CN111803462A - Pravastatin sodium enteric-coated tablet and preparation method thereof - Google Patents
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Abstract
The invention provides a pravastatin sodium enteric-coated tablet and a preparation method thereof, belonging to the technical field of medicinal preparations. The enteric-coated tablet is prepared by a direct tabletting method and comprises a tablet core and an outer enteric-coated layer; the tablet core comprises pravastatin sodium and pharmaceutically acceptable auxiliary materials; the weight of the enteric layer is increased by 2.0-10.0%. The disintegrating agent is a mixture of any one of dry starch, low-substituted cellulose, croscarmellose sodium, sodium carboxymethyl starch and povidone and aluminum magnesium silicate, and the mass ratio is 3:1-4: 1. Is beneficial to improving the stability of pravastatin sodium under the acid condition and promoting the absorption degree in the intestinal environment. The invention reduces the dosage of main medicines and toxic and side effects, but better improves the bioavailability in intestinal tracts and has stable property in storage period.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a pravastatin sodium enteric-coated tablet and a preparation method thereof.
Background
Pravastatin sodium, also known as pavalsartan and pravastatin, is a white crystalline powder chemical with the chemical name of 1,2,6,7,8,8 a-hexahydro-2-methyl-8- (2-methylbutanoyloxy) -1-naphthalene-3 ',5', 6-trihydroxyheptanoic acid sodium salt and the molecular formula of C23H36NaO7Is easy to dissolve in water and methanol, is dissolved in absolute ethyl alcohol and has a melting point of 171.2-173 ℃. The chemical formula is as follows:
pravastatin sodium is a competitive inhibitor of 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), which is the rate-limiting enzyme catalyzing the conversion of HMG-CoA into mevalonate in the early stage of cholesterol biosynthesis, and thus reversibly inhibits HMG-CoA reductase, thereby inhibiting cholesterol biosynthesis. Clinically, it is indicated for patients with primary hypercholesterolemia, which is still uncontrollable due to dietary restrictions, or combined with hypertriglyceridemia (type IIa and IIb), and is absorbed mainly through the duodenum.
The oral preparation of pravastatin sodium is mainly capsule (specification 5mg and 10mg), and the gastric soluble tablet is ordinary tablet, and has specifications of 10mg, 20mg and 40 mg. The main component of pravastatin sodium belongs to BCS III drugs, and has the properties of high dissolution and low permeability. The pH value has obvious influence on the stability of pravastatin, pravastatin is unstable under an acidic condition and is easy to convert in gastric acid, so that the bioavailability of pravastatin is reduced, the absolute bioavailability is only 17 percent by referring to the original preparation specification, and the pravastatin can strongly stimulate gastric mucosa after being taken for a long time to cause adverse reactions such as nausea, vomiting and the like. CN 103861117B discloses a pravastatin sodium dispersible tablet and a preparation method thereof, which adopts hydroxypropyl-beta-cyclodextrin hydrophobic cavity to include pravastatin sodium with lower solubility in water, improves the solubility and stability of the drug, promotes the release and absorption of the drug in vivo and improves the bioavailability. The adopted fillers are compressible starch, microcrystalline cellulose and mannitol; the disintegrant is selected from microcrystalline cellulose, croscarmellose sodium and low substituted hydroxypropyl cellulose.
The pravastatin sodium is sensitive to water and heat, and a product with satisfactory stability is not easily prepared by adopting a wet granulation process. The literature reports that in the interaction research of pravastatin sodium and common pharmaceutical excipients, the pravastatin sodium is compatible with mannitol to improve the stability of pravastatin tablets. For example, CN101732267B discloses a pravastatin sodium tablet, its use and preparation method. The tablet contains pravastatin sodium, mannitol (the mass ratio is 1: 7-1: 9) serving as a filler, alkalizer (the stability of the pravastatin tablet is further improved), adhesive, disintegrant and lubricant. The preparation method comprises the steps of uniformly mixing pravastatin sodium and an alkalizer, adding the filler mannitol, optionally simultaneously adding other fillers, uniformly mixing, adding the adhesive, the disintegrant and the lubricant, uniformly mixing, and directly tabletting. The alkalizer is selected from alkaline compoundsMagnesium oxideOne or more of aluminum oxide, alkali metal hydroxide, alkaline earth metal hydroxide, aluminum hydroxide and sodium carbonate. The mass portion ratio of the alkalizer to the pravastatin sodium is 1:60-60: 1. The disintegrating agent is selected from one or more of starch and derivatives thereof, cellulose and derivatives thereof, cross-linked polyvinylpyrrolidone, alginic acid and aluminum magnesium silicate, and preferably sodium carboxymethylcellulose.
