A nifedipine controlled-release tablet and its preparation method

Abstract

The present invention belongs to the field of pharmaceutical preparations, and particularly relates to a single-layer nifedipine controlled-release tablet and a preparation method thereof. The nifedipine controlled-release tablet of the present invention, through the ingenious combination of an effervescent disintegrant and conventional controlled-release tablet excipients, enables the active pharmaceutical ingredient to be released as much as possible by means of the thrust of the gas in the swollen tablet core. At the same time, the double-layer tablet is changed to a single-layer tablet, which only requires one-step granulation, simplifies the preparation process, improves the process stability, and is suitable for industrial application.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical preparations, and particularly relates to a single-layer nifedipine controlled-release tablet and a preparation method thereof. Background Art

[0002] Nifedipine's chemical name is dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, with a melting point of 171°C - 175°C, molecular formula C 17 H 18 N2O6, molecular weight 346.34, and the structural formula is as follows:

[0003]

[0004] The original research drug of nifedipine sustained (controlled)-release preparation was developed by Bayer AG of Germany. It has been developed to the third generation, with the trade name Adalat CC, which is the mainstream product in the current market. Although it has stable quality and relatively definite curative effect, there are still certain defects in the formulation and process of the preparation. Adalat CC is a double-layer controlled-release tablet. The boosting layer pushes the drug-containing layer through the drug release holes to achieve drug release. In order to achieve the drug release of the specified amount, the API is over-dosed, and the dosing amount is 110% of the specified amount; the preparation production process is complex. Polyethylene oxide has a low melting point, and the rotation of the paddle during the wet granulation process easily causes it to agglomerate. The heat between the punching dies during the tableting process easily causes sticking to the punch; it is difficult to use acetone to coat the controlled-release coating, which easily causes the tablet surface to turn white. Whitening reduces the accuracy of laser drilling in industrial production and even causes batch failures; in addition, the key excipient polyethylene oxide has a short shelf life of only 6 months, and the procurement cost of the manufacturer is relatively high.

[0005] Patent CN114748436B discloses a nifedipine composition and a preparation method thereof. Sodium alginate and sodium bicarbonate are added to the excipients, and the stability and sustained release of the nifedipine sustained-release tablet under light conditions are significantly improved through their combined use, and the preparation process is relatively simple. However, this preparation dissolves completely in only 12 hours, the patient's drug administration compliance is poor, and the drug concentration fluctuation in the body is relatively more risky than that of the original research drug.

[0006] Patent CN112870175B discloses a nifedipine composition with a formulation process similar to that of the original research drug, including a drug-containing layer and a boosting layer. The swelling material is polyethylene oxide, the osmotic agent is sodium chloride, and the binder is hypromellose. The controlled-release coating is made of cellulose acetate, and a release curve similar to that of Adalat CC can be achieved. The moisture-proof coating components are titanium dioxide, hydroxypropyl cellulose and hypromellose, and its light-shielding effect is not as good as that of the original research drug, and the light stability of the tablet is relatively poor. This preparation also uses a double-layer tablet core of a drug-containing layer and a boosting layer, and the preparation process is complex, which is prone to problems such as mixing of the two layers, mottled tablets and cracked tablets.

[0007] To overcome the above defects, the inventors attempted to change the bilayer tablets to monolayer tablets, screen suitable excipients, increase the drug release amount, reduce the excessive use of the active pharmaceutical ingredient, and improve the drug use safety. Summary of the Invention

[0008] In view of the deficiencies of the prior art, the inventors provide a new monolayer nifedipine controlled-release tablet with stable process and simple operation. Through the ingenious combination of an effervescent disintegrant and conventional controlled-release tablet excipients, with the thrust of the gas in the swollen tablet core, the active pharmaceutical ingredient is released as much as possible, and the finished preparation can achieve a zero-order drug release characteristic similar to that of the original research and release more completely.

[0009] The present invention is specifically realized through the following technical solutions:

[0010] A nifedipine controlled-release tablet, characterized in that it is composed of a tablet core, a controlled-release coat wrapped on the tablet core, and a light-shielding film coat.

