Preparation method of pioglitazone metformin tablet
By accurately weighing and controlling the preparation steps, the material is ensured to be evenly dispersed and isolated from external factors, thus solving the problem of impurities in the production of pioglitazone metformin tablets and improving the quality and stability of the drug.
Patent Information
- Application Number
- CN202511175886.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-21
- Publication Date
- 2025-11-07
AI Technical Summary
Existing technologies are prone to generating impurities during the preparation of pioglitazone metformin tablets, resulting in poor drug quality.
By employing precise weighing of each material component, pretreatment of active pharmaceutical ingredient, premixing, wet granulation, wet sizing, drying, dry sizing, total mixing, tableting, and coating, combined with specific frequency and temperature control, we ensure uniform dispersion of materials and isolation from external factors, thereby reducing the generation of impurities.
The prepared pioglitazone metformin tablets have good quality, fewer impurities, and high content stability, thus solving the problem of impurity generation.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to a preparation method of a medicine, in particular a preparation method of pioglitazone metformin tablets, and belongs to the field of pharmacy. BACKGROUND
[0002] Pioglitazone metformin tablets are oral anti-hyperglycemic pioglitazone and metformin hydrochloride compound preparations, metformin hydrochloride can reduce the production of liver glycogen, reduce the absorption of sugar in the intestine, and can improve the sensitivity of insulin by increasing the uptake and utilization of peripheral sugar; pioglitazone is a thiazolidinedione hypoglycemic drug, which mainly increases the sensitivity of tissues to insulin to produce a hypoglycemic effect, and is used for the treatment of type 2 diabetes. It is suitable for the treatment of type 2 diabetes patients currently treated with pioglitazone hydrochloride and metformin hydrochloride combination therapy or type 2 diabetes patients with poor blood glucose control after treatment with metformin hydrochloride alone on the basis of diet control and exercise.
[0003] At present, in the preparation of pioglitazone metformin tablets, related impurities are produced, and the problem of impurity interference occurs, resulting in poor quality of the medicine obtained by production and preparation, and the quality of the medicine needs to be improved. SUMMARY
[0004] The technical problem to be solved by the present application is to provide a preparation method of pioglitazone metformin tablets, which solves the problem of easy impurity generation in the production process of the preparation of pioglitazone metformin tablets in the prior art.
[0005] To solve the above technical problems, the technical scheme adopted by the present application is: A preparation method of pioglitazone metformin tablets, the components of the pioglitazone metformin tablets include raw materials: pioglitazone hydrochloride, metformin hydrochloride, and excipients: microcrystalline cellulose, povidone K30, cross-linked sodium carboxymethyl cellulose, magnesium stearate, and a gastric soluble film coating premix; The preparation method comprises the following steps: S1, weighing: respectively weighing the prescription amount of pioglitazone hydrochloride and metformin hydrochloride raw materials; and respectively weighing the prescription amount of microcrystalline cellulose, povidone K30, cross-linked sodium carboxymethyl cellulose, magnesium stearate, and a gastric soluble film coating premix for standby; S2, raw material pretreatment: sieving the metformin hydrochloride, screen mesh aperture: 1.2mm screen; whole grain machine speed: 300-1200rpm; standby; S3, premixing: dividing the pretreated metformin hydrochloride into two batches, and sequentially adding the first batch of metformin hydrochloride, pioglitazone hydrochloride, povidone K30, microcrystalline cellulose, and the second batch of metformin hydrochloride into the wet mixing granulator for operation; S4, wet granulation: purified water is weighed and added to the concentrated tank for standby; the wet mixing granulator is started, and purified water is added in the form of atomization to granulate, with the liquid addition time controlled at 2-3 min; after the liquid addition is completed, granulation is continued for 30 s; S5, wet granulation: a square screen with a pore size of 6x6 mm is selected, the speed of the wet granulator is set to 600 rpm, and the wet granulation equipment is started to wet-granulate the prepared soft material; S6, granule drying: the wet-granulated material is sucked into the granule drying machine, heating is stopped when the material temperature reaches the target temperature of 27°C, sampling is performed to detect the moisture content, and drying is completed when the moisture content is 1.0%-3.0%; S7, dry granulation: the dried granules are subjected to dry granulation, a screen with a pore size of 1.2 mm is installed, and the speed of the granulator is set to 300-1200 rpm; S8, total mixing: the granules after dry granulation, auxiliary materials microcrystalline cellulose, croscarmellose sodium, and magnesium stearate are added into the mixer for mixing operation; S9, tabletting: test pressing is performed using a capsule punch, the tabletting speed is 5-20 million tablets / hour, and the uncoated tablets are obtained after tabletting is completed; S10, coating: (1) coating liquid: the coating liquid is prepared according to a solid content of 14%, purified water is accurately weighed and placed in a stirring tank, stirring is started, and the gastric-soluble film coating premix is slowly added into the purified water, stirring is performed for not less than 45 min, and the mixture is sieved through a 60-mesh screen after complete dissolution for standby; (2) coating: during the coating process, the inlet air temperature is set to 50°C, the inlet air flow is set to 4000 m³ / h, the coating speed is set to 3-10 rpm, the tablet bed temperature is controlled at 35-50°C, and the liquid spraying is stopped when the coating weight gain is 0.5%-2.0%; (3) coating drying: after the liquid spraying is completed, drying is continued for 15 min, and the pioglitazone and metformin tablets are obtained after cooling.