The preparation method of the pravastatin sodium enteric-coated pellets of Hushensong and the like (2 nd 2010 of Chinese pharmacist) adopts an extrusion spheronization process and a fluidized bed coating method to prepare the pravastatin sodium enteric-coated pellets, optimizes a prescription by adopting orthogonal test design, and inspects the powder property of the pellets and the in-vitro release test of different coating weight-increasing pellets.
Disclosure of Invention
In order to overcome the problems that pravastatin sodium is unstable under an acidic condition, is easy to convert in gastric acid, has poor flowability and compressibility of raw materials and is difficult to meet the technical requirements of direct tabletting, the invention aims to provide a pravastatin sodium enteric-coated tablet which consists of a tablet core and an outer enteric coating layer, an isolating layer is not required between the tablet core and the enteric coating layer, the production efficiency is improved, the dissolution rate and the bioavailability are high, the treatment effect is good, and the adverse reaction is remarkably reduced.
The invention also aims to provide a preparation method of the pravastatin sodium enteric-coated tablet, which adopts a direct tabletting method.
The filler is a mixture of mannitol, microcrystalline cellulose and sodium alginate, wherein the mass ratio of the mannitol to the microcrystalline cellulose to the sodium alginate is 1-3:1-2: 1. After the mannitol and the sodium alginate are added, compared with the mannitol which is singly used, the stability of the pravastatin sodium can be improved, the defect of poor material particle fluidity is overcome, the tabletting production efficiency is improved, and the operation is easy.
Preferably, the filler is a mixture of mannitol, microcrystalline cellulose, sodium alginate, and the like in equal mass, and the stability is optimal at the ratio.
Meanwhile, the disintegrating agent adopted by the invention is a mixture of any one of low-substituted cellulose, croscarmellose sodium, sodium carboxymethyl starch and povidone and aluminum magnesium silicate, and the mass ratio is 3:1-4: 1. Is beneficial to improving the stability of pravastatin sodium under the acid condition and promoting the absorption degree in the intestinal environment. If the ratio is more than the above range, the degree of disintegration is decreased, and the disintegrated product is in the form of a large lump during the in vitro release process. Below this ratio, there is a problem of slight release in gastric acid.
The magnesium aluminum silicate is compared with other silicic acid products, such as calcium silicate, sodium silicate and magnesium silicate, wherein the calcium silicate causes the absorption degree of pravastatin sodium enteric-coated tablets in the intestinal environment to be reduced, possibly caused by incomplete disintegration, the magnesium silicate cannot improve the stability of pravastatin sodium under the acidic condition, the sodium silicate is added to cause sticking in the tabletting process, and the silicon dioxide is added in a small amount to be used as a lubricant.
In order to achieve the purpose, the invention adopts the following technical scheme:
a pravastatin sodium enteric tablet comprising: a tablet core and an outer enteric coating layer, wherein the tablet core comprises pravastatin sodium and pharmaceutically acceptable auxiliary materials.
The pharmaceutically acceptable auxiliary materials comprise a filler, a disintegrating agent, a lubricant and a pH regulator, and the weight ratio of the auxiliary materials to the pravastatin sodium is as follows:
pravastatin sodium: 50 portions of
Filling agent: 600 portions and 900 portions
Disintegrating agent: 75-125 parts
Lubricant: 10 portions of
50-80 parts of pH regulator.
Specifically, the filler is a mixture of mannitol, microcrystalline cellulose and sodium alginate in equal mass:
the disintegrating agent is any one or a mixture of several of dry starch, low-substituted cellulose, croscarmellose sodium, sodium carboxymethyl starch and povidone, and the mass ratio is 3:1-4: 1.
The lubricant is one or a mixture of more of magnesium stearate, talcum powder, colloidal silicon dioxide and calcium stearate.
The pH regulator is magnesium oxide.