[0011] Among them, the tablet core is composed of nifedipine, a penetrant, a thickening agent, a binder, a lubricant, and an effervescent disintegrant.

[0012] Preferably, the weight portion of nifedipine in the tablet core is 30-31.5 parts.

[0013] Preferably, the penetrant is selected from one or more of sodium chloride, potassium chloride, sorbitol, mannitol, xylitol, and maltitol; more preferably one or more of sodium chloride, sorbitol, and mannitol.

[0014] Preferably, the weight portion of the penetrant in the tablet core is 75-135 parts; more preferably 80-130 parts.

[0015] The thickening agent is selected from one or more of hydroxyethyl cellulose, hypromellose K100M, hypromellose K200M, and carbomer.

[0016] Preferably, the thickening agent is selected from one or more of hydroxyethyl cellulose L, hydroxyethyl cellulose M, hydroxyethyl cellulose G, hypromellose K100M, and hypromellose K200M.

[0017] Preferably, the weight portion of the thickening agent in the tablet core is 30-48 parts; further preferably 35-45 parts.

[0018] Preferably, the binder is selected from one or more of hypromellose, povidone, copovidone, and hydroxypropyl cellulose.

[0019] The weight portion of the binder in the tablet core is 1-25 parts; preferably 1-20 parts.

[0020] The lubricant contains one or more of magnesium stearate, sodium fumarate stearate, zinc stearate, calcium stearate, and stearic acid.

[0021] Preferably, the weight portion of the lubricant in the tablet core is 1 - 3 parts.

[0022] Preferably, the effervescent disintegrant is composed of an organic acid and a carbonate in a mass ratio of 1:2, wherein the organic acid includes but is not limited to one or more of citric acid and tartaric acid, and the carbonate includes but is not limited to one or more of sodium carbonate and sodium bicarbonate.

[0023] Preferably, the weight portion of the effervescent disintegrant in the tablet core is 5 - 15 parts.

[0024] The controlled-release coating includes a film-forming material and a pore-forming agent.

[0025] The film-forming material of the controlled-release coating is selected from one or more of ethyl cellulose, cellulose acetate, and polyvinyl resin; preferably, the weight portion of the film-forming material is 17 - 28 parts.

[0026] The pore-forming agent in the controlled-release coating includes at least one of polyethylene glycol and hydroxypropyl cellulose; preferably, the weight portion of the pore-forming agent is 15 - 25 parts.

[0027] Further, the solvent of the controlled-release coating solution is a 90% acetone aqueous solution; preferably, the solid content of the coating solution is 5.0% - 7.0%.

[0028] The light-shielding film coating is selected from at least one of Opadry gastro-resistant film coating premix; preferably, the light-shielding film coating is 8 - 14 parts.

[0029] Further, the solvent of the light-shielding film coating is purified water; preferably, the solid content of the coating solution is 10.0% - 15.0%.

[0030] The present invention also provides a preparation method of nifedipine controlled-release tablets, and the method includes the following steps:

[0031] (1) Mix the prescribed amount of nifedipine, penetrant, thickener, binder, and carbonate in the effervescent disintegrant; spray an appropriate amount of ethanol water for granulation;

[0032] (2) Dry the wet granules and screen them;

[0033] (3) Pass through a sieve, add the organic acid in the effervescent disintegrant, mix evenly; then add the lubricant and mix evenly;

[0034] (4) Press tablets;

[0035] (5) Dissolve the film-forming material and pore-forming agent in a solvent to prepare a controlled-release coating solution, and use the controlled-release coating solution to coat the tablet core;

[0036] (6) Use a laser drilling machine to drill a hole at the center position of one end of the long side of the tablet, with a hole diameter of 0.40 - 0.60 mm, preferably 0.50 mm, and the drilling depth should penetrate the controlled-release layer coating film;

[0037] (7) Dissolve the light-blocking film coating premix in a solvent to prepare a film coating solution, and use the film coating solution to coat the drilled tablet to obtain the nifedipine controlled-release tablet.

