CN115919806A - Preparation method of GABA (Gamma-aminobutyric acid) sustained-release capsule - Google Patents
Preparation method of GABA (Gamma-aminobutyric acid) sustained-release capsule Download PDFInfo
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Abstract
The invention relates to a preparation method of GABA (Gamma-aminobutyric acid) sustained-release capsules, which belongs to the technical field of biological medicines and is characterized in that raw materials of GABA, lactose and microcrystalline cellulose are mixed with hydroxypropyl methylcellulose to obtain a first mixture; wet granulating the first mixture with water to obtain wet granules; drying the wet granules at a certain temperature to obtain dry granules; a portion of the dried granulation is coated with an enteric coating and filled into a capsule shell along with the remaining dried granulation. The invention utilizes the enteric coating to prolong the release time of GABA, can maintain the effective treatment blood concentration for a longer time after being absorbed into blood, can continuously relieve symptoms, is convenient to use, can reduce the times of taking medicines and improve the compliance, further prolongs the physiological functions of GABA, improving the sleep of organisms, relieving anxiety, reducing blood pressure and the like; the preparation method is simple, low in cost, high in yield and beneficial to large-scale production. The sustained-release capsule prepared by the invention has small change amplitude of the accumulative dissolution after being placed for a long time, has stable property and is easy to store for a long time.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to a preparation method of GABA (Gamma amino acid butyric acid) sustained-release capsules.
Background
Gamma-aminobutyric acid (GABA) in the chemical formula C 4 H 9 NO 2 It is a natural active amino acid, widely distributed in internal organs of animals and in various plants. Research shows that GABA has the effects of reducing blood pressure, regulating cerebral vessels, promoting acetylcholine synthesis, enabling brain cells to move vigorously, promoting brain tissue metabolism and recovering brain cell functions; also has effects in regulating arrhythmia, treating epilepsy, improving lipid metabolism, preventing arteriosclerosis, preventing skin aging, regulating hormone secretion, and relieving chronic diseases; in addition, it has a sweet taste similar to glutamic acid, can enhance food flavor, and plays an important role in central regulation of gastric acid secretion.
The present research shows that the ingestion of a certain amount of GABA has various physiological effects of improving the sleep quality of the organism, reducing the blood pressure and the like, and the GABA is often added into beverages and foods or prepared into health care products and medicines. The Chinese patent CN101507510B discloses a preparation method of a health food raw material, extracting an extracting solution rich in gamma-aminobutyric acid, coating the gamma-aminobutyric acid extracting solution into a micro-capsule core substance by using a natural encapsulation material to form a capsule membrane, using a natural colloid as an embedding wall material, and producing a gamma-aminobutyric acid sustained-release microcapsule by using an embedding method technology; the sustained-release microcapsule has long release time, slow onset time, complex preparation method and high cost, and can not quickly relieve symptoms. Chinese patent CN104922145B discloses a composition of gamma-aminobutyric acid and chitosan oligosaccharide and a preparation method and application thereof, wherein the composition is prepared by uniformly mixing the gamma-aminobutyric acid and the chitosan oligosaccharide, uniformly mixing mannitol, pregelatinized starch and sodium carboxymethyl starch, fully mixing the two uniformly, adding an ethanol solution of polyvinylpyrrolidone to prepare a soft material, sieving, granulating, drying, granulating and filling into empty capsules.
Therefore, there is a need to develop a new dosage form containing GABA to solve the above problems encountered in the prior art.
Disclosure of Invention
The invention aims to provide a preparation method of a GABA (Gamma-aminobutyric acid) sustained-release capsule, which has the advantages of quick response time, quick symptom relieving, long drug action time, continuous symptom relieving, good curative effect or health care effect, high stability, simple preparation method and low cost, and solves the problems of slow response time, incapability of quickly relieving symptoms, complex preparation method, high cost and poor stability in the prior art. In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a preparation method of GABA sustained-release capsules, which comprises the following steps:
the method comprises the following steps: mixing the raw material GABA, a filler and an adhesive to obtain a first mixture;
step two: wet granulating the first mixture with water to obtain wet granules;
step three: drying the wet particles at a certain temperature to obtain dry particles;
step four: a portion of the dried granulation is coated with an enteric coating and filled into a capsule shell along with the remaining dried granulation.
