Metformin hydrochloride tablet and preparation method thereof
By selecting appropriate auxiliary materials and controlling the preparation process in the preparation of metformin hydrochloride tablets, the problem of low dissolution of metformin hydrochloride tablets is solved, the drug absorption speed and bioavailability are improved, and the efficacy and safety are ensured.
Patent Information
- Application Number
- CN202411106501.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-13
- Publication Date
- 2024-12-17
AI Technical Summary
The dissolution of existing metformin hydrochloride tablets is low, resulting in slow drug release, affecting the absorption rate and bioavailability. The blood drug concentration varies greatly after taking the same dose in different individuals, affecting the efficacy and safety.
By selecting high-quality metformin hydrochloride raw materials and fillers with particle size matching fillers and disintegrants, wet granulation and tableting technology are used to control the tableting pressure, and microcrystalline cellulose, sodium carboxymethyl starch and 100% Sodium dialkyl sulfate is used as an auxiliary material to improve the dispersion and dissolution rate of the drug.
It significantly improves the dissolution of metformin hydrochloride tablets, ensures the uniform absorption of the drug in the body and stabilizes the blood drug concentration, and improves the efficacy and safety.
Smart Images
Figure CN119139253A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of metformin hydrochloride tablet preparation, in particular to a metformin hydrochloride tablet and a preparation method thereof. Background Art
[0002] Metformin hydrochloride tablets are used for patients with type II diabetes who are not satisfied with diet control alone, especially those who are obese and have hyperinsulinemia. This drug not only has the effect of lowering blood sugar, but also may reduce weight and hyperinsulinemia. It can be effective for patients with poor efficacy of certain sulfonylureas. For example, when used in combination with sulfonylureas, α-glucosidase inhibitors or thiazolidinediones hypoglycemic drugs, the effect is better than using them alone. It can also be used for patients treated with insulin to reduce the amount of insulin.
[0003] The existing metformin hydrochloride tablets have the problem of low solubility. The low solubility will lead to a slower release of the drug from the tablet into the dissolution medium, affecting the absorption rate and extent of the drug in the body, resulting in reduced bioavailability. The efficacy of the drug may not be fully exerted, and the inconsistency of dissolution may lead to increased differences in blood drug concentrations after different individuals take the same dose of the drug, affecting the efficacy and safety of the drug. For this reason, we propose a metformin hydrochloride tablet and a preparation method thereof. Summary of the invention
[0004] The object of the present invention is to provide a metformin hydrochloride tablet and a preparation method thereof, so as to solve the problems raised in the above-mentioned background technology.
[0005] To achieve the above object, the present invention provides the following technical solution: a method for preparing metformin hydrochloride tablets, the method for preparing metformin hydrochloride tablets comprising the following specific steps:
[0006] S1. Prepare raw materials, select high-quality metformin hydrochloride raw materials, and screen the raw materials to ensure that the purity and particle size of the metformin hydrochloride raw materials meet the requirements. Smaller particle size can increase the contact area between the drug and the dissolution medium, which is beneficial to improve the dissolution rate;
[0007] S2. Selection of excipients: selecting fillers, disintegrants and cosolvents as excipients, and sieving the fillers and disintegrants to ensure that the particle sizes of the fillers and disintegrants match those of the metformin hydrochloride raw materials, thereby effectively improving the dissolution rate;
[0008] S3, preparing, fully mixing the metformin hydrochloride raw material with the filler in the auxiliary material to improve the uniformity and dissolution of the tablets;
[0009] S4, granulation, wet granulation of the mixed materials to make a suitable soft material, and then pass through a sieve to make wet granules. Wet granulation can make the drug better dispersed in the excipients. The wet granules are dried, and then the whole granules after drying are mixed with a disintegrant and a cosolvent;
[0010] S5. Tableting: Use a tablet press to press the mixed granules into tablets. The tableting pressure needs to be controlled during this process. Appropriate tableting pressure can ensure the hardness and disintegration performance of the tablets, thereby affecting the dissolution rate. Too high a pressure may cause the tablets to be too dense and the dissolution rate to decrease. Too low a pressure may cause the tablets to be loose, affecting the quality.
[0011] S6. Quality inspection: conduct quality inspection on compressed tablets to ensure that the products meet relevant quality standards.
[0012] Preferably, the metformin hydrochloride raw material, filler and disintegrant are sieved through a mesh size of 60-200 mesh.
