CN112641742B - Sacubitril valsartan sodium sustained-release tablet and preparation method thereof - Google Patents
Sacubitril valsartan sodium sustained-release tablet and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Abstract
The invention belongs to the field of pharmaceutical preparations, and provides a Sacubitril valsartan sodium sustained-release tablet and a preparation method thereof. The Sha Kuba Valsartan sodium sustained-release tablet contains Sacuba Valsartan sodium, sustained-release materials, fillers and other pharmaceutical excipients. In the Sha Kuba trovasartan sodium sustained release tablet, sha Kuba trovasartan sodium accounts for 30-65% of the weight of the tablet core, sustained release materials account for 15-40% of the weight of the tablet core, filling agents account for 8-50% of the weight of the tablet core, and lubricating agents account for 0.1-8%. The film coating material accounts for 0-10% of the total weight of the tablet. The invention also discloses a preparation method of the Sha Kuba trovaisartan sodium sustained release tablet, and the Sha Kuba trovaisartan sodium sustained release tablet prepared by the method has sustained release characteristics, is beneficial to maintaining long-term and efficient blood concentration in vivo, and improves the therapeutic effect of the medicament.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a Sacubitril valsartan sodium sustained-release tablet and a preparation method thereof.
Background
Heart Failure (HF) is a syndrome of changes in cardiac function caused by myocardial damage, is the terminal manifestation of all cardiovascular diseases, and has a consistently poor therapeutic effect. Epidemiological investigations have shown that the prevalence of chronic HF in adults in our country is 1.61%, the hospitalization mortality rate accounts for 40% of the cardiovascular hospitalization mortality rate, which is higher than the overall cardiovascular disease mortality rate, and about 50% of HF patients die within 5 years after diagnosis, comparable to the mortality rate of malignant tumors. Clinically, the treatment of chronic heart failure should be combined with the mechanism of myocardial remodeling to delay and prevent the development of myocardial remodeling and reduce the clinical mortality, besides improving the symptoms of patients and improving the quality of life.
Sha Kuba trovasartan sodium (LCZ 696) is developed by Nowa company, is a breakthrough innovative medicine in the field of chronic heart failure treatment in recent years, is the first angiotensin receptor-enkephalinase inhibitor, and has dual action mechanisms. Valsartan inhibits RAAS, and Sha Kuba koji enters into the body and is metabolized into an active enkephalinase inhibitor LBQ657 under the action of liver enzyme, so that the valsartan has the effect of inhibiting enkephalinase. The medicine is approved in the United states and European Union by marketing in 2015, enters the Chinese market in 2017, and is currently recommended as a first-line treatment medicine for chronic HF by treatment guidelines of various countries.
5363 the chemical name of the sodium salt of trovasartan Sha Kuba is as follows: octadecasodium hexa (4- { [ (1S, 3R) -1- ([ 1,1 '-biphenyl) -4-ylmethyl) -4-ethoxy-3-methyl-4-oxobutyl ] amino } -4-oxobutanoic acid) hexa (N-pentanoyl-N- { [2' - (1H-tetrazol-5-yl) biphenyl-4-yl ] methyl } -L-valine) -water (1/15) having the following structure:
at present, the Sha Kuba trovasartan sodium preparation sold in China only has common tablets (50 mg, 100mg and 200mg specifications) of Nowa company, needs to be administrated 2 times a day, is easy to cause blood concentration fluctuation, and has poor patient compliance. The Sha Kuba trovasartan sodium is prepared into the sustained release tablet which is administrated once a day, so that the administration frequency can be reduced, the probability of missed administration and wrong administration of a patient is reduced, the compliance of the patient is improved, the blood concentration can be stabilized, the peak valley phenomenon caused by taking a quick release preparation is avoided, and the toxic and side effects of the medicine are reduced.
The invention has the name of Chinese patent No. CN 105748420B: a preparation method of LCZ696 sustained-release matrix tablets for treating heart failure is characterized in that hydroxypropyl methylcellulose is used as a sustained-release matrix material, and the sustained-release tablets are prepared by adopting a powder direct compression mode. The invention has the name of Chinese patent No. CN 105935358B: a Sacubitril valsartan sustained release preparation and a preparation method thereof are characterized in that hydroxypropyl methylcellulose is used as a sustained release framework material, a dry granulation mode is adopted to prepare sustained release tablets, and film coating is carried out.
However, how to provide a preparation method and a prescription suitable for various production and research and development conditions, especially a Sha Kuba trovalsartan sodium sustained-release tablet prepared by adopting wet granulation, is a problem to be solved by scientific researchers.