The enteric-coated particles are partially coated with the enteric-coated layer and then filled into the capsule shell together with the rest of the dry particles, wherein the particles without the enteric-coated layer can accelerate the onset time, and the particles coated with the enteric-coated layer can prolong the action time of the medicament, so that the two components are combined to be used for treating (protecting health) well, and the preparation method is simple, low in cost and easy for large-scale production. The water used in the second step can be purified water, distilled water and the like.
As an embodiment of the present invention, the filler comprises one or more of lactose, microcrystalline cellulose, dextrin, sorbitol, isomaltulose, mannitol, starch.
As an embodiment of the present invention, the binder includes one or more of hypromellose, methylcellulose, sodium carboxymethylcellulose, povidone K30, and hyprolose.
As an embodiment of the invention, the weight contents of the components in the first step and the second step are as follows: 40-60 parts of GABA (gamma-aminobutyric acid), 135-165 parts of filler, 45-55 parts of adhesive and 5-17 parts of water.
As an embodiment of the present invention, the filler comprises lactose and microcrystalline cellulose. Lactose is used as an excellent tablet filler, has no hygroscopicity, and has good fluidity and compressibility; the microcrystalline cellulose has good compressibility and strong binding force; the combination of the lactose and the microcrystalline cellulose has the advantages of improving the taste, reducing the content of the lactose, ensuring the hyperglycemia population to eat at ease, ensuring the flowability and compressibility of the materials, along with low price, low production cost and high production feasibility.
In one embodiment of the present invention, the weight content of the lactose is 45 to 55 parts; the weight content of the microcrystalline cellulose is 90-110 parts.
As an embodiment of the present invention, the binder is hypromellose. The hydroxypropyl methylcellulose is selected, so that the hydroxypropyl methylcellulose can play a role in adhesion and can also serve as a slow release framework to provide a slow release effect.
In one embodiment of the present invention, the drying temperature is 45 to 55 ℃, preferably 50 ℃.
As an embodiment of the invention, the moisture content of the dried granules is 2-3%. The significance of controlling the moisture content of the dried particles is to prevent the materials from being easy to adhere due to over-humidity and influence on stability due to long-term storage.
As an embodiment of the invention, the enteric coating is selected from Eudragit L30D-55, which has the advantages of convenient use and simple preparation operation.
In one embodiment of the present invention, the mass ratio of the enteric-coated dry particles to the enteric-coated dry particles is 1 to 3:1, preferably 2:1.
compared with the prior art, the invention has the following beneficial effects:
1. according to the invention, GABA is subjected to wet granulation and drying, then partial particles are coated with an enteric coating, and the GABA and dried particles which are not coated with the enteric coating are filled into a capsule shell together, the release time of the particles coated with the enteric coating is prolonged, so that the release time of GABA is prolonged by 2-3 hours, the blood concentration can be effectively treated for a long time after the GABA is absorbed into blood, the symptoms can be continuously relieved, the use is convenient, the medicine taking times can be reduced, the compliance is improved, the physiological functions of GABA, such as improving the sleep of an organism, relieving anxiety, lowering blood pressure and the like, are further prolonged; the dried quick-release particles which are not coated with the enteric coating are released quickly, the drug takes effect quickly, and the quick-release granules are beneficial to quickly relieving symptoms; the GABA sustained-release capsule has good curative effect on treatment or health care, has low lactose content and is suitable for people with hyperglycemia. The preparation method is simple, low in cost, high in yield and beneficial to large-scale production.