The weight of the enteric layer is increased by 2.0-10.0%. The enteric solution adopted by the enteric layer is a mixture of 1000g of acrylic resin No. 2, 50ml of diethyl phthalate, 100ml of castor oil and 8050ml of tween-tween. The enteric coating solution contains castor oil which is a water-insoluble plasticizer and has good compatibility with the polyacrylic resin II which is an enteric coating material, and the raw material is effectively prevented from being damaged by an acidic coating material, so that an isolation layer is not required to be coated between the enteric layer and the tablet core, the preparation process is simplified, and the production cost is reduced.
The preparation method of the pravastatin sodium enteric-coated tablet comprises the following steps:
step one, preparation of a tablet core: the preparation comprises the following components in parts by weight: pravastatin sodium: 50 parts of a filler: 600 and 900 parts of disintegrating agent: 75-125 parts of lubricant: 10 parts of pH regulator and 100 parts of pH regulator, and uniformly mixing and tabletting to obtain the tablet core.
Step two, preparation of enteric coating: taking a mixture of 1000g of acrylic resin No. 2, 50ml of diethyl phthalate, 100ml of castor oil and 8050ml of tween-tween, and uniformly stirring to obtain the enteric coating solution.
Step three, coating of enteric coating: taking the pravastatin sodium tablet core prepared in the step one, coating the pravastatin sodium tablet core prepared in the step two to prepare an enteric coating layer, wherein the weight of the enteric coating layer is increased: 2.0 to 10.0 percent of pravastatin sodium enteric-coated tablets.
The invention has the following advantages:
(1) the mixture of microcrystalline cellulose, mannitol and sodium alginate in equal mass is used as a filler, so that the stability of the pravastatin sodium is improved, the defect of poor flowability of material particles is overcome, the production efficiency of direct tabletting is improved, and the operation is easy.
(2) The disintegrant is a mixture of any one of dry starch, low-substituted cellulose, croscarmellose sodium, sodium carboxymethyl starch and povidone and aluminum magnesium silicate, improves the stability of pravastatin sodium under an acidic condition, quickly disintegrates and uniformly releases in an intestinal tract, promotes the absorption degree in an intestinal environment, and has high bioavailability.
(3) The invention has better stability in an acceleration test.
(4) The specifications of the commercially available gastric soluble tablets comprise four specifications of 10mg, 20mg and 40mg, and the pravastatin sodium enteric-coated tablet provided by the invention is 5mg, so that the dosage is reduced, the stimulation to gastric mucosa is reduced, and the adaptability of patients is improved.
Description of the drawings:
FIG. 1 is a dissolution curve of a conventional pravastatin sodium tablet (trade name: pravastatin) of a comparative formulation;
FIG. 2 is the dissolution curve of pravastatin sodium enteric-coated tablet of example 1 of the present invention.
The specific implementation mode is as follows:
the technical solution of the present invention will be described with reference to the following specific examples:
the tablet cores of examples 1-4 are formulated as shown in table 1:
TABLE 1
The resulting tablet cores of examples 1-4 had a Material Carl index of less than 20%, an angle of repose of less than 30 deg., and good material flow properties.
Example 5 stability test
The stability of the accelerated test was examined using the sample of example 1 as an object, and the results are shown in table 2:
TABLE 2
The test results in table 2 show that the pravastatin sodium enteric-coated tablets in example 6 meet the requirements on the content and related substances after accelerated test for 6 months, the preparation product has good stability, and the storage period is preliminarily set to be 2.5 years.
EXAMPLE 6 dissolution test
The results of examining the dissolution curves of the pravastatin sodium enteric-coated tablets obtained by the present invention and the commercially available pravastatin sodium tablets (trade name: pravastatin) with the sample of example 1 are shown in FIG. 1.
Example 7 pharmacokinetic testing
The pharmacokinetic tests of the pravastatin sodium enteric-coated tablets obtained in the present invention and the commercially available pravastatin sodium tablets (trade name: pravastatin) were carried out by using the sample of example 1 as an examination object, and the results were as follows:
test formulations: pravastatin sodium enteric-coated tablets obtained in example 1 (specification: 10 mg/tablet);
reference drug: buy Shanghai Shi Guibao pharmaceutical Co., Ltd, Zhongmei (prasugu, specification: 10 mg/tablet);
20 healthy male subjects were selected, aged (23.2. + -. 1.2), aged (65.3. + -. 5.2) kg, tall (172.3. + -. 5.2) cm, and all subjects underwent medical history inquiry and physical examination before the experiment, and were normal in electrocardiogram, chest X-ray, liver function, kidney function, blood routine, urine routine examination, mental state, and the like. The subjects had no other medications taken 2 weeks prior to the trial and during the trial period, while smoking alcohol and caffeine-containing beverages were prohibited. The subject becomes a volunteer subject of the test after signing an informed consent book after fully knowing the purpose and the method significance of the test and the pharmacology and adverse reaction of the product.