[0006] Further, in step S3, pre-mixing: the stirring frequency is set to 25 Hz, the cutter frequency is set to 20 Hz, and the mixing time is set to 7 min.
[0007] Further, in step S4, wet granulation: the stirring frequency is set to 25 Hz, the cutter frequency is set to 20 Hz, the atomization pressure of the concentrated tank is set to 0.22 Mpa, and the liquid addition pressure is set to 0.30 Mpa.
[0008] Further, in step S6, granule drying: the inlet air temperature is set to 40°C, and the inlet air frequency is set to 40 Hz.
[0009] Further, in step S8, total mixing: the mixing frequency is set to 30 Hz, and the mixing time is set to 5 min.
[0010] Further, in step S9, tabletting: main compression pressure 10-20KN, hardness 150-300N.
[0011] Further, in step 10, coating drying: set the air inlet temperature to 50℃, set the air inlet air volume to 4000m³ / h, and the coating rotation speed is ≤10rpm.
[0012] Further, the weight fraction of pioglitazone hydrochloride is 2.6%, the weight fraction of metformin hydrochloride is 78.4%, and the auxiliary materials: the weight fraction of microcrystalline cellulose is 8.8%, the weight fraction of povidone K30 is 5.2%, the weight fraction of croscarmellose sodium is 4.7%, the weight fraction of magnesium stearate is 0.3%, and the weight gain of the gastric soluble film coating premix is 2%.
[0013] Thanks to the above technical solutions, the present application has the following technical progress: The preparation method of the present application can prepare pioglitazone metformin tablets with good drug quality, less impurities and good content stability through accurate weighing of the weight distribution ratio of each material component, pre-treatment of the raw drug, pre-mixing, wet granulation, wet whole granulation, drying, dry whole granulation, total mixing, tabletting and coating operations. DETAILED DESCRIPTION
[0014] In order to enable personnel in the technical field to better understand the present application, the technical solutions in the embodiments of the present application will be described clearly and completely in combination with the embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.
[0015] A preparation method of pioglitazone metformin tablets, the components of the pioglitazone metformin tablets include raw drugs: the weight fraction of pioglitazone hydrochloride is 2.6%, the weight fraction of metformin hydrochloride is 78.4%, and auxiliary materials: the weight fraction of microcrystalline cellulose is 8.8%, the weight fraction of povidone K30 is 5.2%, the weight fraction of croscarmellose sodium is 4.7%, the weight fraction of magnesium stearate is 0.3%, and the weight gain of the gastric soluble film coating premix is 2%; The preparation method includes the following steps: S1, weighing: respectively weighing the prescription amount of pioglitazone hydrochloride, metformin hydrochloride raw material, and respectively weighing the prescription amount of microcrystalline cellulose, povidone K30, croscarmellose sodium, magnesium stearate and gastric soluble film coating premix, for standby use; S2, raw material pretreatment: metformin hydrochloride is sieved and granulated, screen mesh size: 1.2 mm screen; granulator speed: 300-1200 rpm; standby.