Disclosure of Invention
Aiming at the problems in the prior art, the invention aims to provide a Sacubitril valsartan sodium sustained release tablet and a preparation method thereof, and the Sha Kuba Valsartan sodium sustained release preparation prepared by the method is beneficial to maintaining long-term and efficient blood concentration in vivo and improving the drug treatment effect. The sustained-release matrix tablet prepared by the invention can be prepared by adopting a direct powder tabletting, wet granulation or dry granulation process, wherein the wetting agent or the solvent of the adhesive for preparing the sustained-release tablet by wet granulation is absolute ethyl alcohol, and the prepared sustained-release tablet has stable crystal form, good particle fluidity, simple and easily controlled operation, contribution to industrial production and wider popularization and application prospect, and is suitable for various production and research and development conditions.
The Sha Kuba Valsartan sodium sustained-release tablet contains Sacuba Valsartan sodium, sustained-release materials, fillers and other pharmaceutical excipients. In the Sha Kuba trovasartan sodium sustained release tablet, sha Kuba trovasartan sodium accounts for 30-65% of the weight of the tablet core, sustained release materials account for 15-40% of the weight of the tablet core, filling agents account for 8-50% of the weight of the tablet core, and lubricating agents account for 0.1-8%. The film coating material accounts for 0 to 10 percent of the total weight of the tablet.
The Sha Kuba trovasartan sodium sustained release tablet disclosed by the invention has the sustained release material selected from one or more of hydroxypropyl methylcellulose, sodium alginate, polyoxyethylene, carbomer, hydroxypropyl cellulose and sodium carboxymethyl cellulose. The hydroxypropyl methylcellulose is selected from low-viscosity hydroxypropyl methylcellulose with the viscosity of 5-120 centipoises, or high-viscosity hydroxypropyl methylcellulose with the viscosity of 2600-100000 centipoises, or a mixture of the low-viscosity hydroxypropyl methylcellulose and the high-viscosity hydroxypropyl methylcellulose mixed according to the proportion of 1: 5-5: 1.
The Sha Kuba trovasartan sodium sustained release tablet provided by the invention has the filling agent selected from one or more of anhydrous lactose, mannitol, microcrystalline cellulose, sorbitol and xylitol.
In the Sha Kuba trovasartan sodium sustained release tablet, the lubricant is selected from one or more of magnesium stearate, talcum powder, superfine silica gel powder and sodium stearyl fumarate.
The Sha Kuba trovaisartan sodium sustained release tablet provided by the invention is characterized in that the film coating material is Opadry.
The preparation method of the Sha Kuba trovasartan sodium sustained release tablet comprises wet granulation, direct powder compression and dry granulation.
The Sha Kuba trovasartan sodium sustained release tablet provided by the invention has a wet granulation process, which comprises the following steps:
(1) Uniformly mixing Sha Kuba and the sustained-release material with the filler;
(2) Adding wetting agent or adhesive to prepare wet granules, drying in an oven, and sieving with a 20-mesh sieve to complete granules;
(3) Adding lubricant, mixing, and tabletting to obtain sustained release tablet core;
(4) And performing film coating on the sustained-release tablet core.
The Sha Kuba trovasartan sodium sustained release tablet provided by the invention has a dry granulation process, which comprises the following steps:
(1) Uniformly mixing Sha Kuba and the trovasartan sodium, a filling agent, a slow release material and a lubricant;
(2) Preparing granules by using a dry granulating machine;
(3) Adding lubricant, mixing, and tabletting to obtain sustained release tablet core;
(4) And performing film coating on the sustained-release tablet core.
The Sha Kuba trovasartan sodium sustained release tablet provided by the invention has the advantages that the direct powder tabletting process comprises the following steps:
(1) Uniformly mixing Sha Kuba and the trovasartan sodium, a filling agent, a slow release material and a lubricant;
(2) Tabletting to obtain sustained-release tablet core;
(3) And performing film coating on the sustained-release tablet core.
The Sha Kuba trovasartan sodium sustained release tablet provided by the invention has the advantages that the sustained release tablet prepared by the wet granulation process is stable in crystal form and good in particle fluidity, and a solvent of a wetting agent or an adhesive is absolute ethyl alcohol.
The positive progress effects of the invention are as follows:
(1) The Sha Kuba trovasartan sodium sustained release tablet has a good sustained release effect, sha Kuba trovasartan and valsartan are released for 8 hours to be not less than 85%, two active ingredients are slowly released, and in vitro tests show sustained release characteristics.