2. The invention mixes the raw materials GABA, the filling agent, the adhesive and the purified water, and each auxiliary material is selected and used with the advantages of wide application range and low cost. The sustained-release capsule prepared by the invention has small change amplitude of the accumulative dissolution after being placed for a long time, has stable property and is easy to store for a long time.
Drawings
FIG. 1 is the dissolution profile of example 1 in a method for preparing a GABA sustained-release capsule.
FIG. 2 is the dissolution profile of example 2 in a method for preparing a GABA sustained release capsule.
FIG. 3 is the dissolution profile of example 3 in a method for preparing a GABA sustained release capsule.
FIG. 4 is the dissolution profile of example 4 in a method for preparing a GABA sustained release capsule.
FIG. 5 is the dissolution profile of example 5 in a method for preparing a GABA sustained release capsule.
FIG. 6 is the dissolution profile of example 6 in a method for preparing a GABA sustained release capsule.
FIG. 7 is the dissolution profile of example 7 in a method for preparing a GABA sustained release capsule.
FIG. 8 is the dissolution profile of comparative example 1 in the preparation method of a GABA sustained-release capsule.
FIG. 9 is the dissolution profile of comparative example 2 in the preparation method of a GABA sustained-release capsule.
FIG. 10 is the dissolution profile of comparative example 3 in the preparation method of a GABA sustained-release capsule.
FIG. 11 is the dissolution profile of example 1 after standing for six months in the manufacturing process of a GABA sustained release capsule.
FIG. 12 is a dissolution curve of comparative example 3 after being left for six months in the manufacturing method of a GABA sustained-release capsule.
Detailed Description
The present invention is further described below with reference to examples, but the embodiments of the present invention are not limited thereto.
The equipment or other reagents/materials used in the examples are commercially available.
The dissolution rate is measured by 0931 dissolution rate and release rate measurement methods (the first method: basket method, the first method under the item of enteric preparation) in the Chinese pharmacopoeia (2020 edition).
The content and related substances of the invention are measured by a high performance liquid chromatograph.
Example 1
In this example, a method for preparing a GABA sustained release capsule is provided, said method comprising the steps of:
the method comprises the following steps: mixing 50 parts of GABA, 50 parts of lactose, 100 parts of microcrystalline cellulose and 50 parts of hydroxypropyl methylcellulose to obtain a first mixture;
step two: wet granulating the first mixture with 10 parts of purified water to obtain wet granules;
step three: drying the wet granules at 50 ℃ until the moisture content is 2.5% to obtain dry granules;
step four: two thirds of the dried granules were coated with an enteric coating made of Eudragit L30D-55 and filled into capsule shells together with the remaining dried granules. Taking part of the capsules as samples 1-6, carrying out dissolution test, firstly dissolving in 0.1mol/L HCl for 2h, and then dissolving in pH6.8 phosphate buffer solution for 45min, wherein the obtained related indexes are detailed in Table 1.
The dissolution test parameters were as follows:
(1) The method comprises the following steps: basket method; (2) rotation speed: 50rpm; (3) dissolution medium volume: 1000ml; (4) liquid taking/liquid supplementing volume: 10ml; (5) filtration membrane: 0.45um.
TABLE 1 index of dissolution obtained in example 1
Example 2
In this example, a method for preparing a GABA sustained release capsule is provided, said method comprising the steps of:
the method comprises the following steps: mixing 40 parts of GABA, 45 parts of lactose, 90 parts of microcrystalline cellulose and 45 parts of hydroxypropyl methylcellulose to obtain a first mixture;
step two: wet granulating the first mixture with 5 parts of purified water to obtain wet granules;
step three: drying the wet granules at 50 ℃ until the moisture content is 2.5% to obtain dry granules;
step four: two thirds of the dry granules were coated with an enteric coating made of Eudragit L30D-55 and filled into capsule shells together with the remaining dry granules. Taking part of the capsules as samples 1-6, carrying out dissolution test, firstly dissolving in 0.1mol/L HCl for 2h, and then dissolving in pH6.8 phosphate buffer solution for 45min, wherein the obtained related indexes are detailed in Table 2.
