CN106176652B - Metformin hydrochloride sustained release tablet and preparation method thereof - Google Patents
Metformin hydrochloride sustained release tablet and preparation method thereof Download PDFInfo
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Abstract
The invention provides a metformin hydrochloride sustained-release tablet and a preparation method thereof, belonging to the field of pharmacy. The metformin hydrochloride sustained release tablet comprises metformin hydrochloride, an adhesive, an absorption enhancer, hydroxypropyl methylcellulose and pharmaceutic adjuvants, wherein the mass ratio of the metformin hydrochloride to the adhesive to the absorption enhancer is 500: 45-55: 2.5-3.5. The preparation method comprises the following steps: mixing the absorption enhancer, metformin hydrochloride and adhesive, granulating, mixing with hypromellose and medicinal adjuvants, and tabletting. The sustained release tablet can widen the absorption window of the metformin hydrochloride, has high bioavailability, and can ensure that the blood concentration of the metformin hydrochloride is relatively stably maintained at a treatment level for a long time, thereby effectively treating the disease. According to the preparation method, hypromellose is added after granulation, so that the slow release performance of the slow release tablet is greatly improved, and a better treatment effect is obtained.
Description
Technical Field
The invention relates to the field of pharmacy, and in particular relates to a metformin hydrochloride sustained-release tablet and a preparation method thereof.
Background
Metformin hydrochloride (metformin hydrochloride), chemical name: 1, 1-dimethylbiguanide hydrochloride of formula: c4H11N5HCl, molecular weight: 165.63, the chemical formula is as follows:
metformin hydrochloride is a biguanide oral hypoglycemic agent, is used for treating non-insulin dependent diabetes mellitus, and is an antidiabetic agent which can control the blood sugar level and improve macrovascular complications. Metformin hydrochloride has good hypoglycemic effect, can reduce the risk of blood fat and cardiovascular diseases, has the advantages of long-term medication safety, high cost performance and the like, and is widely recommended to be first-line medication of type II diabetes.
Metformin hydrochloride is a very water-soluble drug, the half-life period of a common oral preparation is short, and a large amount of repeated medication is needed to maintain the effective blood concentration (3 times a day, 500mg each time), which very easily causes great fluctuation of the blood concentration in vivo and causes adverse reaction. Therefore, in order to provide a sustained and stable blood concentration to better exert its hypoglycemic effect, a sustained-release formulation of metformin hydrochloride has been developed to increase patient compliance.
The regulation of Chinese pharmacopoeia indicates that the slow-release preparation is a preparation which is slowly released by oral medicines in a regulated release medium according to a requirement and at a non-constant speed, and compared with other corresponding ordinary preparations, the frequency of taking medicines every 24 hours is reduced from 3-4 times to 1-2 times.
With the development of high molecular materials, new polymers for medicinal use are increasing, and hydrophilic polymers are the most widely used ones. The polymer can swell in water, and the specific structure of the polymer can retain water and form a swelling hydrogel to retard the release of the drug. The most common sustained release dosage forms using hydrophilic polymers as blockers are hydrophilic gel matrix tablets, of which hydroxypropyl methylcellulose (HPMC) matrix tablets are representative. The skeleton type sustained release preparation can well solve the problem of drug burst release in the preparation process of the metformin hydrochloride sustained release preparation, so the existing metformin hydrochloride sustained release tablet is generally prepared by the skeleton type sustained release preparation process.
Metformin hydrochloride has an inherently weak permeability in the lower part of the gastrointestinal tract, which results in its absorption almost exclusively in the upper part of the gastrointestinal tract, and its oral bioavailability is also only 40-60% and decreases with increasing dosage, which means that it has some saturated absorption process, or absorption limited by the time of permeability. Metformin hydrochloride absorption is limited to the upper gastrointestinal tract and poorly absorbed in the distal small, large and colon, a limitation on absorption known as the "absorption window".
Chinese invention patent CN1295467A discloses a biphasic controlled release delivery system for highly water soluble drugs comprising an inner solid particulate phase and an outer solid continuous phase, wherein particles of the inner solid particulate phase are dispersed and embedded in the outer solid continuous phase. The inner solid particulate phase comprises a drug having high water solubility and a slow release material; the outer solid continuous phase comprises a slow release material. The technical proposal realizes the prolongation of the retention time of the drug stomach without depending on the combined medication of other drugs such as propantheline, thereby improving the bioavailability of the drug.