(2) The invention can be prepared by adopting wet granulation tabletting, direct powder tabletting or dry granulation processes, the main component does not generate crystal transformation, the invention is suitable for various production and research and development conditions, the operation is simple and easy to control, and the invention is beneficial to industrial production.
(3) The tablet prepared by the invention can continuously, slowly and stably release the medicine within a certain time, and can keep effective blood concentration, thereby continuously and effectively treating heart failure and improving the compliance of patients.
Drawings
FIG. 1 is a graph of the in vitro cumulative release percentage of trovasartan sodium in sustained release tablets of example 1 Sha Kuba versus time;
FIG. 2 is a graph of the in vitro cumulative release percentage of trovasartan sodium in sustained release tablets of example 2 Sha Kuba versus time;
FIG. 3 is a graph of the in vitro cumulative release percentage versus time for the sustained release tablets of valsartan sodium from Sacubitril according to example 3;
FIG. 4 is a graph of the in vitro cumulative release percentage versus time for the sustained release tablets of valsartan sodium from Sacubitril according to example 4;
FIG. 5 is a graph of the in vitro cumulative release percentage of trovasartan sodium versus time for example 5 Sha Kuba;
FIG. 6 is a graph of the in vitro cumulative release percentage versus time for the sustained release tablet of trovasartan sodium of example 6 Sha Kuba;
FIG. 7 is a graph of the in vitro cumulative release percentage of trovasartan sodium versus time for the sustained release tablet of example 7 Sha Kuba;
FIG. 8 is a graph of the in vitro cumulative release percentage of trovasartan sodium in sustained release tablets of example 8 Sha Kuba versus time;
FIG. 9 is a graph of the in vitro cumulative release percentage of trovasartan sodium versus time for the sustained release tablet of example 9 Sha Kuba;
FIG. 10 is a graph of the in vitro cumulative release percentage of trovasartan sodium versus time for example 10 Sha Kuba;
FIG. 11 is a graph of the in vitro cumulative release percentage of trovasartan sodium versus time for example 11 Sha Kuba;
FIG. 12 is a graph of the in vitro cumulative release percentage of trovasartan sodium versus time for example 12 Sha Kuba;
FIG. 13 is a graph of the in vitro cumulative release percentage versus time for the sustained release tablet of trovasartan sodium of example 13 Sha Kuba;
FIG. 14 is a graph of the in vitro cumulative release percentage of trovasartan sodium versus time for example 14 Sha Kuba;
FIG. 15 is a graph of the in vitro cumulative release percentage of trovasartan sodium versus time for example 15 Sha Kuba;
FIG. 16 is a graph of the in vitro cumulative release percentage versus time for the sustained release tablet of trovasartan sodium of example 16 Sha Kuba;
figure 17 is a DSC overlay of sustained release tablets of example 1 and examples 17-19 Sha Kuba and a blank excipient and drug substance.
Detailed Description
The invention will be further explained and illustrated by means of examples. It should be understood that: the embodiments of the present invention are given for illustration only and not for limitation, and any simple modification of the present invention based on the technical solution of the present invention falls within the protection scope of the present invention.
Example 1
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 1 and example 3-Sha Kuba sustained release tablet of example 16 process for preparing trovasartan sodium:
(1) Weighing raw and auxiliary materials according to the prescription amount, and uniformly mixing by an equivalent progressive method to obtain premixed powder. Adding appropriate amount of anhydrous ethanol to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 2 hr, and sieving with 20 mesh sieve. Adding the lubricant according to the prescription amount, and uniformly mixing;
(2) Tabletting: a special-shaped die with the size of 19.5mm multiplied by 9.6mm is adopted, and the hardness is controlled to be 8-10kg;
(3) Coating with a film coat: the above core tablets were coated with opadry 00F220009-CN to a weight gain of 2%.
Example 1-method for determining the release of Sha Kuba sustained release tablet of valsartan sodium of example 16:
according to the second method of the determination method of the dissolution rate and the release degree of 0931 in the four general guidelines of the Chinese pharmacopoeia 2015 edition, sha Kuba trovaisartan sodium sustained release tablets are placed in a dissolution cup, 900mL of degassed pH6.8 phosphate buffer solution is used as a release medium, the rotating speed is 50rpm, the temperature is (37 +/-0.5) DEG C, the release medium is taken for 10mL, the same amount of fresh medium at the same time is supplemented, the release medium is respectively 1h,2h,4h,6h,8h,10h and 12h, the release medium is filtered through a 0.45 mu m microporous membrane, after the filtrate is diluted, the peak area is determined according to a high performance liquid chromatography, and the detection wavelength is 255nm; in addition, a proper amount of reference substance is precisely weighed, the cumulative release percentage is calculated by the same method, and the requirement is met.