[0016] S3, premixing: the pretreated metformin hydrochloride is divided into two batches, and the first batch of metformin hydrochloride, pioglitazone hydrochloride, povidone K30, microcrystalline cellulose, and the second batch of metformin hydrochloride are sequentially added to the wet mixing granulator for operation, with a stirring frequency of 25 Hz, a cutter frequency of 20 Hz, and a mixing time of 7 min. S4, wet granulation: purified water is weighed and added to the concentration tank; the stirring frequency is set to 25 Hz, the cutter frequency is set to 20 Hz, the concentration tank is set to an atomization pressure of 0.22 Mpa, the liquid addition pressure is set to 0.30 Mpa, the wet mixing granulator is started, and the purified water is added for granulation by atomization, with a liquid addition time of 2-3 min; after the liquid addition is completed, the granulation is continued for 30 s to ensure that the material particles are uniform and have good wetting properties.
[0017] S5, wet granulation: a square screen with a pore size of 6x6 mm is selected, the granulator speed is set to 600 rpm, and the wet granulation equipment is started to perform wet granulation on the prepared soft material.
[0018] S6, drying: the wet granulated material is sucked into the granulation dryer, the inlet air temperature is set to 40℃ (40-60℃), the inlet air frequency is set to 40 Hz, the material temperature reaches the target temperature of 27℃, the heating is stopped, the sample is detected for moisture, and the drying is completed when the moisture is 1.0%-3.0%; S7, dry granulation: the dried granules are subjected to dry granulation, a screen with a pore size of 1.2 mm is installed, and the granulator speed is set to 300-1200 rpm; S8, total mixing: the dry granulated particles, additional excipients microcrystalline cellulose, croscarmellose sodium, and magnesium stearate are added to the mixer for mixing operation, with a mixing frequency of 30 Hz and a mixing time of 5 min; S9, tabletting: test pressing is performed with a capsule punch, the tabletting speed is 5-20 million tablets / hour, the main pressing pressure is 10-20 KN, the hardness is 150-300 N, the friability is not more than 1%, and there is no detection of cracking, cracking, and crushing pieces; after tabletting is completed, the tablets are obtained. S10, coating: (1) The coating liquid is prepared according to a solid content of 14%. Purified water 35.26 kg is accurately weighed and placed in a stirring tank. Stirring is started. The gastric soluble film coating premix 5.74 kg is slowly added into the purified water. Stirring is not less than 45 min. After complete dissolution, it is passed through a 60 mesh sieve and is ready for use. (2) Coating: During the coating process, the inlet air temperature is set to 50℃, the inlet air flow is set to 4000m³ / h, the coating speed is 3-10 rpm, the tablet bed temperature is controlled to 35-50℃, and when the coating weight gain is 0.5%-2.0%, the liquid spraying is stopped. (3) Drying: After the liquid spraying is finished, the inlet air temperature is set to 50℃, the inlet air flow is set to 4000m³ / h, the coating speed is ≤10 rpm, and the drying is continued for 15 min. After the drying is finished, the temperature is lowered, and the pioglitazone metformin tablets are obtained.
[0019] Example 1 A preparation method of pioglitazone metformin tablets. The components of the pioglitazone metformin tablets include raw materials: the weight part of pioglitazone hydrochloride is 2.6%, the weight part of metformin hydrochloride is 78.4%, and excipients: the weight part of microcrystalline cellulose is 8.8%, the weight part of povidone K30 is 5.2%, the weight part of croscarmellose sodium is 4.7%, the weight part of magnesium stearate is 0.3%, and the weight gain of gastric soluble film coating premix is 2%. The amount is shown in Table 1 below: Table 1: Raw material amount table of Example 1
[0020] The preparation method includes the following steps: S1, weighing: the prescription amount of pioglitazone hydrochloride and metformin hydrochloride raw materials is weighed respectively and is ready for use. The prescription amount of microcrystalline cellulose, povidone K30, croscarmellose sodium, magnesium stearate, and gastric soluble film coating premix is weighed respectively and is ready for use. S2, raw material pretreatment: the metformin hydrochloride is sieved and is ready for use. The sieve mesh size is 1.2 mm. The speed of the granulator is 300-1200 rpm.