20 subjects were randomly divided into 2 groups, and were administered with 5mg of the test preparation or 10mg of the reference drug for 2 cycles alternately, respectively, with a wash period of 1 week. The subjects were fasted 12 hours before the test after having a light dinner, and the test was made by oral administration of the test preparation or the reference drug at the time of 7 hours in the morning of the test day, with the test preparation dose of 5mg and the reference drug dose of 10mg, administered with 200mL of warm boiled water. The subject is forbidden to drink water within 2 hours after taking the medicine, the subject takes a meal uniformly within 4 hours after taking the medicine respectively, blood is collected for 5mL each time at 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10 and 12 hours before taking the medicine and after taking the medicine, the blood sample is anticoagulated by heparin, plasma is centrifugally separated, and the blood sample is stored in a refrigerator at minus 50 ℃ to be tested.
10 healthy subjects orally administered 10mg pravastatin sodium tablet (prasudine), time to peak after in vivo absorption (T)max) Is (1.1 +/-0.2) h, peak concentration of blood medicine (C)max) Is (67.5 + -39.4 ng/mL), area under the curve (AUC)0→tIs (106.5 +/-59.2) h.ng/mL, AUC0→infIs (118.1 +/-63.5) h.ng/mL, eliminates half-life (t)1/2) Is (1.9 +/-0.5) h.
10 healthy subjects orally take 5mg self-made pravastatin sodium enteric-coated tablets, and the peak time (T) after in vivo absorptionmax) Is (2.8 +/-0.4) h, peak concentration of blood medicine (C)max) Is (71.2 + -32.4 ng/mL), area under the curve (AUC)0→tIs (123.5 +/-62.7) h.ng/mL, AUC0→infIs (134.1 +/-67.2) h.ng/mL, eliminates half-life (t)1/2) Is (3.6 +/-0.8) h.
Mean relative bioavailability of the test formulations as AUC0→tCalculated as (116.0. + -. 21.2)%, as AUC0→infCalculated as (113.5 ± 19.8)%. The subject has no obvious adverse reaction when taking the test preparation and the reference medicament, but the experience of the subject feeding back the test preparation in the test is better.
The test result shows that after a subject takes the pravastatin sodium enteric-coated tablet with the specification of 5mg, the peak reaching time of 10mg is prolonged compared with that of a reference medicament, the half life is prolonged, and the bioavailability is improved.
Claims (6)
1. A pravastatin sodium enteric tablet is characterized by comprising: a tablet core and an outer enteric coating layer, wherein the tablet core comprises pravastatin sodium and pharmaceutically acceptable auxiliary materials; the pharmaceutically acceptable auxiliary materials comprise a filling agent, a disintegrating agent, a lubricating agent and a pH regulator;
the weight ratio of the pharmaceutically acceptable auxiliary materials to the pravastatin sodium is as follows:
pravastatin sodium: 50 portions of
Filling agent: 600 portions and 900 portions
Disintegrating agent: 75-125 parts
Lubricant: 10 portions of
pH regulator: 50-80 parts of
The filler is a mixture of mannitol, microcrystalline cellulose and sodium alginate, wherein the mass ratio of the mannitol to the microcrystalline cellulose to the sodium alginate is 1-3:1-2:1;
the disintegrant is a mixture of any one of low-substituted cellulose, croscarmellose sodium, sodium carboxymethyl starch and povidone and aluminum magnesium silicate.
2. The pravastatin sodium enteric tablet of claim 1, wherein the lubricant is one or a mixture of magnesium stearate, talc, colloidal silicon dioxide and calcium stearate; the pH regulator is magnesium oxide.
3. The pravastatin sodium enteric tablet of claim 1, characterized in that the filler is an equal mass mixture of mannitol, microcrystalline cellulose, sodium alginate.
4. The pravastatin sodium enteric tablet of claim 1, wherein the mass ratio of any one of the low-substituted cellulose, croscarmellose sodium, sodium carboxymethyl starch, and povidone to the magnesium aluminum silicate is 3:1 to 4: 1.