However, the metformin hydrochloride has certain stomach irritation, and some patients have adverse reactions of stomach discomfort. The technology improves the bioavailability of the metformin sustained-release tablet by increasing the residence time of the drug in the stomach, and increases the time of stomach discomfort and adverse reaction to a certain extent, so certain disadvantages still exist.
Disclosure of Invention
The first purpose of the present invention is to provide a metformin hydrochloride sustained release tablet, which can widen the absorption window of metformin hydrochloride, has high bioavailability, and can maintain the blood concentration of metformin hydrochloride at a therapeutic level relatively stably for a long time, thereby effectively treating the disease.
The second purpose of the invention is to provide a preparation method of the metformin hydrochloride sustained-release tablet, and hydroxypropyl methylcellulose is added after granulation in the preparation method, so that the sustained-release performance of the sustained-release tablet is greatly improved, and a better treatment effect is obtained.
In order to achieve the above purpose of the present invention, the following technical solutions are adopted:
the metformin hydrochloride sustained release tablet comprises metformin hydrochloride, an adhesive, an absorption enhancer, hydroxypropyl methylcellulose and pharmaceutic adjuvants, wherein the mass ratio of the metformin hydrochloride to the adhesive to the absorption enhancer is 500: 45-55: 2.5-3.5.
A preparation method of metformin hydrochloride sustained release tablet comprises mixing absorption enhancer, metformin hydrochloride and binder, granulating, mixing with hypromellose and medicinal adjuvants, and tabletting.
Generally, the gastrointestinal tract of the human body has an absorption limitation, i.e. an absorption window, for metformin hydrochloride. While the oral sustained-release delivery system in the prior art can release the carried metformin hydrochloride in a long time after administration, the oral sustained-release delivery system still has the problem of low bioavailability. This is mainly due to the fact that the common sustained release preparations in the prior art do not yet completely release the carried metformin hydrochloride in the gastrointestinal tract regions where metformin hydrochloride is well absorbed; when the sustained release preparation enters some regions where the metformin hydrochloride is poorly absorbed or non-absorbed, such as the distal small intestine, large intestine and colon, the sustained release preparation still releases the metformin hydrochloride contained therein and still has a higher proportion of metformin hydrochloride waiting to be released. The metformin hydrochloride released at this time has low absorption rate or even is not absorbed, resulting in low bioavailability of metformin hydrochloride, and blood concentration of metformin hydrochloride is lower than a therapeutic level for some time period, failing to effectively treat the disease.
Compared with the prior art, the invention has the beneficial effects that:
the sustained-release tablet can widen the absorption window of the metformin hydrochloride by controlling the proportion of the metformin hydrochloride, the adhesive and the absorption enhancer, and can keep a certain absorption rate in the area with weaker absorption of the metformin hydrochloride, thereby solving the problem of low bioavailability of the metformin hydrochloride caused by narrow absorption window on the basis of not increasing the uncomfortable reaction time of the stomach. The sustained-release tablet has high bioavailability, so that the blood concentration of the metformin hydrochloride is relatively stably maintained at a therapeutic level for a long time, thereby achieving an optimal level for treating the disease.
In addition, when the sustained release tablet is prepared, hydroxypropyl methylcellulose is a framework material, and the addition sequence of hydroxypropyl methylcellulose has a remarkable influence on the release performance of the sustained release tablet. The inventor finds that the sustained-release performance of the sustained-release tablet can be greatly improved compared with the method that hypromellose directly participates in the granulation process by adding hypromellose after granulation. The sustained-release tablet can be quickly released within a short time after the medicine is taken to enable the blood concentration to reach the treatment concentration, and then the release speed is slowed down to enable the blood concentration to be maintained at the treatment concentration for a long time, so that a better treatment effect is obtained.
Detailed Description
Embodiments of the present invention will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The embodiment provides a metformin hydrochloride sustained release tablet, which comprises metformin hydrochloride, an adhesive, an absorption enhancer, hypromellose and pharmaceutic adjuvants, wherein the mass ratio of the metformin hydrochloride to the adhesive to the absorption enhancer is 500: 45-55: 2.5-3.5, preferably 500: 50: 3.
by controlling the proportion of the metformin hydrochloride, the adhesive and the absorption enhancer, the sustained-release tablet can widen the absorption window of the metformin hydrochloride and keep a certain absorption rate in the area with weaker absorption of the metformin hydrochloride, thereby solving the problem of low bioavailability of the metformin hydrochloride caused by narrow absorption window on the basis of not increasing the uncomfortable reaction time of the stomach. The sustained-release tablet has high bioavailability, so that the blood concentration of the metformin hydrochloride is relatively stably maintained at a therapeutic level for a long time, thereby achieving an optimal level for treating the disease.