The dissolution test parameters were as follows:
(1) The method comprises the following steps: basket method; (2) rotation speed: 50rpm; (3) dissolution medium volume: 1000ml; (4) liquid taking/liquid supplementing volume: 10ml; (5) filtration membrane: 0.45um.
Table 2 index of dissolution obtained in example 2
Example 3
In this example, a method for preparing a GABA sustained release capsule is provided, said method comprising the steps of:
the method comprises the following steps: mixing 60 parts of GABA, 55 parts of lactose, 110 parts of microcrystalline cellulose and 55 parts of hydroxypropyl methylcellulose to obtain a first mixture;
step two: wet granulating the first mixture with 17 parts of purified water to obtain wet granules;
step three: drying the wet granules at 50 ℃ until the moisture content is 2.5% to obtain dry granules;
step four: two thirds of the dried granules were coated with an enteric coating made of Eudragit L30D-55 and filled into capsule shells together with the remaining dried granules. Taking part of the capsules as samples 1-6, performing dissolution test, dissolving in 0.1mol/L HCl for 2h, and dissolving in pH6.8 phosphate buffer solution for 45min to obtain the related indexes shown in Table 3.
The dissolution test parameters were as follows:
(1) The method comprises the following steps: basket method; (2) rotation speed: 50rpm; (3) dissolution medium volume: 1000ml; (4) liquid taking/liquid supplementing volume: 10ml; (5) filtration membrane: 0.45um.
Table 3 index of dissolution obtained in example 3
Example 4
In this example, a method for preparing a GABA sustained release capsule is provided, said method comprising the steps of:
the method comprises the following steps: mixing 50 parts of GABA (Gamma-aminobutyric acid), 50 parts of lactose, 100 parts of microcrystalline cellulose and 50 parts of hydroxypropyl methylcellulose to obtain a first mixture;
step two: wet granulating the first mixture with 10 parts of purified water to obtain wet granules;
step three: drying the wet granules at 45 ℃ until the moisture content is 3% to obtain dry granules;
step four: two thirds of the dry granules were coated with an enteric coating made of Eudragit L30D-55 and filled into capsule shells together with the remaining dry granules. Taking part of the capsules as samples 1-6, performing dissolution test, dissolving in 0.1mol/L HCl for 2h, and dissolving in pH6.8 phosphate buffer solution for 45min to obtain the related indexes shown in Table 4.
The dissolution test parameters were as follows:
(1) The method comprises the following steps: basket method; (2) rotation speed: 50rpm; (3) dissolution medium volume: 1000ml; (4) liquid taking/liquid supplementing volume: 10ml; (5) filtration membrane: 0.45um.
Table 4 index of dissolution obtained in example 4
Example 5
In this example, a method for preparing a GABA sustained release capsule is provided, said method comprising the steps of:
the method comprises the following steps: mixing 50 parts of GABA, 50 parts of lactose, 100 parts of microcrystalline cellulose and 50 parts of hydroxypropyl methylcellulose to obtain a first mixture;
step two: wet granulating the first mixture with 10 parts of purified water to obtain wet granules;
step three: drying the wet granules at 55 ℃ until the moisture content is 2% to obtain dry granules;
step four: two thirds of the dry granules were coated with an enteric coating made of Eudragit L30D-55 and filled into capsule shells together with the remaining dry granules. Taking part of the capsules as samples 1-6, carrying out dissolution test, firstly dissolving in 0.1mol/L HCl for 2h, and then dissolving in pH6.8 phosphate buffer solution for 45min, wherein the obtained related indexes are detailed in Table 5.
The dissolution test parameters were as follows:
(1) The method comprises the following steps: basket method; (2) rotation speed: 50rpm; (3) dissolution medium volume: 1000ml; (4) liquid taking/liquid supplementing volume: 10ml; (5) filtration membrane: 0.45um.