[0038] Compared with the prior art, the present invention has the following advantages:

[0039] (a) Greatly simplifies the preparation process and improves process stability. After changing the double-layer tablet to a single-layer tablet, only one-step granulation is required. Currently, commercially available nifedipine controlled-release tablets are all double-layer tablets, and the drug-containing layer and the boosting layer are granulated separately; the tablets of the present invention do not contain low glass transition temperature excipients, and there is no caking phenomenon during the processes such as mixing and granulation, and the risk of sticking to the punch during the tableting process is low. In addition, when pressing double-layer tablets, it is necessary to monitor the tablet weights of both the boosting layer and the drug-containing layer simultaneously, which requires a higher quality of the tablet press.

[0040] (b) The finished product quality is controllable, and the drug safety for patients is higher. Compared with double-layer tablets, the content control of the single-layer tablets of the present invention is more accurate, the overfeed amount is reduced, and the drug safety is improved to a certain extent; some industrial-grade laser drilling machines identify the drilling surface by color. When the double-layer tablets are coated with acetone, it is easy to cause the tablet surface to turn white and opaque, resulting in the drilling machine being unable to identify the tablet color or an increase in the error rate. The single-layer tablets of the present invention do not rely on color recognition for drilling, and the production process is smoother.

[0041] (c) Improves labor efficiency and saves production costs. Changing the two-step granulation to single-step granulation and the double-layer tableting to single-layer tableting doubles the production efficiency. The functional excipient polyoxyethylene in the original research tablets has a validity period of only 6 months, and the purchase cost for the manufacturer is relatively high. Description of the Drawings

[0042] Figure 1 is the dissolution curves of Examples 1 - 5 and the original research nifedipine controlled-release tablets;

[0043] Figure 2 is the dissolution curves of Comparative Examples 1 - 3 and the original research nifedipine controlled-release tablets. Detailed Embodiments

[0044] The beneficial effects of the present invention will be further described below through examples. It should be correctly understood that the examples of the present invention are only given for the purpose of illustrating the present invention, rather than limiting the present invention. Therefore, any simple improvement to the present invention under the premise of the method of the present invention falls within the scope claimed by the present invention.

[0045] Examples (prescription amount is calculated based on 1000 tablets)

[0046] Example 1

[0047] 1) Prescription

[0048]

[0049] 2) Preparation process

[0050] (a) Add the prescribed amounts of nifedipine, sorbitol, sodium chloride, hydroxyethyl cellulose G, hydroxyethyl cellulose L, copovidone, and sodium bicarbonate to a wet granulator and mix; spray in an appropriate amount of 90% ethanol-water solution to granulate.

[0051] (b) Add the wet granules to a fluidized bed, set the inlet air temperature at 50 ± 5 °C, dry until the loss on drying is ≤ 3.5% and then perform sieving.

[0052] (c) After sieving, add citric acid and mix for 20 min; then add magnesium stearate and mix for 3 min.

[0053] (d) Use an elliptical mold and compress the total mixed granules into tablets through a rotary tablet press, controlling the tablet hardness at 90 - 120 N.

[0054] (e) Dissolve cellulose acetate and hydroxypropyl cellulose in a 90% aqueous acetone solution and coat the tablet cores with a controlled-release layer.

[0055] (f) Use a laser drilling machine to drill holes at the center position of one end of the long side of the tablets, with a hole diameter of 0.40 - 0.60 mm and the drilling depth should penetrate the controlled-release layer coating film.

[0056] (g) Dissolve the film coating premix in purified water and coat the drilled tablets to obtain nifedipine controlled-release tablets.

[0057] Example 2

[0058] 1) Prescription

[0059]

[0060]

[0061] 2) Preparation process

[0062] (a) Add the prescribed amounts of nifedipine, mannitol, sodium chloride, hydroxyethyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and sodium bicarbonate to a wet granulator and mix; spray in an appropriate amount of 90% ethanol-water solution to granulate.

[0063] (b) Add the wet granules into a fluidized bed, set the inlet air temperature at 50 ± 5 °C, and dry until the loss on drying is ≤ 3.5%, then perform granulation sizing.

[0064] (c) After sieving is completed, add tartaric acid and mix for 20 min; then add zinc stearate and mix for 3 min.

[0065] (d) Use an elliptical mold and tablet the total mixed granules through a rotary tablet press, controlling the tablet hardness at 90 - 120 N.