The content of the metformin hydrochloride in each sustained release tablet is 550mg, preferably 500 mg; the weight of each sustained release tablet is 1.01-1.10g, preferably 1.05 g.
The hydroxypropyl methylcellulose is a slow-release framework material, and is preferably the hydroxypropyl methylcellulose with the viscosity of 4000-100000 cps.
In a preferred embodiment of the present invention, the mass ratio of the total mass of metformin hydrochloride, the binder and the absorption enhancer to hypromellose is 11: 7-8. By controlling the total mass of the hypromellose, the metformin hydrochloride, the adhesive and the absorption enhancer, the sustained-release performance of the sustained-release tablet can be greatly improved, and the blood concentration of the sustained-release tablet can be maintained at the treatment concentration for a long time, so that a better treatment effect is obtained.
The binder comprises povidone and sodium carboxymethylcellulose. Povidone is a polymer having high adhesion and is used as a binder in the present invention, and povidone K30 is preferably used. Sodium carboxymethyl cellulose has binding and thickening properties. Preferably, the mass ratio of the povidone to the sodium carboxymethyl cellulose is 3: 1.2-2, most preferably, the mass ratio of the two is 3: 2. after a large number of experiments, the inventor proves that the sustained-release tablet prepared by mixing the povidone and the sodium carboxymethyl cellulose in the proportion as the adhesive has higher sustained-release performance than the sustained-release tablet prepared by singly using or mixing the povidone and the sodium carboxymethyl cellulose in other proportions.
The absorption enhancer comprises chitosan and calcium dihydrogen phosphate. The chitosan and the monocalcium phosphate are used as absorption promoters, and can promote the release amount of the carried metformin hydrochloride on the upper part of the gastrointestinal tract of the sustained-release tablet. Preferably, the mass ratio of the chitosan to the monocalcium phosphate is 1: 2-3, most preferably, the mass ratio of the two is 1: 2. after a large number of experiments, the inventor proves that the bioavailability of the prepared sustained-release tablet is higher when the chitosan and the calcium dihydrogen phosphate are mixed in the proportion than when the chitosan and the calcium dihydrogen phosphate are used independently or the chitosan and the calcium dihydrogen phosphate are mixed in other proportions.
The medicinal adjuvants include microcrystalline cellulose and magnesium stearate. Microcrystalline cellulose acts as a diluent, binder, and corrosion inhibitor, while also having lubricating and disintegrating effects. Magnesium stearate is used as a glidant, so that the tabletting process is favorably carried out.
Specifically, the sustained release tablet comprises the following raw materials in parts by weight:
50 parts of metformin hydrochloride, 2.8-3.7 parts of povidone, 1.4-2.1 parts of sodium carboxymethylcellulose, 0.08-0.11 part of chitosan, 0.19-0.23 part of monocalcium phosphate, 35-40 parts of hydroxypropyl methylcellulose, 9-11 parts of microcrystalline cellulose and 0.5-1.5 parts of magnesium stearate.
Wherein the mass ratio of the povidone to the sodium carboxymethyl cellulose is 3: 1.2-2; the mass ratio of the chitosan to the calcium dihydrogen phosphate is 1: 2-3.
Most preferably, the sustained release tablet comprises the following raw materials in parts by weight:
50 parts of metformin hydrochloride, 3 parts of povidone, 2 parts of sodium carboxymethylcellulose, 0.1 part of chitosan, 0.2 part of monocalcium phosphate, 38 parts of hydroxypropyl methylcellulose, 10 parts of microcrystalline cellulose and 1 part of magnesium stearate.
The sustained-release tablet prepared by adopting the raw materials with the proportion has better sustained-release performance and higher bioavailability, and has the best treatment effect on the non-insulin-dependent diabetes mellitus.
The embodiment also provides a preparation method of the metformin hydrochloride sustained-release tablet, which comprises the following steps:
a. mixing absorption enhancer, metformin hydrochloride and binder, and granulating.
Specifically, an absorption enhancer is used for preparing a solution A, and the concentration of the absorption enhancer in the solution A is 8-12%, preferably 10%; metformin hydrochloride and a binder are mixed uniformly, then mixed with the solution A and wet granulated, dried and granulated.
The absorption enhancer comprises chitosan and calcium dihydrogen phosphate; the binder comprises povidone and sodium carboxymethylcellulose.