Example 2
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The preparation process of the sabotary valsartan sodium sustained release tablet of the embodiment 2 comprises the following steps:
(1) Weighing raw and auxiliary materials according to the prescription amount, and uniformly mixing by an equivalent progressive method to obtain premixed powder. The premixed powder was then used to prepare granules using a dry granulator. Adding the lubricant according to the prescription amount, and uniformly mixing;
(2) Tabletting: a special-shaped die with the size of 19.5mm multiplied by 9.6mm is adopted, and the hardness is controlled to be 8-10kg;
(3) Coating with a film coat: the above tablet cores were coated with opadry 00F220009-CN at a weight gain of 2%.
The release rate of the Sacubitril valsartan sodium sustained release tablet of example 1 is shown in figure 1. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 2 is shown in figure 2. From the release curve it can be seen that: there was little difference in the release of valsartan and Sha Kuba koji indicating that the manufacturing process had little effect on the release of the tablets.
Example 3
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 4
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 5
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 6
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 7
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The release rate of the Sacubitril valsartan sodium sustained release tablet of example 3 is shown in figure 3. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 4 is shown in figure 4. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 5 is shown in figure 5. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 6 is shown in figure 6. The release rate of Sha Kuba sustained release tablets of trovasartan sodium of example 7 is shown in fig. 7. From the release curve it can be seen that: hydroxypropyl methylcellulose, sodium alginate, polyoxyethylene, carbomer, hydroxypropyl cellulose and sodium carboxymethylcellulose have slow release effects of different degrees. Wherein the carbomer with the strongest slow release effect is carbomer, and then sodium carboxymethylcellulose, hydroxypropyl cellulose, polyoxyethylene, hydroxypropyl methylcellulose and sodium alginate are sequentially used.
Example 8
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 9
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 10
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The release rate of the Sacubitril valsartan sodium sustained release tablet of example 8 is shown in figure 8. The release rate of the Sha Kuba trovalsartan sodium sustained release tablet of example 9 is shown in fig. 9. The release rate of Sha Kuba sustained release tablets of trovasartan sodium of example 10 is shown in fig. 10. From the release curve it can be seen that: the low-viscosity hydroxypropyl methyl cellulose, the high-viscosity hydroxypropyl methyl cellulose or the high-low-viscosity hydroxypropyl methyl cellulose are mixed for use, so that a good in-vitro slow release effect can be achieved.
Example 11
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 12
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The release rate of Sha Kuba sustained release tablets of trovasartan sodium of example 11 is shown in fig. 11. The release rate of Sha Kuba sustained release tablets of trovasartan sodium of example 12 is shown in fig. 12. From the release curve it can be seen that: the weight ratio of the high-viscosity and low-viscosity hydroxypropyl methylcellulose is related to the release speed and the release end point. If the ratio is too small, the early burst release of the medicine cannot be controlled; if the ratio is too large, the drug is not released and the therapeutic effect is not achieved.
Example 13
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 14
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The release rate of Sha Kuba sustained release tablets of trovasartan sodium of example 13 is shown in fig. 13. The release rate of Sha Kuba sustained release tablets of trovasartan sodium of example 14 is shown in fig. 14. From the release curve it can be seen that: the more the total dosage of the high-low viscosity hydroxypropyl methylcellulose is, the more obvious the slow release effect is.
Example 15
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 16
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The release rate of the Sha Kuba trovasartan sodium sustained release tablet of example 15 is shown in fig. 15. The release rate of the Sha Kuba trovasartan sodium sustained release tablet of example 16 is shown in fig. 16. As can be seen from the release profile: the type of filler has substantially no effect on the release of the drug.
Example 17
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Preparation process of Sha Kuba trovasartan sodium sustained release tablet of example 17:
(1) Weighing raw and auxiliary materials according to the prescription amount, and uniformly mixing by an equivalent progressive method to obtain premixed powder. Adding appropriate amount of water, making into soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 2 hr, and sieving with 20 mesh sieve. Adding the lubricant according to the prescription amount, and uniformly mixing;
(2) Tabletting: a special-shaped die with the size of 19.5mm multiplied by 9.6mm is adopted, and the hardness is controlled to be 8-10kg;
(3) Coating with a film coat: the above tablet cores were coated with opadry 00F220009-CN at a weight gain of 2%.