TABLE 5 index of dissolution obtained in example 5
Example 6
In this example, a method for preparing a GABA sustained release capsule is provided, said method comprising the steps of:
the method comprises the following steps: mixing 50 parts of GABA, 50 parts of lactose, 100 parts of microcrystalline cellulose and 50 parts of hydroxypropyl methylcellulose to obtain a first mixture;
step two: wet granulating the first mixture with 10 parts of purified water to obtain wet granules;
step three: drying the wet granules at 50 ℃ until the moisture content is 2.5% to obtain dry granules;
step four: one half of the dried granules were coated with an enteric coating made of Eudragit L30D-55 and filled into capsule shells together with the remaining dried granules. Taking part of the capsules as samples 1-6, performing dissolution test, dissolving in 0.1mol/L HCl for 2h, and dissolving in pH6.8 phosphate buffer solution for 45min to obtain the related indexes shown in Table 6.
The dissolution test parameters were as follows:
(1) The method comprises the following steps: basket method; (2) rotation speed: 50rpm; (3) dissolution medium volume: 1000ml; (4) liquid taking/liquid supplementing volume: 10ml; (5) filtration membrane: 0.45um.
TABLE 6 index of dissolution obtained in example 6
Example 7
In this example, a method for preparing a GABA sustained release capsule is provided, said method comprising the steps of:
the method comprises the following steps: mixing 50 parts of GABA, 50 parts of lactose, 100 parts of microcrystalline cellulose and 50 parts of hydroxypropyl methylcellulose to obtain a first mixture;
step two: wet granulating the first mixture with 10 parts of purified water to obtain wet granules;
step three: drying the wet granules at 50 ℃ until the moisture content is 2.5% to obtain dry granules;
step four: three quarters of the dry granules were coated with an enteric coating made of Eudragit L30D-55, and filled into capsule shells with the remaining dry granules. Taking part of the capsules as samples 1-6, performing dissolution test, dissolving in 0.1mol/L HCl for 2h, and dissolving in pH6.8 phosphate buffer solution for 45min to obtain the related indexes shown in Table 7.
The dissolution test parameters were as follows:
(1) The method comprises the following steps: basket method; (2) rotation speed: 50rpm; (3) dissolution medium volume: 1000ml; (4) liquid taking/liquid supplementing volume: 10ml; (5) filtration membrane: 0.45um.
TABLE 7 index of dissolution obtained in example 7
From tables 1 to 7, the cumulative dissolution rates of the phosphate buffer solutions of the examples 1 to 6 of the present invention at ph6.8 for 20min and later are all greater than 85% (the data is a little lower than 85% due to more added enteric coating components of the example 7), and the drug is still continuously released after 2h to 3h, and the drug has long action time and quick onset time, which is beneficial to quickly and continuously relieving symptoms. Among them, example 1 is the most preferable example of the present invention.
In example 1, the mean value of the cumulative dissolution rates in 0.1mol/L HCl solution is 31.3%, the mean value of the cumulative dissolution rates in pH6.8 phosphate buffer solution gradually increases with time, reaches more than 100% in 45min, and the RSD value is lower than that of example 2, so that example 1 is the most preferable example of the present invention.
In example 6, the average value of the cumulative dissolution rate in the phosphate buffer solution with pH6.8 reaches 99.6% in 45min because the proportion of the dry particles coated with the enteric coating is reduced, and the dissolution rate of the medicine is slightly accelerated compared with that of the medicine in example 1; example 7, the proportion of the dried granules coated with the enteric coating is increased, the average value of the cumulative dissolution rate in 0.1mol/L HCl solution is 24.1 percent, and the onset time of the medicament is slower than that of example 1, but the sustained release effect can also be realized. Therefore, the mass ratio of the enteric-coated dry particles to the enteric-coated dry particles is preferably 2:1.
comparative example 1
This comparative example provides a method for preparing a GABA ordinary capsule comprising the steps of:
the method comprises the following steps: mixing 50 parts of GABA, 50 parts of lactose, 100 parts of microcrystalline cellulose and 50 parts of hydroxypropyl methylcellulose to obtain a first mixture;
step two: wet granulating the first mixture with 10 parts of purified water to obtain wet granules;
step three: drying the wet granules at 50 ℃ until the moisture content is 2.5% to obtain dry granules;
step four: the whole dry granulate is directly filled into capsule shells together.
