits were randomly divided into two groups and fasted (free drinking) for 12 h before administration. The self-made microporous osmotic pump capsule (formula of example 1) and the commercially available nifedipine controlled release tablet (Bineway, 30 mg/tablet) were placed deep in the oral cavity of the rabbit, and swallowed intact. After administration, 0.5 mL of blood was collected in the ear margin vein at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 and 36 h, respectively, and immediately transferred to a heparin-treated centrifuge tube and centrifuged at 4000 rpm for 10 min. Separating plasma, and storing in refrigerator at-20 deg.C.

Precisely measuring 200 mu L of a plasma sample, placing the plasma sample in a 5mL centrifuge tube, adding 60 mu L of ammonia water, carrying out vortex oscillation for 2 min, adding 1.6 mL of anhydrous ether, carrying out vortex oscillation for 10 min, and centrifuging at 4000 rpm for 10 min. The organic phase was transferred to another centrifuge tube, dried in a 50 ℃ water bath, the residue redissolved with 100. mu.L of mobile phase, vortexed for 2 min and centrifuged at 6000 rpm for 5 min. HPLC-ultraviolet detection, methanol-water (70: 30) as mobile phase, 20 μ L injection.

Precisely weighing 25.0 mg of nifedipine raw material medicine, dissolving the nifedipine raw material medicine in methanol, metering the volume of the dissolved nifedipine raw material medicine into a 100 mL volumetric flask, and shaking the solution uniformly to obtain 250 mu g/mL mother liquor. Precisely measuring mother liquor in 2.0, 1.5, 1.0 and 0.5-25 mL volumetric flasks respectively, and shaking uniformly with methanol to constant volume to obtain nifedipine solutions of 20, 15, 10 and 5 mu g/mL. Precisely sucking 1 mL of 20 and 5 mu g/mL nifedipine solutions, diluting with methanol, and setting in a 10 mL volumetric flask to obtain 2.0 and 0.5 mu g/mL nifedipine solutions, further precisely sucking 1 mL of 0.5 mu g/mL nifedipine solution, diluting with methanol, and setting in a 10 mL volumetric flask to obtain 0.05 mu g/mL nifedipine solution.

Precisely measuring 200 muL of blank plasma in a centrifuge tube, respectively adding 20 muL of series standard solution, and preparing series plasma samples with the concentrations of 5, 50, 200, 500, 1000, 1500 and 2000 ng/mL. And (4) performing sample injection analysis according to the operation, and recording a chromatogram and a peak area. And (5) performing linear regression by taking the peak area of nifedipine as a vertical coordinate and the concentration of the blood sample as a horizontal coordinate for plotting. The linear regression equation obtained is A = 91.52C-317.6, R²= 0.998. The linear range is 5-2000 ng/mL.

The drug-time curves of the two formulations are compared in the following figure 3, and the Tmax of the commercially available nifedipine controlled release tablet is 8.67 h, and the average Cmax is 908.56 ng/mL. After oral administration of the microporous osmotic pump capsule, the average Tmax of the rabbits was 9.33 h and the average Cmax was about 842.03 ng/mL. The average relative bioavailability of the self-made microporous osmotic pump capsule to the same dosage of the commercial controlled release tablet is calculated by a single dose experiment and is determined by the area AUC under the blood concentration-time curve_0~tData calculation to obtain average F_x(T)= 109.16%。

Example 3 is formulated as shown in table 2(1000 capsules):

table 2:

the preparation process comprises the following steps: 1. preparing capsules: heating and dissolving polyethylene glycol 6000 at 60-80 ℃, adding nifedipine, uniformly mixing, and cooling to obtain a nifedipine solid dispersion; grinding the yellow solid dispersion, and sieving with a 100-mesh sieve; mixing the solid dispersion powder, polyoxyethylene, talcum powder and magnesium stearate, and filling into a hard capsule shell; 2. coating operation: weighing cellulose acetate and poloxamer 188 according to the prescription amount, dissolving in acetone solution, and dissolving the above nitrePlacing the nifedipine capsule in a high-efficiency coating pan, spraying the coating liquid on the surface of the nifedipine capsule, and setting the condition of the coating pan as 18 (m) of blast volume³And/h), the atomization pressure is 1.6 +/-0.2 bar, the liquid spraying speed is 20 +/-1 g/min, the air inlet temperature is 45 +/-2 ℃, the material temperature is 28 +/-2 ℃, and after the liquid spraying is finished, the nifedipine microporous osmotic pump controlled release capsule is obtained by continuously drying in a coating pot. The weight of the coating is increased by 15 percent.