Example 18
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The preparation process of Sha Kuba trovasartan sodium sustained release tablet of example 18:
(1) Weighing raw and auxiliary materials according to the prescription amount, and uniformly mixing by an equivalent progressive method to obtain premixed powder. Adding appropriate amount of 50% ethanol to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 2 hr, and sieving with 20 mesh sieve. Adding the lubricant according to the prescription amount, and uniformly mixing;
(2) Tabletting: a special-shaped die with the size of 19.5mm multiplied by 9.6mm is adopted, and the hardness is controlled to be 8-10kg;
(3) Coating with a film coat: the above tablet cores were coated with opadry 00F220009-CN at a weight gain of 2%.
Example 19
(1) Core layer (per sheet):
(2) The film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Preparation process of Sha Kuba trovasartan sodium sustained release tablet of example 19:
(1) Weighing raw and auxiliary materials according to the prescription amount, and uniformly mixing by an equivalent progressive method to obtain premixed powder. Adding appropriate amount of 75% ethanol to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 2 hr, and sieving with 20 mesh sieve. Adding the lubricant according to the prescription amount, and uniformly mixing;
(2) Tabletting: a special-shaped die with the size of 19.5mm multiplied by 9.6mm is adopted, and the hardness is controlled to be 8-10kg;
(3) Coating with a film coat: the above tablet cores were coated with opadry 00F220009-CN at a weight gain of 2%.
The DSC overlay of example 1 and examples 17-19 and the blank excipients and drug substances is shown in FIG. 17. As can be seen from the figure: the crystal form of the sustained-release tablet prepared by using water, 50% ethanol and 75% ethanol as wetting agents is changed, and the crystal form of the sustained-release tablet prepared by using absolute ethanol as a wetting agent is not changed.
While the preferred embodiments and principles of this invention have been described in detail, it will be apparent to those skilled in the art that variations may be made in the embodiments based on the teachings of the invention and such variations are considered to be within the scope of the invention.
Claims (3)
1. A preparation method of a Sacubitril valsartan sodium sustained release tablet is characterized in that,
the preparation method of the Sha Kuba trovasartan sodium sustained release tablet is wet granulation;
the wet granulation process comprises the following steps:
(1) Uniformly mixing Sha Kuba trovalsartan sodium, a filling agent and a sustained-release material;
(2) Adding wetting agent or adhesive to prepare wet granules, drying in an oven, and sieving with a 20-mesh sieve to complete granules;
(3) Adding lubricant, mixing, and tabletting to obtain sustained release tablet core;
(4) Performing film coating on the sustained-release tablet core;
the tablet core of the sustained release tablet comprises the following components in percentage by weight: sha Kuba 30-65% of trovasartan sodium, 15-40% of slow release material, 8-50% of filling agent and 0.1-8% of lubricant;
the film coating material accounts for 2 to 10 percent of the total weight of the tablet;
the wetting agent or the adhesive solvent is absolute ethyl alcohol;
the slow release material is selected from one or more of hydroxypropyl methylcellulose, sodium alginate, polyoxyethylene, carbomer, hydroxypropyl cellulose and sodium carboxymethylcellulose;
the filler is selected from one or more of anhydrous lactose, mannitol, microcrystalline cellulose, sorbitol and xylitol;
the lubricant is selected from one or more of magnesium stearate, talcum powder, superfine silica gel powder and sodium stearyl fumarate.
2. The preparation method of Sha Kuba trovasartan sodium sustained release tablets according to claim 1, wherein the hydroxypropyl methylcellulose is selected from low viscosity hydroxypropyl methylcellulose with viscosity of 5-120 centipoise, high viscosity hydroxypropyl methylcellulose with viscosity of 2600-100000 centipoise, or a mixture of the two in a ratio of 1: 5 to 5: 1.
3. The method of preparing Sha Kuba trovasartan sodium sustained release tablets of claim 1, wherein the film coating material is opadry.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011621475.4A CN112641742B (en) | 2020-12-30 | 2020-12-30 | Sacubitril valsartan sodium sustained-release tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011621475.4A CN112641742B (en) | 2020-12-30 | 2020-12-30 | Sacubitril valsartan sodium sustained-release tablet and preparation method thereof |
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| CN113648284B (en) * | 2021-07-16 | 2022-11-11 | 南京海纳医药科技股份有限公司 | Tablet containing Sacubitril valsartan sodium and preparation method thereof |
| CN115444829B (en) * | 2022-10-25 | 2023-08-22 | 南京康川济医药科技有限公司 | Sakuba/valsartan sodium gastric retention sustained release tablet and preparation method thereof |
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