[0066] (e) Dissolve cellulose acetate and hydroxypropyl cellulose in a 90% aqueous acetone solution and apply a controlled-release coating to the tablet core.

[0067] (f) Use a laser drilling machine to drill a hole at the center position of one end of the long side of the tablet, with a hole diameter of 0.40 - 0.60 mm, and the drilling depth should penetrate the controlled-release coating film.

[0068] (g) Dissolve the film coating premix in purified water and coat the drilled tablets to obtain nifedipine controlled-release tablets.

[0069] Example 3

[0070] 1) Prescription

[0071]

[0072]

[0073] 2) Preparation process

[0074] (a) Add the prescribed amounts of nifedipine, mannitol, sorbitol, hydroxyethyl cellulose, hydroxypropyl methylcellulose, and sodium bicarbonate into a wet granulator and mix; spray an appropriate amount of 90% ethanol-water solution for granulation.

[0075] (b) Add the wet granules into a fluidized bed, set the inlet air temperature at 50 ± 5 °C, and dry until the loss on drying is ≤ 3.5%, then perform granulation sizing.

[0076] (c) After sieving is completed, add citric acid and mix for 20 min; then add sodium fumarate stearate and mix for 5 min.

[0077] (d) Use an elliptical mold and tablet the total mixed granules through a rotary tablet press, controlling the tablet hardness at 90 - 120 N.

[0078] (e) Dissolve cellulose acetate, hydroxypropyl cellulose, and polyethylene glycol in a 90% aqueous acetone solution and apply a controlled-release coating to the tablet core.

[0079] (f) Use a laser drilling machine to drill a hole at the center position of one end of the long side of the tablet, with a hole diameter of 0.40 - 0.60 mm, and the drilling depth should penetrate the controlled-release coating film.

[0080] (g) Dissolve the film coating premix in purified water, and coat the punched tablets to obtain nifedipine controlled-release tablets.

[0081] Example 4

[0082] 1) Prescription

[0083]

[0084]

[0085] 2) Preparation process

[0086] (a) Add the prescribed amounts of nifedipine, sorbitol, hydroxyethyl cellulose, carbomer, copovidone, and sodium carbonate into a wet granulator for mixing; spray an appropriate amount of 90% ethanol-water for granulation.

[0087] (b) Add the wet granules into a fluidized bed, set the inlet air temperature at 50 ± 5 °C, dry until the loss on drying is ≤ 3.5%, and then perform sieving.

[0088] (c) After sieving, add citric acid and mix for 20 min; then add magnesium stearate and mix for 5 min.

[0089] (d) Use an elliptical mold, and press the total mixed granules into tablets through a rotary tablet press, controlling the tablet hardness at 90 - 120 N.

[0090] (e) Dissolve ethyl cellulose and polyethylene glycol in a 90% aqueous acetone solution, and coat the tablet cores with a controlled-release layer.

[0091] (f) Use a laser drilling machine to drill holes at the center position of one end of the long side of the tablets, with the hole diameter of 0.40 - 0.60 mm, and the drilling depth should penetrate the controlled-release layer coating film.

[0092] (g) Dissolve the film coating premix in purified water, and coat the punched tablets to obtain nifedipine controlled-release tablets.

[0093] Example 5

[0094] 1) Prescription

[0095]

[0096]

[0097] 2) Preparation process

[0098] (a) Add the prescribed amounts of nifedipine, sorbitol, potassium chloride, hydroxyethyl cellulose, hydroxypropyl cellulose, and sodium carbonate into a wet granulator for mixing; spray an appropriate amount of 90% ethanol-water for granulation.

[0099] (b) Add the wet granules into a fluidized bed, set the inlet air temperature at 50 ± 5 °C, and perform granulation after drying until the loss on drying is ≤ 3.5%.

[0100] (c) After sieving is completed, add tartaric acid and mix for 20 min; then add magnesium stearate and mix for 5 min.

[0101] (d) Use an elliptical mold and perform tabletting on the total mixed granules through a rotary tablet press, controlling the tablet hardness at 90 - 120 N.

[0102] (e) Dissolve hydroxypropyl cellulose and cellulose acetate in a 90% aqueous acetone solution, and perform controlled-release layer coating on the tablet core.