Measurement of degree of Release in the dark, samples of the preparation obtained in example 3 were taken, and dissolution and release measurements (third method of 0931, general guidelines) were carried out by selecting release media of a hydrochloric acid solution at pH 1.2, an acetate buffer solution at pH 4.5, and a phosphate buffer solution at pH 6.8 (each prepared according to the 2015 year edition of Chinese pharmacopoeia), adding 1% SDS, examining release studies of the drug over 24 hours at a temperature of (37. + -. 0.5) DEG C and a rotation speed of 50r/min, taking nifedipine samples (n ═ 6), placing one tablet in each dissolution cup, sampling 5mL at 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours, and simultaneously supplementing 5mL of dissolution media immediately after each sampling. The sample taken out is filtered by a 0.45 mu m water system microporous filter membrane, and the filtrate is taken out. The absorbance was measured at a wavelength of 238mn, and the release was calculated by substituting the absorbance into a standard curve. The measurement results are shown in FIG. 4. The results show that the drug release behavior without adding citric acid preparation is obviously related to the pH value of the release medium. When the pH value is higher, the medicament release has a time lag phenomenon and is incomplete.

Example 4 is formulated as shown in table 3(1000 capsules):

table 3:

the preparation process comprises the following steps: 1. preparing capsules: heating and dissolving polyethylene glycol 6000 at 60-80 ℃, adding nifedipine, uniformly mixing, and cooling to obtain a nifedipine solid dispersion; grinding the yellow solid dispersion, and sieving with a 100-mesh sieve; the solid dispersion powders, talc and magnesium stearate were mixed and different amounts of polyoxyethylene (0, 10, 20, 30, 60 and 100 mg per capsule) were added to prepare osmotic pump capsules. 2. Coating operation: weighing the cellulose acetate and poloxamer 18 with the prescription amount8 dissolving in acetone solution, placing the nifedipine capsule in a high-efficiency coating pan after the dissolution is finished, spraying the coating solution on the surface of the nifedipine capsule, and setting the coating pan under the condition that the blast volume is 18 (m)³And/h), the atomization pressure is 1.6 +/-0.2 bar, the liquid spraying speed is 20 +/-1 g/min, the air inlet temperature is 45 +/-2 ℃, the material temperature is 28 +/-2 ℃, and after the liquid spraying is finished, the nifedipine microporous osmotic pump controlled release capsule is obtained by continuously drying in a coating pot. The weight of the coating is increased by 15 percent.

The release rate was measured by light-shielding, and a sample of the preparation obtained in example 4 was taken, and according to the dissolution rate and release rate measurement method (third method of 0931, general rule), the release medium was selected to be water, 1% SDS was added, and the release of the drug was examined over 24 hours at a temperature of 37 ± 0.5℃ and a rotation speed of 50r/min, and a nifedipine sample (n ═ 6) was taken, placed in each dissolution cup, and sampled for 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours for 5mL, and 5mL dissolution medium was simultaneously replenished immediately after each sampling. The sample taken out is filtered by a 0.45 mu m water system microporous filter membrane, and the filtrate is taken out. The absorbance was measured at a wavelength of 238mn, and the release was calculated by substituting the absorbance into a standard curve.