Taking part of the capsules as samples 1-6, carrying out dissolution test, directly dissolving in 0.1mol/L HCl for 30min, and obtaining related indexes which are detailed in Table 8.
The dissolution test parameters were as follows:
(1) The method comprises the following steps: basket method; (2) rotation speed: 50rpm; (3) dissolution medium volume: 1000ml; (4) liquid taking/liquid supplementing volume: 10ml; (5) filtration membrane: 0.45um.
TABLE 8 index of dissolution rate obtained in comparative example 1
From table 8, it can be seen that the preparation method described in comparative example 1 was used to prepare a normal release capsule, without enteric coating to coat the partially dried granules, which was substantially completely released within 5-20min in 0.1mol/L HCl solution, with an average 10min cumulative dissolution > 85%, and the drug was fast acting but short acting time, which was not good for sustained relief of symptoms.
Comparative example 2
This comparative example provides a method for preparing a GABA common capsule comprising the steps of:
the method comprises the following steps: mixing 50 parts of GABA (Gamma-aminobutyric acid), 50 parts of lactose, 100 parts of microcrystalline cellulose and 50 parts of hydroxypropyl methylcellulose to obtain a first mixture;
step two: wet granulating the first mixture with 10 parts of purified water to obtain wet granules;
step three: drying the wet granules at 50 ℃ until the moisture content is 2.5% to obtain dry granules;
step four: the whole dry granules were encapsulated with an enteric coating made of Eudragit L30D-55, which was then filled into capsule shells.
Taking part of the capsules as samples 1-6, carrying out dissolution test, firstly dissolving in 0.1mol/L HCl for 2h, and then dissolving in pH6.8 phosphate buffer solution for 45min, wherein the obtained related indexes are detailed in Table 9.
The dissolution test parameters were as follows:
(1) The method comprises the following steps: basket method; (2) rotation speed: 50rpm; (3) dissolution medium volume: 1000ml; (4) liquid taking/liquid supplementing volume: 10ml; (5) filtration membrane: 0.45um.
TABLE 9 index of dissolution obtained in comparative example 2
As can be seen from table 9, the sustained-release capsules prepared by the preparation method described in comparative example 2, which were coated with an enteric coating, released only about 40% in 0.1mol/L HCl solution for 2 hours and 15min before in ph6.8 phosphate buffer, although the action time was long, the drug onset time was slow and the therapeutic effect was weak.
Comparative example 3
The compound gamma-aminobutyric acid capsule is prepared by referring to CN104922145B, and the preparation method is as follows:
the method comprises the following steps: the prescription amount comprises the following components in percentage by weight: 25% of gamma-aminobutyric acid, 25% of chitosan oligosaccharide, 28% of mannitol, 15% of gelatinized starch, 5% of sodium carboxymethyl starch, 1% of ethanol solution of polyvinylpyrrolidone and 1% of magnesium stearate;
step two: respectively sieving gamma-aminobutyric acid, chitosan oligosaccharide, mannitol, pregelatinized starch and sodium carboxymethyl starch with a 100-mesh sieve, weighing according to the formula amount, and uniformly mixing the gamma-aminobutyric acid and the chitosan oligosaccharide to obtain mixed powder A for later use; uniformly mixing mannitol, pregelatinized starch and sodium carboxymethyl starch to obtain mixed powder B;
step three: mixing the mixed powder A and B completely, adding ethanol solution of polyvinylpyrrolidone to obtain soft material, sieving with 20 mesh sieve, granulating, oven drying at 50 deg.C, sieving with 18 mesh sieve, grading, adding magnesium stearate, mixing, and making into capsule.