[0103] (f) Use a laser drilling machine to drill a hole at the center position of one end of the long side of the tablet, with the hole diameter of 0.40 - 0.60 mm and the drilling depth penetrating the controlled-release layer coating film.

[0104] (g) Dissolve the film coating premix in purified water, and perform coating on the drilled tablets to obtain nifedipine controlled-release tablets.

[0105] Comparative Example (prescription amount is calculated based on 1000 tablets)

[0106] Comparative Example 1

[0107] 1) Prescription

[0108]

[0109]

[0110] 2) Preparation process

[0111] (a) Add the prescribed amounts of nifedipine, sorbitol, potassium chloride, hydroxyethyl cellulose L, hydroxyethyl cellulose M, and copovidone into a wet granulator and mix; spray an appropriate amount of 90% ethanol water for granulation.

[0112] (b) Add the wet granules into a fluidized bed, set the inlet air temperature at 50 ± 5 °C, and perform granulation after drying until the loss on drying is ≤ 3.5%.

[0113] (c) After sieving is completed, add magnesium stearate and mix for 5 min.

[0114] (d) Use an elliptical mold and perform tabletting on the total mixed granules through a rotary tablet press, controlling the tablet hardness at 90 - 120 N.

[0115] (e) Dissolve ethyl cellulose and polyethylene glycol in a 90% aqueous acetone solution, and perform controlled-release layer coating on the tablet core.

[0116] (f) Use a laser drilling machine to drill a hole at the center position of one end of the long side of the tablet. The hole diameter is 0.40 - 0.60 mm, and the drilling depth should penetrate the controlled-release layer coating film.

[0117] (g) Dissolve the film coating premix in purified water and coat the drilled tablets to obtain nifedipine controlled-release tablets.

[0118] Comparative Example 2

[0119] 1) Prescription

[0120]

[0121]

[0122] 2) Preparation process

[0123] (a) Add the prescribed amounts of nifedipine, sorbitol, sodium chloride, hydroxyethyl cellulose G, hydroxyethyl cellulose L, and copovidone to a wet granulator and mix; spray in an appropriate amount of 90% ethanol-water solution to granulate.

[0124] (b) Add the wet granules to a fluidized bed, set the inlet air temperature at 50 ± 5 °C, dry until the loss on drying ≤ 3.5% and then perform sieving.

[0125] (c) After sieving, add sodium bicarbonate and citric acid and mix for 20 min; then add magnesium stearate and mix for 3 min.

[0126] (d) Use an elliptical mold and compress the total mixed granules into tablets through a rotary tablet press, controlling the tablet hardness at 90 - 120 N.

[0127] (e) Dissolve cellulose acetate and hydroxypropyl cellulose in a 90% aqueous acetone solution and coat the tablet cores with a controlled-release layer.

[0128] (f) Use a laser drilling machine to drill a hole at the center position of one end of the long side of the tablet. The hole diameter is 0.40 - 0.60 mm, and the drilling depth should penetrate the controlled-release layer coating film.

[0129] (g) Dissolve the film coating premix in purified water and coat the drilled tablets to obtain nifedipine controlled-release tablets.

[0130] Comparative Example 3

[0131] Refer to the prescription process in the original research formulation of nifedipine controlled-release tablets, Adalat, and prepare nifedipine controlled-release tablets.

[0132] 1) Prescription

[0133]

[0134]

[0135] 2) Preparation process

[0136] (a) Preparation of the drug-containing layer: Add the prescribed amounts of nifedipine, polyethylene oxide, and hypromellose E5 to a wet granulator for mixing; spray in an appropriate amount of 95% ethanol-water for granulation; add the wet granules to a fluidized bed and dry at 35°C. Pass the dried granules through a 20-mesh sieve, and mix the sieved dry granules with magnesium stearate to obtain the total mixed granules of the drug-containing layer.

[0137] (b) Preparation of the boosting layer: Add the prescribed amounts of polyethylene oxide, hypromellose E5, sodium chloride, and red iron oxide to a wet granulator for mixing; spray in an appropriate amount of 95% ethanol-water for granulation. Add the wet granules to a fluidized bed and dry at 35°C. Pass the dried granules through a 20-mesh sieve, and mix the sieved dry granules with magnesium stearate to obtain the total mixed granules of the boosting layer.