The amount of polyoxyethylene has a certain influence on the drug release. Without addition of polyoxyethylene, 10% of the drug can be released within 2 hours, and then the release is extremely slow, and only about 20% is released within 24 hours. As the amount of polyoxyethylene is increased to 20 mg, the total drug release amount is increased, and the release at the early stage is faster, 70% can be released in 12 hours, but only 82% can be released in 24 hours. When the dosage of the polyoxyethylene is increased to 30 mg, although the drug release degree is maximum, the release is complete within 16 h, and the expected slow release effect is not achieved. With the continuous increase of the dosage of the polyoxyethylene, the drug release rate is gradually slowed down until the drug release is in a uniform and slow trend when the dosage of the polyoxyethylene is 100 mg.

Claims

1. A nifedipine controlled release capsule is characterized in that the controlled release capsule is prepared by filling nifedipine, polyoxyethylene and organic acid into a capsule shell and coating the capsule shell with a coating; wherein the mass ratio of the nifedipine to the polyoxyethylene to the organic acid is as follows: nifedipine, polyoxyethylene and an organic acid are = 1-10: 1-30: 1-10, wherein the organic acid is at least one of tartaric acid, fumaric acid, malic acid and citric acid; the coating is prepared by mixing cellulose, a plasticizer and a pore-foaming agent, and the weight ratio of each component is as follows: cellulose, a plasticizer and a pore-forming agent = 10-50: 0-15: 1-25, and the weight of the coating is increased by 3-20% of that of the uncoated medicine-containing capsule.

2. A nifedipine controlled release capsule is characterized in that a capsule shell is filled with nifedipine, polyoxyethylene, organic acid, adhesive and osmotic pressure regulator, and the controlled release capsule is prepared by coating the capsule shell; wherein the nifedipine, the polyoxyethylene, the organic acid, the adhesive and the osmotic pressure regulator are in the following mass ratio: nifedipine, polyoxyethylene, an organic acid, an adhesive and an osmotic pressure regulator are = 1-10: 1-30: 1-10: 1-25: 0-30, and the organic acid is at least one of tartaric acid, fumaric acid, malic acid and citric acid; the coating is prepared by mixing cellulose, a plasticizer and a pore-foaming agent, and the weight ratio of each component is as follows: cellulose, a plasticizer and a pore-forming agent = 10-50: 0-15: 1-25, and the weight of the coating is increased by 3-20% of that of the uncoated medicine-containing capsule.

3. Nifedipine controlled release capsule according to claim 1 or 2, wherein the molecular weight of the polyoxyethylene is 100000-300000.

4. Nifedipine controlled release capsule according to claim 1 or 2, characterized in that the molecular weight of the polyoxyethylene is 150000 to 250000.

5. Nifedipine controlled release capsules according to claim 1 or 2, characterized in that the nifedipine is pre-treated to be micronized, to be prepared as a solid dispersion, or to be prepared as a cyclodextrin inclusion compound.

6. Nifedipine controlled release capsules according to claim 5, characterized in that the solid dispersion selects at least one of polyethylene glycols, povidone, polyols as an adjuvant.

7. Nifedipine controlled release capsule according to claim 1 or 2, characterized in that the cellulose is selected from cellulose acetate or ethyl cellulose; the plasticizer is at least one selected from glycerol, propylene glycol, polyethylene glycol, triethyl citrate, diethyl phthalate, triethyl glycerate and castor oil; the pore-forming agent is selected from at least one of sucrose, lactose, mannitol, polyethylene glycol, hypromellose, hydroxypropyl cellulose, poloxamer and povidone.

8. Nifedipine controlled release capsule according to claim 2, characterized in that the binder is selected from at least one of hypromellose, hydroxypropyl cellulose, povidone; the osmotic pressure regulator is at least one selected from sucrose, lactose, glucose, mannitol, sorbitol, fructose, sodium chloride, potassium chloride, sodium sulfate, sodium phosphate, and sodium dihydrogen phosphate.

9. A method for preparing the nifedipine controlled-release capsule of claim 2, which comprises the following steps:

(a) carrying out pretreatment on nifedipine;

10. The method for preparing a nifedipine controlled-release capsule according to claim 9, wherein the pretreatment is micronization of nifedipine, preparation of a solid dispersion of nifedipine, or preparation of cyclodextrin inclusion compound of nifedipine; the organic solvent is acetone or a mixture of acetone and isopropanol.