[0021] S3, premixing: the pretreated metformin hydrochloride is divided into two batches. The first batch of metformin hydrochloride, pioglitazone hydrochloride, povidone K30, microcrystalline cellulose, and the second batch of metformin hydrochloride are sequentially added into the wet granulator. The stirring frequency is set to 25 Hz, the cutter frequency is set to 20 Hz, and the mixing time is 7 min. S4, wet granulation: purified water is weighed and added to the concentration tank, standby; set the stirring frequency to 25 Hz, the cutter frequency to 20 Hz, the concentration tank to the atomization pressure of 0.22 Mpa, the liquid pressure to 0.30 Mpa, start the wet mixing granulator, add purified water by atomization to granulate, control the liquid adding time to 2-3 min, continue granulating for 30 s after the liquid adding is completed, to ensure that the material particles are uniform and have good wetting properties.
[0022] S5, wet granulation: select a square screen with a pore size of 6x6 mm, set the speed of the wet granulator to 600 rpm, start the wet granulation equipment, and wet granulate the prepared soft material.
[0023] S6, drying: the wet granulated material is sucked into the granulator dryer, the inlet air temperature is set to 40℃ (40-60℃), the inlet air frequency is set to 40 Hz, the material temperature reaches the target temperature of 27℃, the heating is stopped, the moisture is detected by sampling, and the drying is completed when the moisture is 1.0%-3.0%; S7, dry granulation: the dried granules are subjected to dry granulation, the screen aperture is 1.2 mm, and the granulator speed is set to 300-1200 rpm; S8, total mixing: the granules after dry granulation, plus auxiliary materials microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose and magnesium stearate are put into the mixer for mixing operation, the mixing frequency is set to 30 Hz, and the mixing time is 5 min; S9, tabletting: test pressure with a capsule punch, tabletting speed 5-20 million tablets / hour, main pressure 10-20 KN, hardness 150-300 N, friability not more than 1%, and no broken, cracked and crushed pieces are detected, and the tablet is obtained after tabletting; S10, coating: (1) coating liquid is prepared according to the solid content of 14%, purified water 35.26 kg is accurately weighed and placed in the stirring tank, stirring is started, and gastric soluble film coating premix 5.74 kg is slowly added into the purified water, stirring is not less than 45 min, and after complete dispersion, it is passed through a 60 mesh screen, standby; (2) coating: during the coating process, the inlet air temperature is set to 50℃, the inlet air volume is set to 4000 m³ / h, the coating speed is 3-10 rpm, the tablet bed temperature is controlled to 35-50℃, and when the coating weight gain is 0.5%-2.0%, the liquid spraying is stopped; (3) drying: after the liquid spraying is completed, the inlet air temperature is set to 50℃, the inlet air volume is set to 4000 m³ / h, the coating speed is ≤10 rpm, and the drying is continued for 15 min, the drying is completed, the temperature is lowered, and the pioglitazone metformin tablets are obtained.
[0024] Example 2 A preparation method of pioglitazone metformin tablets, the components of the pioglitazone metformin tablets include raw materials: 2.6% by weight of pioglitazone hydrochloride, 78.4% by weight of metformin hydrochloride, and auxiliary materials: 8.8% by weight of microcrystalline cellulose, 5.2% by weight of povidone K30, 4.7% by weight of cross-linked sodium carboxymethyl cellulose, 0.3% by weight of magnesium stearate, and 2% of weight gain of gastric soluble film coating premix; the amounts are shown in Table 2 as follows: Table 2: Amounts of raw and auxiliary materials of Example 2
[0025] The operation steps of the preparation method are the same as those of Example 1.
[0026] Example 3 A preparation method of pioglitazone metformin tablets, the components of the pioglitazone metformin tablets include raw materials: 2.6% by weight of pioglitazone hydrochloride, 78.4% by weight of metformin hydrochloride, and auxiliary materials: 8.8% by weight of microcrystalline cellulose, 5.2% by weight of povidone K30, 4.7% by weight of cross-linked sodium carboxymethyl cellulose, 0.3% by weight of magnesium stearate, and 2% of weight gain of gastric soluble film coating premix; the amounts are shown in Table 3 as follows: Table 3: Amounts of raw and auxiliary materials of Example 3
[0027] The operation steps of the preparation method are the same as those of Example 1.