[0138] (c) Pour the total mixed granules of the drug-containing layer and the boosting layer into the hoppers of a double-layer tablet press respectively. First, press the drug-containing layer, and then press the boosting layer to form a double-layer tablet core.

[0139] (d) Semi-permeable membrane coating: Dissolve cellulose acetate and polyethylene glycol in a 90% aqueous acetone solution, and perform semi-permeable membrane coating on the tablet core.

[0140] (e) Laser drilling: Use a laser drilling machine to drill holes on the surface of the drug-containing layer, with a hole diameter of 0.8 mm ± 0.1 mm and a hole depth of 0.5 mm ± 0.1 mm.

[0141] (f) Film coating: Dissolve the prescribed amounts of hydroxypropyl cellulose, titanium dioxide, hypromellose, polyethylene glycol, and red iron oxide in purified water for film coating to obtain nifedipine controlled-release tablets.

[0142] Comparative Example 4

[0143] The prescription and preparation process are the same as those in Comparative Example 3, except that the dosage of nifedipine is reduced to 105% of the specification amount, i.e., 31.5 g.

[0144] Verification Example

[0145] 1. Uniformity of the controlled-dose unit in the tablet core

[0146] Sample and test the tablet cores of the examples and verification examples according to the "Technical Guidelines for the Study of Mixing Uniformity and Uniformity of Controlled-Dose Units in Oral Solid Preparations of Chemical Drugs (Trial)". Take samples 20 times during the tableting process, with at least 3 tablets measured each time.

[0147] Determine according to the high performance liquid chromatography method (General Principles 0512, Volume IV, Chinese Pharmacopoeia 2020 Edition). Operate under light protection.

[0148] Reference solution: Take nifedipine reference substance, weigh accurately, dissolve with methanol and quantitatively dilute to prepare a solution containing 0.4 mg of nifedipine per 1 ml. Measure an appropriate amount accurately and quantitatively dilute with the mobile phase to prepare a solution containing about 20 μg of nifedipine per 1 ml.

[0149] Chromatographic conditions: Use octadecylsilane chemically bonded silica gel as the filler; use methanol - water (60:40) as the mobile phase; the detection wavelength is 235 nm; the column temperature is 25 °C; the flow rate is 1 ml per minute, and the injection volume is 20 μl. The detection results are shown in Table 1.

[0150] Table 1. Detection results of the content uniformity of the controlled dose unit in the tablet core

[0151]

[0152] As can be seen from the above table, the content uniformity of the pressed single - layer tablets is more controllable than that of the double - layer tablets, the content of the product per unit dose is more accurate, and the safety of patients' medication is higher.

[0153] 2. Dissolution

[0154] Dissolution was determined according to the dissolution and release determination method (Method 2 of General Chapter 0931, Volume IV, Chinese Pharmacopoeia 2020 Edition), and the sample was placed in a sedimentation basket. Operate in the dark.

[0155] Dissolution conditions: Use 900 ml of phosphate - citrate buffer solution (pH 6.8) containing 0.5% sodium dodecyl sulfate (take 2.43 g of disodium hydrogen phosphate, 0.53 g of citric acid, dissolve in water and dilute to 1 L, adjust the pH value to 6.8 with phosphoric acid, add 5 g of sodium dodecyl sulfate, stir to dissolve, and shake well) as the dissolution medium, the rotation speed is 100 revolutions per minute, operate according to the law, and sample at 2, 4, 8, 12, 16, 20 and 24 hours respectively.

[0156] Limit: The dissolution amounts of each tablet of this product at 4, 12 and 24 hours should be 5% - 17%, 43% - 80% and more than 85% of the labeled amount respectively, and all should meet the requirements: within 4 - 8 hours, 8 - 12 hours and 12 - 16 hours, the average rate per hour should be 4% - 7% of the labeled amount. The detection results are shown in Table 2.