[0013] Preferably, the filler is microcrystalline cellulose, which can improve the tablet's formability and dissolution properties; the disintegrant is sodium carboxymethyl starch, which helps the tablet to disintegrate rapidly in the dissolution medium and increases the drug's dissolution rate; the cosolvent is sodium dodecyl sulfate, which can increase the drug's wettability and solubility and further improve the solubility.
[0014] Preferably, in S3, the metformin hydrochloride raw material and the filler are placed in a three-dimensional mixer for thorough mixing to ensure that the drug is evenly distributed in the excipients, and the mixing time is 15-30 minutes.
[0015] Preferably, the granulation in S4 comprises the following specific steps:
[0016] S4.1. Add appropriate amount of adhesive to the mixed materials to make suitable soft materials, and then pass through a sieve to make wet granules;
[0017] S4.2, placing the obtained wet granules into a drying device for drying, removing the water, and controlling the water content of the granules;
[0018] S4.3. After drying, there may be some large particles or agglomerates in the granules. The dried granules are put into a granulator for granulation to obtain granules with uniform particle size.
[0019] S4.4. Place the sorted granules, disintegrant and co-solvent into a three-dimensional mixer and mix thoroughly for 30-50 minutes to ensure uniform distribution in the granules.
[0020] Preferably, the adhesive in S4.1 is a povidone K30 solution.
[0021] Preferably, the drying temperature of the drying equipment in S4.2 is controlled at 50-60° C., and the drying time is 2-3 hours.
[0022] Preferably, the quality inspection of the compressed tablets in S6 includes inspection of appearance, tablet weight difference, hardness, friability, and dissolution index.
[0023] Preferably, in the preparation process of S3, when the metformin hydrochloride raw material is mixed with the filler in the auxiliary material, the metformin hydrochloride raw material and the filler are divided into three parts, the first part of the metformin hydrochloride raw material and the filler are put into a three-dimensional mixer for mixing, the mixing time is 10 minutes, after the mixing is completed, the three-dimensional mixer is opened, the mixing state of the metformin hydrochloride raw material and the filler in the mixer is observed, the second part of the metformin hydrochloride raw material and the filler are put into the mixer, and the mixture is mixed again, the mixing time is 10 minutes, after the second mixing is completed, the three-dimensional mixer is opened, and the mixture is taken. A small amount of sample is taken out for testing of mixing uniformity, wherein the testing method is to evaluate the mixing effect through chemical analysis. If the mixing is uneven, it needs to be remixed. If the mixing meets the standard, the third portion of metformin hydrochloride raw material and filler are added for mixing. The mixing time is 10 minutes. After the third mixing, a small amount of sample is taken out again for testing. If the test is qualified, the next step is entered. If it is unqualified, mixing is performed again. By adding in batches, the mixing effect can be improved, and the dispersibility of the drug in the excipients can be improved, thereby further improving the solubility.
[0024] A metformin hydrochloride tablet is prepared from a metformin hydrochloride raw material and auxiliary materials, and the metformin hydrochloride tablet is prepared by the preparation method according to claims 1 to 9.
[0025] Compared with the prior art, the present invention provides a metformin hydrochloride tablet and a preparation method thereof, which have the following beneficial effects:
[0026] 1. The metformin hydrochloride tablets and the preparation method thereof effectively improve the mixing effect by mixing the metformin hydrochloride raw material and the auxiliary materials in three steps and evaluating the results of the second and third mixing, thereby improving the dispersibility of the drug in the auxiliary materials and improving the dissolution rate.
[0027] 2. The metformin hydrochloride tablets and the preparation method thereof screen the metformin hydrochloride raw materials and auxiliary materials to ensure that the particle sizes of the metformin hydrochloride raw materials and auxiliary materials are close, so that the metformin hydrochloride raw materials and auxiliary materials can be more uniform when mixed, thereby helping to improve the dissolution rate.