Preferably, chitosan and monocalcium phosphate are first formulated into solution a with water.
Preferably, the metformin hydrochloride, the povidone and the sodium carboxymethylcellulose are respectively sieved by a 60-100 mesh sieve, preferably a 80 mesh sieve before being uniformly mixed, and then are mixed with the solution A after being uniformly mixed, and are granulated by a wet method, and dried at 40-60 ℃ and then granulated by 15-17 meshes, preferably dried at 50 ℃ and granulated by 16 meshes.
b. Mixing the obtained granule with hypromellose and medicinal adjuvants, and tabletting.
In addition, when the sustained release tablet is prepared, hydroxypropyl methylcellulose is a framework material, and the addition sequence of hydroxypropyl methylcellulose has a remarkable influence on the release performance of the sustained release tablet. The inventor finds that the sustained-release performance of the sustained-release tablet can be greatly improved compared with the method that hypromellose directly participates in the granulation process by adding hypromellose after granulation. The sustained-release tablet can be quickly released within a short time after the medicine is taken to enable the blood concentration to reach the treatment concentration, and then the release speed is slowed down to enable the blood concentration to be maintained at the treatment concentration for a long time, so that a better treatment effect is obtained.
The features and properties of the present invention are further described in detail below with reference to examples:
TABLE 1 raw materials for sustained-release tablets in examples 1 to 5 and comparative examples 1 to 10
Example 1
The present embodiment provides a metformin hydrochloride sustained release tablet, the raw materials of which are shown in table 1, and the preparation method of the sustained release tablet comprises:
a. preparing solution A with chitosan and calcium dihydrogen phosphate, mixing metformin hydrochloride, polyvidone and sodium carboxymethylcellulose, mixing with solution A, wet granulating, drying, and grading.
b. Mixing the obtained granule with hypromellose, microcrystalline cellulose and magnesium stearate, and tabletting.
Example 2
The present embodiment provides a metformin hydrochloride sustained release tablet, the raw materials of which are shown in table 1, and the preparation method of the sustained release tablet comprises:
a. preparing chitosan and calcium dihydrogen phosphate into a solution A with the concentration of 8 percent by using water; and then respectively sieving the metformin hydrochloride, the povidone and the sodium carboxymethylcellulose with a 100-mesh sieve, uniformly mixing, adding the solution A, performing wet granulation, drying at 60 ℃, and performing 15-mesh granulation to obtain granules.
b. Mixing the obtained granule with hypromellose, microcrystalline cellulose and magnesium stearate, and tabletting.
Example 3
The present embodiment provides a metformin hydrochloride sustained release tablet, the raw materials of which are shown in table 1, and the preparation method of the sustained release tablet comprises:
a. preparing chitosan and calcium dihydrogen phosphate into 10% solution A with water; and then respectively sieving metformin hydrochloride, povidone and sodium carboxymethylcellulose with a 80-mesh sieve, uniformly mixing, adding the solution A, performing wet granulation, drying at 50 ℃, and performing 16-mesh granulation to obtain granules.
b. Mixing the obtained granule with hypromellose, microcrystalline cellulose and magnesium stearate, and tabletting.
Example 4
The present embodiment provides a metformin hydrochloride sustained release tablet, the raw materials of which are shown in table 1, and the preparation method of the sustained release tablet comprises:
a. preparing chitosan and calcium dihydrogen phosphate into a solution A with the concentration of 12% by using water; and then respectively sieving metformin hydrochloride, povidone and sodium carboxymethylcellulose with a 60-mesh sieve, uniformly mixing, adding the solution A, performing wet granulation, drying at 40 ℃, and performing 17-mesh granulation to obtain granules.
b. Mixing the obtained granule with hypromellose, microcrystalline cellulose and magnesium stearate, and tabletting.
Example 5
This example provides a metformin hydrochloride sustained release tablet, the raw materials of which are shown in table 1, and the preparation method of which is the same as that of example 3.
Comparative example
The raw materials of the metformin hydrochloride sustained-release tablets provided in comparative examples 1 to 9 are shown in Table 1, and the preparation method thereof is in accordance with example 3.
Comparative example 10
The comparative example provides a metformin hydrochloride sustained release tablet, the raw materials of which are shown in table 1, and the preparation method of the sustained release tablet comprises the following steps:
a. preparing chitosan and calcium dihydrogen phosphate into 10% solution A with water; and then, respectively sieving metformin hydrochloride, povidone, sodium carboxymethylcellulose and hydroxypropyl methylcellulose with a 80-mesh sieve, uniformly mixing, adding the solution A, performing wet granulation, drying at 50 ℃, and finishing granules with 16 meshes to obtain granules.
b. Mixing the obtained granule with microcrystalline cellulose and magnesium stearate, and tabletting.