[0157] Table 2. Dissolution data of nifedipine controlled - release tablets at 37 °C in the standard medium

[0158]

[0159] As can be seen from the above table, the single-layer controlled-release tablets of the present invention can achieve a zero-order release dissolution curve similar to that of the original research. In the present invention, changing the addition method of the effervescent disintegrant or not adding it cannot make the drug achieve complete release. The two experimental data of the original research and Comparative Example 3 also show that there is obvious drug residue in the commercially available nifedipine osmotic pump controlled-release tablets Adalat, and it is necessary to over-dose, and the content reaches more than 110% to release 99-100%. Comparative Example 4 shows that when the feeding amount in the original research formula is reduced to 105%, the drug release amount can only reach 93.8%.

Claims

1. A nifedipine controlled-release tablet, characterized in that, It consists of a tablet core, a controlled-release coat wrapped around the tablet core, and a light-blocking film coat; wherein, the tablet core is composed of nifedipine, a penetrant, a thickening agent, a binder, a lubricant, and an effervescent disintegrant. The penetrant is selected from one or more of sodium chloride, potassium chloride, sorbitol, mannitol, xylitol, and maltitol, and the weight portion of the penetrant in the tablet core is 75 - 130 parts; the thickening agent is selected from one or more of hydroxyethyl cellulose, hypromellose K100M, hypromellose K200M, and carbomer, and the weight portion of the thickening agent in the tablet core is 30 - 48 parts; the binder is selected from one or more of hypromellose, polyvinylpyrrolidone, copolyvidone, and hydroxypropyl cellulose, and the weight portion of the binder in the tablet core is 1 - 25 parts; the effervescent disintegrant is composed of an organic acid and a carbonate with a mass ratio of 1:2, and the weight portion of the effervescent disintegrant in the tablet core is 5 - 15 parts; the controlled-release coat includes a film-forming material and a pore-forming agent; the film-forming material of the controlled-release coat is selected from one or more of ethyl cellulose, cellulose acetate, and polyvinyl acetate resin; the weight portion of the film-forming material is 17 - 28 parts; the pore-forming agent in the controlled-release coat includes one or both of polyethylene glycol and hydroxypropyl cellulose; the weight portion of the pore-forming agent is 15 - 25 parts; the preparation method of the nifedipine controlled-release tablet includes the following steps: (1) Mix the prescribed amounts of nifedipine, penetrant, thickening agent, binder, and the carbonate in the effervescent disintegrant; spray in an appropriate amount of ethanol water for granulation; (2) Dry the wet granules and screen them; (3) Pass through a sieve, add the organic acid in the effervescent disintegrant, mix evenly; then add the lubricant and mix evenly; (4) Press tablets; (5) Dissolve the film-forming material and the pore-forming agent in a solvent to prepare a controlled-release coating solution, and use the controlled-release coating solution to coat the tablet core; (6) Use a laser drilling machine to drill a hole at the center position of one end of the long side of the tablet, and the drilling depth should penetrate the controlled-release layer coating film; (7) Dissolve the light-blocking film coating premix in a solvent to prepare a film coating solution, and use the film coating solution to coat the drilled tablets to obtain nifedipine controlled-release tablets.

2. The nifedipine controlled-release tablets according to claim 1, characterized in that, The penetrant is selected from one or more of sodium chloride, sorbitol, and mannitol.

3. The nifedipine controlled-release tablets according to claim 1, characterized in that, The lubricant includes one or more of magnesium stearate, sodium fumarate stearate, zinc stearate, calcium stearate, and stearic acid.

4. The nifedipine controlled-release tablets according to claim 1, characterized in that, The organic acid includes one or more of citric acid and tartaric acid, and the carbonate includes one or both of sodium carbonate and sodium bicarbonate.

5. The nifedipine controlled-release tablets according to claim 1, wherein, The weight portion of nifedipine in the tablet core is 30 - 31.5 parts.

6. The nifedipine controlled release tablets according to claim 1, characterized in that, The weight portion of the penetrant in the tablet core is 80 - 130 parts; the weight portion of the thickening agent in the tablet core is 35 - 45 parts; the weight portion of the binder in the tablet core is 1 - 20 parts; the weight portion of the lubricant in the tablet core is 1 - 3 parts.

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