Taking part of the capsules as samples 1-6, carrying out dissolution test, directly dissolving in 0.1mol/L HCl for 30min, and obtaining related indexes detailed in Table 10.
The dissolution test parameters were as follows:
(1) The method comprises the following steps: basket method; (2) rotation speed: 50rpm; (3) dissolution medium volume: 1000ml; (4) liquid taking/liquid supplementing volume: 10ml; (5) filtration membrane: 0.45um.
TABLE 10 index of dissolution rate measured by gamma-aminobutyric acid in comparative example 3
As can be seen from Table 10, comparative example 3 has a fast dissolution rate, dissolution is more than 85% in 10min, and release is almost complete in 20min, which shows that the product has a short action time compared with the product of the present patent.
The compound capsule obtained in the comparative example 3 and the sustained-release capsule obtained in the example 1 are placed for 6 months at the temperature of 40 +/-2 ℃ and the relative humidity of 75% +/-5%. Samples 1-6 were taken at the end of the 6 th month period of the test and were first dissolved in 0.1mol/L HCl for 2h and then in pH6.8 phosphate buffer for 45min, as determined by the dissolution determination method described in the context of the present invention. The obtained relevant indexes are detailed in Table 11 and Biao 12.
TABLE 11 indices of dissolution measured after six months of storage of the samples of example 1
TABLE 12 indexes of dissolution rates measured after the sample of comparative example 3 was left for six months
From table 11, the compound capsule obtained in comparative example 3 decreased in dissolution rate after standing for 6 months, with 30min > 85%, which was much smaller than the 10min dissolution > 85% immediately after preparation; the sustained-release capsule obtained in the patent example 1 has a small change range of dissolution rate after being placed for 6 months, and has a small decrease range compared with the sustained-release capsule just after preparation. The sustained-release capsule prepared by the method has more stable quality.
In conclusion, the cumulative dissolution rate of the invention is in the range of 24-51% after 2h in 0.1mol/L HCl solution, and in the range of 97-101% after 45min in pH6.8 phosphate buffer solution, the values are all superior to those of the comparative example, the drug has quick onset time while prolonging the release time of GABA, and is beneficial to quickly and continuously relieving symptoms.
Claims (10)
1. A preparation method of a GABA sustained-release capsule is characterized by comprising the following steps of:
the method comprises the following steps: mixing the raw material GABA, a filler and an adhesive to obtain a first mixture;
step two: wet granulating the first mixture with water to obtain wet granules;
step three: drying the wet granules at a certain temperature to obtain dry granules;
step four: a portion of the dried granulation is coated with an enteric coating and filled into a capsule shell along with the remaining dried granulation.
2. The method of claim 1, wherein: the filler comprises one or more of lactose, microcrystalline cellulose, dextrin, sorbitol, isomaltulose, mannitol, and starch.
3. The method of claim 1, wherein: the adhesive comprises one or more of hydroxypropyl methylcellulose, sodium carboxymethylcellulose, polyvidone K30 and hydroxypropyl cellulose.
4. The method according to any one of claims 1 to 3, wherein the weight content of each component in the first step and the second step is as follows: 40-60 parts of GABA (gamma-aminobutyric acid), 135-165 parts of filler, 45-55 parts of adhesive and 5-17 parts of water.
5. The method of claim 4, wherein: the filler includes lactose and microcrystalline cellulose.
6. The method of claim 5, wherein: the weight content of the lactose is 45-55 parts; the weight content of the microcrystalline cellulose is 90-110 parts.
7. The method of claim 4, wherein: the adhesive is hydroxypropyl methylcellulose.
8. The method according to any one of claims 1 to 7, wherein: the drying temperature is 45-55 ℃, and preferably 50 ℃; the moisture content of the dried granules is 2-3%.
9. The method according to any one of claims 1 to 7, wherein: the enteric coating is selected from Eudragit L30D-55 Eudragit.
10. The method according to any one of claims 1 to 7, wherein: the mass ratio of the dry particles coated with the enteric coating to the dry particles not coated with the enteric coating is 1-3: 1, preferably 2:1.