Experimental example 1
The metformin hydrochloride sustained release tablets provided in the examples of the present invention were evaluated in terms of the release rate by combining experiments as follows.
The metformin hydrochloride sustained-release tablets prepared in example 3 and comparative examples 1 to 5 and 10 were measured for their release rate according to the release rate measurement method (first method in appendix X D of the second part of the 2010 edition of the Chinese pharmacopoeia). The second method of dissolution was performed using 1000mL of phosphate buffer (pH 6.8) as the dissolution medium and at a rotation speed of 1000 rmp. Operating according to the method, respectively taking 10mL of solution when dissolving for 1h, 3h, 5h, 7h and 10h, filtering, precisely taking 3mL, 1mL and 1mL of subsequent filtrate, respectively placing in 100mL, 50mL and 100mL measuring bottles, adding phosphate buffer solution (pH 6.8) to dilute to scale, and shaking uniformly to obtain a sample solution; an appropriate amount of metformin hydrochloride control was also precisely weighed, dissolved in phosphate buffer (pH 6.8) and quantitatively diluted to a solution containing 5. mu.g per 1mL, as a control solution. Finally, the absorbance of the test solution and the absorbance of the reference solution are respectively measured at the wavelength of 232nm by adopting an ultraviolet-visible spectrophotometry (appendix IV A of the second part of the 2010 version of the Chinese pharmacopoeia), and the cumulative release amount of the metformin hydrochloride in different time periods is calculated. The results are shown in table 2:
TABLE 2 Release measurement results
As can be seen from Table 2, the release in the artificial intestinal juice is stable in example 3, i.e. within 1 hour, the release speed of the sustained release tablet is fast, so that the blood concentration of the metformin hydrochloride can rapidly reach the treatment concentration in a short time; then the sustained release tablet slowly and stably releases the medicament, so that the blood concentration of the metformin hydrochloride can be kept at the treatment concentration for a long time, and the curative effect is improved.
In contrast, the sustained-release tablets prepared in comparative examples 1 to 5 have uneven drug release performance, for example, the sustained-release tablets prepared in comparative example 1 and comparative example 2 have burst release within 1 hour; the sustained release tablets prepared in comparative examples 3 and 5 and comparative example 10 released less drug within 1h and did not reach therapeutic concentration; the sustained-release tablet prepared in the comparative example 4 releases drug slowly within 3-10h, can not maintain the blood concentration at the treatment concentration and has poor treatment effect.
From this, the mass ratio of povidone to carboxymethylcellulose is 1: 2-3, the metformin hydrochloride sustained release tablet in the prepared sustained release tablet is beneficial to stable drug release, quick response, long action time and good curative effect. In addition, by comparing the release rates of the sustained-release tablets prepared in example 3 and comparative example 10, it can be found that whether hypromellose participates in granulation or not has a significant influence on the release performance of the finally prepared sustained-release tablets. Experiments prove that the sustained-release tablet prepared by mixing the granulated material and the hydroxypropyl methylcellulose has the best sustained-release performance.
Test example 2
The sustained release metformin hydrochloride tablets provided in the examples of the present invention were evaluated in terms of bioavailability by the following tests.
The products prepared in example 3 and comparative examples 6 to 9 were used as test drugs and marketed products (
XR lattice waling, note: prepared by the method of the aforementioned patent CN 1295467A) as a reference formulation for relative bioavailability test studies.
120 healthy male subjects were selected and received no other medications 2 weeks prior to the test and during the test period. The groups were randomly divided into 6 groups, designed using a double crossover test, with a wash period of 7 days. Each group of 20 subjects was randomly divided into 2 groups, and each group of subjects were administered test drugs and reference preparations alternately over different study periods. The subjects were deprived of water for 2 hours after dosing and had a meal at once after 4 hours of fasting. During the test period, smoking and drinking, caffeine-containing drinks and strenuous exercise were prohibited.
Blood sampling time: taking blood from upper limb vein at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hr before and after administration, 3.5mL each time, centrifuging, and freezing.