[0028] 3. The metformin hydrochloride tablets and the preparation method thereof use microcrystalline cellulose as a filler, sodium carboxymethyl starch as a disintegrant and sodium lauryl sulfate as a cosolvent to improve the tablet's formability and dissolution performance and increase the dissolution rate. BRIEF DESCRIPTION OF THE DRAWINGS
[0029] Figure 1 It is a schematic diagram of the specific preparation steps of the present invention;
[0030] Figure 2 It is a schematic diagram of the preparation steps of the present invention;
[0031] Figure 3 It is a schematic diagram of the auxiliary material of the present invention. DETAILED DESCRIPTION
[0032] like Figure 1-Figure 3 As shown, the present invention provides a technical solution: a method for preparing metformin hydrochloride tablets, the method for preparing metformin hydrochloride tablets comprising the following specific steps:
[0033] S1. Prepare raw materials, select high-quality metformin hydrochloride raw materials, and screen the raw materials to ensure that the purity and particle size of the metformin hydrochloride raw materials meet the requirements. Smaller particle size can increase the contact area between the drug and the dissolution medium, which is beneficial to improve the dissolution rate;
[0034] S2. Selection of excipients: selecting fillers, disintegrants and cosolvents as excipients, and sieving the fillers and disintegrants to ensure that the particle sizes of the fillers and disintegrants match those of the metformin hydrochloride raw materials, thereby effectively improving the dissolution rate;
[0035] S3, preparing, putting metformin hydrochloride raw material and filler into a three-dimensional mixer and mixing them fully to improve the uniformity and dissolution of the tablets to ensure that the drug is evenly distributed in the excipients, and the mixing time is 15-30min;
[0036] S4, granulation, wet granulation of the mixed materials, wet granulation can make the drug better dispersed in the excipients, add an appropriate amount of adhesive to the mixed materials, the adhesive uses povidone K30 solution, make a suitable soft material, and then pass through a sieve to make wet granules, put the obtained wet granules into a drying equipment for drying, remove the water, and control the moisture content of the granules. The drying temperature of the drying equipment is controlled at 50-60°C, and the drying time is 2-3h. There may be some larger particles or lumps in the dried granules. The dried granules are put into a granulator for granulation to obtain granules with uniform particle size, and the granules after granulation are put into a three-dimensional mixer with a disintegrant and a cosolvent for sufficient mixing. The mixing time is 30-50min to ensure uniform distribution in the granules;
[0037] S5. Tableting: Use a tablet press to press the mixed granules into tablets. The tableting pressure needs to be controlled during this process. Appropriate tableting pressure can ensure the hardness and disintegration performance of the tablets, thereby affecting the dissolution rate. Too high a pressure may cause the tablets to be too dense and the dissolution rate to decrease. Too low a pressure may cause the tablets to be loose, affecting the quality.
[0038] S6. Quality inspection: quality inspection is carried out on the compressed tablets, including inspection of appearance, tablet weight difference, hardness, friability, and dissolution index to ensure that the product meets the relevant quality standards.
[0039] The metformin hydrochloride raw material, filler and disintegrant are sieved with a mesh number of 60-200 meshes. Microcrystalline cellulose is selected as the filler, which can improve the formability and dissolution performance of the tablet. The disintegrant is sodium carboxymethyl starch, which helps the tablet to disintegrate rapidly in the dissolution medium and improves the dissolution rate of the drug. The co-solvent is sodium dodecyl sulfate, which can increase the wettability and solubility of the drug and further improve the solubility.
[0040] During the preparation process of S3, when the metformin hydrochloride raw material and the filler in the auxiliary material are mixed, the metformin hydrochloride raw material and the filler are divided into three parts, and the first part of the metformin hydrochloride raw material and the filler are put into a three-dimensional mixer for mixing, and the mixing time is 10 minutes. After the mixing is completed, the three-dimensional mixer is opened, and the mixing state of the metformin hydrochloride raw material and the filler in the mixer is observed, and the second part of the metformin hydrochloride raw material and the filler are put into the mixer, and the mixing is carried out again for 10 minutes. After the second mixing is completed, the three-dimensional mixer is opened, and a small amount of sample is taken out for mixing uniformity detection, wherein the detection method evaluates the mixing effect in the form of chemical analysis. If the mixing is uneven, it needs to be remixed again. If the mixing meets the standard, the third part of the metformin hydrochloride raw material and the filler are put into the mixer for mixing, and the mixing time is 10 minutes. After the third mixing is completed, a small amount of sample is taken out again for detection. If the detection is qualified, the next step is entered. If it is unqualified, it is mixed again. By adding in batches, the mixing effect can be improved, and the dispersibility of the drug in the auxiliary material can be improved, and the solubility can be further improved.
[0041] A metformin hydrochloride tablet is prepared from a metformin hydrochloride raw material and auxiliary materials. The metformin hydrochloride tablet is prepared by the preparation method of claims 1 to 9.
[0042] The above generally describes the present invention in detail, but it is obvious to a person skilled in the art that some modifications or improvements can be made to the present invention. Therefore, modifications or improvements that do not depart from the spirit of the present invention are within the scope of protection of the present invention.