[0028] The pioglitazone metformin tablets obtained in Examples 1, 2, and 3 are respectively subjected to related substance detection and content detection, and the results are shown in the following table: Table 4: Quality detection data
[0029] Conclusion: The related substance of metformin hydrochloride is ≤0.5% in total impurities, the related substance of pioglitazone is ≤0.6% in total impurities, the content of pioglitazone hydrochloride should be 95.0%-105.0% of the labeled amount of pioglitazone, and the content of metformin hydrochloride should be 95.0%-105.0% of the labeled amount. According to the above standards, the total impurities of the related substance of metformin hydrochloride, the total impurities of the related substance of pioglitazone, the content of pioglitazone hydrochloride, and the content of metformin hydrochloride in the pioglitazone metformin tablets obtained in Examples 1, 2, and 3 all meet the requirements, and the quality of the drug is good.
[0030] The pioglitazone metformin tablets prepared in Example 1, 2, and 3 were subjected to 6-month accelerated stability test at 40℃±2℃ and 75%±5% relative humidity, and the total impurities of related substances, content were detected, and the changes were observed. The reference standards were as follows: the total impurities of related substances of metformin hydrochloride should be ≤0.5%, the total impurities of related substances of pioglitazone should be ≤0.6%, the content of pioglitazone hydrochloride calculated as pioglitazone should be 95.0%-105.0% of the labeled amount, and the content of metformin hydrochloride should be 95.0%-105.0% of the labeled amount. The specific results are shown in the following table. Table 5: Stability test
[0031] Conclusion: The pioglitazone metformin tablets prepared in Example 1, 2, and 3 were subjected to quality stability test. According to the test results, the total impurities of related substances of metformin hydrochloride in Example 1, 2, and 3 were not detected during the stability test, indicating that the production process was well controlled, and the pioglitazone metformin tablets prepared did not produce metformin hydrochloride related substances, and would not produce metformin hydrochloride related substances during storage. The impurities were effectively controlled. During the stability test, the total impurities of related substances of pioglitazone showed a slight upward trend, but the overall change was stable, and the total impurities were low. The content (containing pioglitazone hydrochloride) and content (containing metformin hydrochloride) showed a slight downward trend during the stability test, but the overall change was stable, and the change was not large, and all remained within the qualified range, and the content was stable.
[0032] Comparative Example 1 As a comparative experiment of Example 1, the influence of the mixing process and dispersion degree of each substance during the preparation process on the quality of the drug was investigated. The prescription amount of the substance composition and ratio of Comparative Example 1 were the same as those of Example 1. The mixing and dispersion in the preparation process of Comparative Example 1 were as follows: Pre-mixing: The pretreated metformin hydrochloride was directly put into the mixing as a batch, and metformin hydrochloride, pioglitazone hydrochloride, povidone K30, and microcrystalline cellulose were sequentially added into the wet granulation machine for operation. The stirring frequency was set to 25 Hz, the cutter frequency was set to 20 Hz, and the mixing time was set to 7 min.
[0033] The remaining operation steps were the same as those of Example 1.
[0034] The difference between Comparative Example 1 and Example 1 is in the mixing method. In the mixing process, Comparative Example 1 directly feeds metformin hydrochloride as a batch, while Example 1 divides metformin hydrochloride into two batches and feeds them in sequence. Under the same mixing conditions (same mixing frequency and same mixing time), Comparative Example 1 has the problem of insufficient mixing and uneven dispersion because a large amount of metformin hydrochloride is concentrated in one area after feeding. Example 1 has sufficient mixing and uniform dispersion because a large amount of metformin hydrochloride is divided into two batches and fed in sequence, thereby avoiding the reaction of the active ingredients of the raw materials and the generation of impurities. In addition, the mixing method of Example 1 achieves the purpose of sufficient mixing and uniform dispersion in a short time, thereby improving the production efficiency.