5. The pravastatin sodium enteric tablet of claim 1, wherein the weight of the enteric layer is increased by 2.0-10.0%; the enteric solution adopted by the enteric layer is a mixture of 1000g of acrylic resin No. 2, 50ml of diethyl phthalate, 100ml of castor oil and 8050ml of tween-tween.
6. The preparation method of pravastatin sodium enteric tablet as claimed in claim 1, which comprises the following steps:
step one, preparation of a tablet core: the preparation comprises the following components in parts by weight: pravastatin sodium: 50 parts of a filler: 600 and 900 parts of disintegrating agent: 75-125 parts of lubricant: 10 parts of pH regulator and 50-80 parts of pH regulator, uniformly mixing and tabletting to obtain a tablet core;
step two, preparation of enteric coating: taking a mixture of 1000g of acrylic resin No. 2, 50ml of diethyl phthalate, 100ml of castor oil and 8050ml of tween-tween, and uniformly stirring to obtain an enteric coating solution;
step three, coating of enteric coating: taking the pravastatin sodium tablet core prepared in the step one, coating the pravastatin sodium tablet core prepared in the step two to prepare an enteric coating layer, wherein the weight of the enteric coating layer is increased: 2.0 to 10.0 percent of pravastatin sodium enteric-coated tablets.
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| CN113768896A (en) * | 2021-10-28 | 2021-12-10 | 中国中医科学院中药研究所 | Gardenia duodenum positioning preparation for treating cholestatic liver disease |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5225202A (en) * | 1991-09-30 | 1993-07-06 | E. R. Squibb & Sons, Inc. | Enteric coated pharmaceutical compositions |
| WO2000033821A1 (en) * | 1998-12-07 | 2000-06-15 | Bristol-Myers Squibb Company | Enteric coated pravastatin bead formulation |
| US20030176502A1 (en) * | 2002-01-11 | 2003-09-18 | Jackie Butler | Pravastatin pharmaceutical formulations and methods of their use |
| EP1905431A1 (en) * | 2002-01-11 | 2008-04-02 | Circ Pharma Research and Development Limited | Pravastatin pharmaceutical formulations and methods of their use |
| US20100055173A1 (en) * | 2006-10-10 | 2010-03-04 | Adel Penhasi | Release of statins in the intestine |
| CN201727758U (en) * | 2010-07-19 | 2011-02-02 | 沈阳亿灵医药科技有限公司 | Pravastatin sodium enteric-coated tablet |
| US20140044784A1 (en) * | 2011-03-15 | 2014-02-13 | Boryung Pharmaceutical Co., Ltd | Combined formulation with improved stability |
| CN103861117A (en) * | 2014-03-18 | 2014-06-18 | 王洪安 | Pravastatin sodium dispersible tablets and preparation method thereof |
-
2020
- 2020-07-15 CN CN202010679063.XA patent/CN111803462A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5225202A (en) * | 1991-09-30 | 1993-07-06 | E. R. Squibb & Sons, Inc. | Enteric coated pharmaceutical compositions |
| WO2000033821A1 (en) * | 1998-12-07 | 2000-06-15 | Bristol-Myers Squibb Company | Enteric coated pravastatin bead formulation |
| US20030176502A1 (en) * | 2002-01-11 | 2003-09-18 | Jackie Butler | Pravastatin pharmaceutical formulations and methods of their use |
| EP1905431A1 (en) * | 2002-01-11 | 2008-04-02 | Circ Pharma Research and Development Limited | Pravastatin pharmaceutical formulations and methods of their use |
| US20100055173A1 (en) * | 2006-10-10 | 2010-03-04 | Adel Penhasi | Release of statins in the intestine |
| CN201727758U (en) * | 2010-07-19 | 2011-02-02 | 沈阳亿灵医药科技有限公司 | Pravastatin sodium enteric-coated tablet |
| US20140044784A1 (en) * | 2011-03-15 | 2014-02-13 | Boryung Pharmaceutical Co., Ltd | Combined formulation with improved stability |
| CN103861117A (en) * | 2014-03-18 | 2014-06-18 | 王洪安 | Pravastatin sodium dispersible tablets and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113768896A (en) * | 2021-10-28 | 2021-12-10 | 中国中医科学院中药研究所 | Gardenia duodenum positioning preparation for treating cholestatic liver disease |
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