Claims
1. A method for preparing metformin hydrochloride tablets, characterized in that: The preparation method of the metformin hydrochloride tablets comprises the following specific steps: S1. Prepare raw materials, select high-quality metformin hydrochloride raw materials, and screen the raw materials to ensure that the purity and particle size of the metformin hydrochloride raw materials meet the requirements. Smaller particle size can increase the contact area between the drug and the dissolution medium; S2. Selection of excipients: selecting fillers, disintegrants and cosolvents as excipients, and sieving the fillers and disintegrants to ensure that the particle sizes of the fillers and disintegrants match those of the metformin hydrochloride raw material; S3, preparing by fully mixing the metformin hydrochloride raw material with the filler in the auxiliary material; S4, granulation, wet granulation of the mixed material to make a suitable soft material, then pass through a sieve to make wet granules, dry the wet granules, and then mix the whole granules after drying with a disintegrant and a solubility aid; S5. Tableting: Use a tablet press to press the mixed granules into tablets. The tableting pressure needs to be controlled during this process. Appropriate tableting pressure can ensure the hardness and disintegration performance of the tablets, thereby affecting the dissolution rate. Too high a pressure may cause the tablets to be too dense and the dissolution rate to decrease. Too low a pressure may cause the tablets to be loose, affecting the quality. S6. Quality inspection: conduct quality inspection on compressed tablets to ensure that the products meet relevant quality standards.
2. The method for preparing metformin hydrochloride tablets according to claim 1, characterized in that: The metformin hydrochloride raw material, filler and disintegrant are sieved through a mesh number of 60-200 meshes.
3. The method for preparing metformin hydrochloride tablets according to claim 1, characterized in that: The filler is microcrystalline cellulose, the disintegrant is sodium carboxymethyl starch, and the cosolvent is sodium lauryl sulfate.
4. The method for preparing metformin hydrochloride tablets according to claim 1, characterized in that: In S3, the metformin hydrochloride raw material and the filler are placed in a three-dimensional mixer and fully mixed for a mixing time of 15-30 minutes.
5. The method for preparing metformin hydrochloride tablets according to claim 1, characterized in that: The granulation in S4 comprises the following specific steps: S4.
1. Add appropriate amount of adhesive to the mixed materials to make suitable soft materials, and then pass through a sieve to make wet granules; S4.2, placing the obtained wet granules into a drying device for drying, removing the water, and controlling the water content of the granules; S4.
3. After drying, there may be some large particles or agglomerates in the granules. The dried granules are put into a granulator for granulation to obtain granules with uniform particle size. S4.
4. Place the sorted granules, disintegrant and co-solvent into a three-dimensional mixer and mix thoroughly for 30-50 minutes to ensure uniform distribution in the granules.
6. The method for preparing metformin hydrochloride tablets according to claim 5, characterized in that: The adhesive in S4.1 is a povidone K30 solution.
7. The method for preparing metformin hydrochloride tablets according to claim 5, characterized in that: The drying temperature of the drying equipment in S4.2 is controlled at 50-60° C., and the drying time is 2-3 hours.
8. The method for preparing metformin hydrochloride tablets according to claim 1, characterized in that: The quality inspection of the compressed tablets in S6 includes inspection of appearance, tablet weight difference, hardness, friability, and dissolution index.
9. The method for preparing metformin hydrochloride tablets according to claim 1, characterized in that: During the preparation process of S3, when the metformin hydrochloride raw material and the filler in the auxiliary material are mixed, the metformin hydrochloride raw material and the filler are divided into three parts, the first part of the metformin hydrochloride raw material and the filler are put into a three-dimensional mixer for mixing, and the mixing time is 10 minutes. After the mixing is completed, the three-dimensional mixer is opened, and the mixing state of the metformin hydrochloride raw material and the filler in the mixer is observed. The second part of the metformin hydrochloride raw material and the filler are put into the mixer, and the mixing is carried out again for 10 minutes. After the second mixing is completed, the three-dimensional mixer is opened, and a small amount of sample is taken out for mixing uniformity detection, wherein the detection method evaluates the mixing effect in the form of chemical analysis. If the mixing is uneven, it needs to be remixed again. If the mixing meets the standard, the third part of the metformin hydrochloride raw material and the filler are put into the mixer for mixing, and the mixing time is 10 minutes. After the third mixing is completed, a small amount of sample is taken out again for detection. If the detection is qualified, the next step is entered. If it is unqualified, it is mixed again.
10. A metformin hydrochloride tablet, characterized in that: The metformin hydrochloride tablets are prepared from metformin hydrochloride raw materials and auxiliary materials, and the metformin hydrochloride tablets are prepared by the preparation methods described in claims 1 to 9.