[0035] Comparative Example 2 As a comparative experiment of Example 1, the influence of different material composition on the quality of the drug was mainly investigated. The material composition in the prescription process of Comparative Example 2 is shown in the following table: Table 6: Dosage table of raw and auxiliary materials of Comparative Example 2
[0036] In which, the microcrystalline cellulose in the auxiliary materials of Example 1 is replaced by pregelatinized starch, the weight ratio is unchanged, and the addition method is unchanged (including internal and external addition). The operation steps of the preparation method are the same as those of Example 1.
[0037] The difference between Comparative Example 2 and Example 1 is that the composition of the auxiliary materials is different. The difference between microcrystalline cellulose and pregelatinized starch affects the quality of the drug. In the preparation process, the change of the composition of the auxiliary materials may cause the degradation of the active ingredients of the raw materials and the generation of impurities.
[0038] Comparative Example 3 As a comparative experiment of Example 1, the influence of the ratio of each material composition in the prescription process on the quality of the drug was mainly investigated. The ratio of the material composition in the prescription process of Comparative Example 3 is shown in the following table: Table 7: Dosage table of raw and auxiliary materials of Comparative Example 3
[0039] The operation steps of the preparation method are the same as those of Example 1.
[0040] The difference between Comparative Example 3 and Example 1 is that the ratio of the components of the materials is different. The ratio of the components of the materials affects the mixing and dispersion of the materials, the uniformity of the mixing and dispersion of the materials, and the content of the materials, which can cause the degradation of the content and the generation of impurities.
[0041] Comparative Example 4 As a comparative experiment of Example 1, the influence of coating operation on the quality of the drug was mainly investigated. The prescription process of Comparative Example 4 does not contain the gastric soluble film coating premix, and the other materials are the same as Example 1, as shown in the following table: Table 8: Material usage of Comparative Example 4
[0042] The preparation method does not have a coating operation, and the other operation steps are the same as Example 1.
[0043] The difference between Comparative Example 4 and Example 1 is that the tablets are not coated in Comparative Example 4, while the drug is coated in Example 1. The coating operation protects the tablets and isolates the influence of external factors on the tablets, avoiding the introduction of external impurities, thereby reducing the generation of impurities.
[0044] The pioglitazone metformin tablets prepared in Comparative Examples 1, 2, 3, and 4 were subjected to related substance and content detection, and the results are shown in the following table: Table 9: Quality detection data of comparative experiments
[0045] Conclusion: After quality detection of Comparative Examples 1, 2, 3, and 4, compared with the quality detection results of Example 1, the impurities increased significantly. Example 1 uses a preparation method that controls the composition of the materials and the ratio of the components during the mixing and dispersion of the materials, and controls the parameters at each stage during the preparation operation. Finally, through the coating operation and the control of the coating parameters, a drug with stable content and low impurities is obtained, which ensures the quality of the drug.
[0046] The preparation method of the present application is prepared by accurate weighing of the weight distribution ratio of each material component, pre-treatment of the raw material, pre-mixing, wet granulation, wet granulation, drying, dry granulation, total mixing, tabletting, coating operation steps, and the prepared pioglitazone metformin tablets have good drug quality, less impurities and good content stability. Specifically, the preparation method of the present application first mixes and uniformly disperses the raw materials of pioglitazone metformin tablets to avoid the reaction of active ingredients that may occur due to the aggregation of active ingredients, thereby generating impurities; secondly, by designing the material composition and the ratio of each component in the prescription process, the degradation of active ingredients of the raw materials and the generation of impurities are avoided during the mixing and dispersion process of the auxiliary materials and the raw materials; the reaction between the auxiliary materials and the raw materials is also avoided, thereby reducing the generation of impurities; finally, isolation control is performed in the steps of the preparation method, wherein the coating operation protects the tablets and isolates the influence of external factors on the tablets, thereby avoiding the introduction of external impurities and reducing the generation of impurities. Therefore, the preparation method of the present application solves the problem of easy generation of impurities in the production process of pioglitazone metformin tablets in the prior art.
[0047] The above-described embodiments are only used to illustrate the technical solutions of the present application, and not to limit them; although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that they can modify the technical solutions recorded in the foregoing embodiments, or make equivalent replacements for part of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application, and all belong to the protection scope of the present application.