The concentration of metformin in plasma is used as a determination index (HPLC-UV method determination), and the AUC is calculated by adopting a trapezoidal integration method0-24、AUCSSEvaluation of each group of test drugs by area method against a reference preparation (
XR lattice walnuts) relative bioavailability. The results are shown in Table 3:
TABLE 3 relative bioavailability assay results
As can be seen from Table 2, the sustained-release tablets prepared in example 3 showed a difference in metformin hydrochloride from the marketed product (A)
XR glauber) was 112% more bioavailable than the marketed product. Whereas the bioavailability (77-92%) of metformin hydrochloride in the sustained-release tablets prepared in comparative examples 6-9 was much lower than that of example 3. Thus, the mass ratio of chitosan to monocalcium phosphate is 1: 2-3, the bioavailability of the metformin hydrochloride in the prepared sustained-release tablet can be improved, so that the drug effect is improved.
In addition, the sustained release tablets provided in examples 1, 2, 4 and 5 of the present invention have similar release and bioavailability as example 3, and are not listed one by one.
While particular embodiments of the present invention have been illustrated and described, it would be obvious that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.
Claims (4)
1. The metformin hydrochloride sustained release tablet is characterized by comprising metformin hydrochloride, an adhesive, an absorption enhancer, hypromellose and pharmaceutic adjuvants, wherein the mass ratio of the metformin hydrochloride to the adhesive to the absorption enhancer is 500: 45-55: 2.5-3.5;
the adhesive is prepared from the following components in percentage by mass of 3: 1.2-2 of povidone and sodium carboxymethylcellulose;
the absorption enhancer comprises the following components in a mass ratio of 1: 2-3 of chitosan and monocalcium phosphate;
the mass ratio of the total mass of the metformin hydrochloride, the adhesive and the absorption enhancer to the hypromellose is 11: 7-8;
the pharmaceutical excipients comprise microcrystalline cellulose and magnesium stearate.
2. The metformin hydrochloride sustained-release tablet according to claim 1, wherein the sustained-release tablet comprises the following raw materials in parts by weight:
50 parts of metformin hydrochloride, 2.8-3.7 parts of povidone, 1.4-2.1 parts of sodium carboxymethylcellulose, 0.08-0.11 part of chitosan, 0.19-0.23 part of monocalcium phosphate, 35-40 parts of hypromellose, 9-11 parts of microcrystalline cellulose and 0.5-1.5 parts of magnesium stearate;
wherein the mass ratio of the povidone to the sodium carboxymethyl cellulose is 3: 1.2-2; the mass ratio of the chitosan to the monocalcium phosphate is 1: 2-3.
3. The preparation method of the metformin hydrochloride sustained release tablet according to any one of claims 1 to 2, wherein the absorption enhancer, the metformin hydrochloride and the binder are mixed and granulated, then mixed with the hypromellose and the pharmaceutical excipients, and tableted to obtain the metformin hydrochloride sustained release tablet.
4. The method for preparing the metformin hydrochloride sustained release tablet according to claim 3, wherein the mixing granulation comprises: preparing solution A by using the absorption enhancer, uniformly mixing the metformin hydrochloride and the binding agent, then mixing with the solution A, carrying out wet granulation, drying and finishing granules.
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| CN1415288A (en) * | 2002-10-22 | 2003-05-07 | 南京长澳医药科技有限公司 | Metformin hydrochloride slowly released tablet and its preparation method |
| CN102119931A (en) * | 2011-02-21 | 2011-07-13 | 寿光富康制药有限公司 | Novel metformin hydrochloride slow-releasing tablet and preparation method thereof |
| CN104072513A (en) * | 2014-06-16 | 2014-10-01 | 南京泽朗医药科技有限公司 | Preparation method of Ovatodiolide and application of Ovatodiolide in anti-tumor drugs |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1415288A (en) * | 2002-10-22 | 2003-05-07 | 南京长澳医药科技有限公司 | Metformin hydrochloride slowly released tablet and its preparation method |
| CN102119931A (en) * | 2011-02-21 | 2011-07-13 | 寿光富康制药有限公司 | Novel metformin hydrochloride slow-releasing tablet and preparation method thereof |
| CN104072513A (en) * | 2014-06-16 | 2014-10-01 | 南京泽朗医药科技有限公司 | Preparation method of Ovatodiolide and application of Ovatodiolide in anti-tumor drugs |
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Denomination of invention: Metformin hydrochloride sustained release tablets and preparation method thereof Effective date of registration: 20220124 Granted publication date: 20200313 Pledgee: Chongqing Rural Commercial Bank Co.,Ltd. Qianjiang sub branch Pledgor: CHONGQING KERUI NANHAI PHARMACEUTICAL Co.,Ltd. Registration number: Y2022500000003 |
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