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Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005097079A2 (en) * | 2004-04-02 | 2005-10-20 | Impax Laboratories, Inc. | Controlled release dosage for gaba receptor agonist |
US20080181943A1 (en) * | 2005-08-19 | 2008-07-31 | Sanofi-Aventis | Combination of a long-acting hypnotic agent and a short-acting hypnotic agent and therapeutic use thereof |
CN101507510A (en) * | 2009-02-17 | 2009-08-19 | 安徽来福高科股份有限公司 | Preparation method of health-care food raw-material Y-aminobutyric acid |
CN102552107A (en) * | 2012-01-12 | 2012-07-11 | 刘光权 | Two-phase release preparation containing zolpidem or salt of zolpidem and preparation method thereof |
CN103127023A (en) * | 2013-03-01 | 2013-06-05 | 南京正宽医药科技有限公司 | Duloxetine hydrochloride enteric-coated tablet and preparation method |
CN103520136A (en) * | 2013-10-15 | 2014-01-22 | 天垚医药科技发展(上海)有限公司 | Montelukast sodium pulse capsule and preparation method thereof |
CN104922145A (en) * | 2015-05-25 | 2015-09-23 | 福州乾正药业有限公司 | Composition of gamma-aminobutyric acid and chitosan oligosaccharide, as well as preparation method and applications of composition |
CN110522736A (en) * | 2019-08-26 | 2019-12-03 | 华熙生物科技股份有限公司 | A kind of improvement sleep, the two-layer release-controlled tablet of beauty and preparation method |
CN112843002A (en) * | 2021-04-06 | 2021-05-28 | 南京纽邦生物科技有限公司 | Gamma-aminobutyric acid oral sustained-release dry suspension and preparation method thereof |
CN114259490A (en) * | 2021-12-23 | 2022-04-01 | 宁波玉健医药有限公司 | Melatonin preparation and preparation method thereof |
-
2022
- 2022-12-22 CN CN202211656820.7A patent/CN115919806A/en active Pending
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005097079A2 (en) * | 2004-04-02 | 2005-10-20 | Impax Laboratories, Inc. | Controlled release dosage for gaba receptor agonist |
US20080181943A1 (en) * | 2005-08-19 | 2008-07-31 | Sanofi-Aventis | Combination of a long-acting hypnotic agent and a short-acting hypnotic agent and therapeutic use thereof |
CN101507510A (en) * | 2009-02-17 | 2009-08-19 | 安徽来福高科股份有限公司 | Preparation method of health-care food raw-material Y-aminobutyric acid |
CN102552107A (en) * | 2012-01-12 | 2012-07-11 | 刘光权 | Two-phase release preparation containing zolpidem or salt of zolpidem and preparation method thereof |
CN103127023A (en) * | 2013-03-01 | 2013-06-05 | 南京正宽医药科技有限公司 | Duloxetine hydrochloride enteric-coated tablet and preparation method |
CN103520136A (en) * | 2013-10-15 | 2014-01-22 | 天垚医药科技发展(上海)有限公司 | Montelukast sodium pulse capsule and preparation method thereof |
CN104922145A (en) * | 2015-05-25 | 2015-09-23 | 福州乾正药业有限公司 | Composition of gamma-aminobutyric acid and chitosan oligosaccharide, as well as preparation method and applications of composition |
CN110522736A (en) * | 2019-08-26 | 2019-12-03 | 华熙生物科技股份有限公司 | A kind of improvement sleep, the two-layer release-controlled tablet of beauty and preparation method |
CN112843002A (en) * | 2021-04-06 | 2021-05-28 | 南京纽邦生物科技有限公司 | Gamma-aminobutyric acid oral sustained-release dry suspension and preparation method thereof |
CN114259490A (en) * | 2021-12-23 | 2022-04-01 | 宁波玉健医药有限公司 | Melatonin preparation and preparation method thereof |
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