Claims
1. A process for the preparation of pioglitazone metformin tablets, characterized in that, The pioglitazone metformin tablet components include raw materials: pioglitazone hydrochloride, metformin hydrochloride, and excipients: microcrystalline cellulose, povidone K30, croscarmellose sodium, magnesium stearate, and a gastric soluble film coating premix; The preparation method comprises the following steps: S1, weighing: respectively weigh the prescription amount of pioglitazone hydrochloride and metformin hydrochloride raw materials, and reserve; then respectively weigh the prescription amount of microcrystalline cellulose, povidone K30, croscarmellose sodium, magnesium stearate, and a gastric soluble film coating premix, and reserve; S2, raw material pretreatment: sieve the metformin hydrochloride, the screen mesh aperture is 1.2 mm; the granulator speed is 300-1200 rpm; and reserve; S3, premixing: divide the pretreated metformin hydrochloride into two batches, and sequentially add the first batch of metformin hydrochloride, pioglitazone hydrochloride, povidone K30, microcrystalline cellulose, and the second batch of metformin hydrochloride into a wet mixing granulator for operation; S4, wet granulation: weigh purified water and add it to a concentrated tank, and reserve; start the wet mixing granulator, and add the purified water by atomization to granulate, and control the liquid adding time to be 2-3 min; after the liquid adding is completed, continue granulating for 30 s; S5, wet granulation: select a square screen mesh with an aperture of 6*6 mm, set the granulator speed to be 600 rpm, start the wet granulation equipment, and wet granulate the prepared soft material; S6, granule drying: after the wet granulation is completed, the material is sucked into a granule drying machine, heating is stopped when the material temperature reaches the target temperature 27℃, sample detection is performed, and the drying is completed when the moisture is 1.0%-3.0%; S7, dry granulation: the dried granules are subjected to dry granulation, a screen mesh aperture of 1.2 mm is installed, and the granulator speed is set to be 300-1200 rpm; S8, total mixing: the dry granulated granules, additional excipients microcrystalline cellulose, croscarmellose sodium, and magnesium stearate are put into a mixer for mixing operation; S9, tabletting: test pressing is performed by using a capsule punch, the tabletting speed is 5-20 million tablets / hour, and the tablet is obtained after the tabletting is completed; S10, coating: (1) coating liquid: the coating liquid is prepared according to a solid content of 14%, purified water is accurately weighed and placed in a stirring tank, stirring is started, and the gastric soluble film coating premix is slowly added into the purified water, stirring is not less than 45 min, and the mixture is sieved through a 60-mesh screen after complete dispersion, and is reserved; (2) coating: during the coating process, the inlet air temperature is set to be 50℃, the inlet air flow is set to be 4000 m³ / h, the coating speed is set to be 3-10 rpm, the tablet bed temperature is controlled to be 35-50℃, and the liquid spraying is stopped when the coating weight gain is 0.5%-2.0%; (3) coating drying: after the liquid spraying is completed, the drying is continued for 15 min, the drying is completed, and the pioglitazone metformin tablet is obtained after cooling.
2. The process for preparing pioglitazone metformin tablet according to claim 1, wherein, In step S3, premixing: the stirring frequency is set to be 25 Hz, the cutter frequency is set to be 20 Hz, and the mixing time is 7 min.
3. The process for preparing pioglitazone metformin tablet according to claim 1, wherein, In step S4, wet granulation: set the stirring frequency to 25 Hz, the cutter frequency to 20 Hz, the atomization pressure of the concentrated tank to 0.22 Mpa, and the liquid pressure to 0.30 Mpa.
4. The process for preparing pioglitazone metformin tablet according to claim 1, wherein, In step S6, granule drying: set the inlet air temperature to 40℃, and the inlet air frequency to 40 Hz.
5. The process for preparing pioglitazone metformin tablet according to claim 1, wherein, In step S8, total mixing: set the mixing frequency to 30 Hz, and the mixing time to 5 min.
6. The preparation method of pioglitazone metformin tablet according to claim 1, characterized in that, In step S9, tabletting: main pressure 10-20 KN, hardness 150-300 N.
7. The process for preparing pioglitazone metformin tablet according to claim 1, wherein, In step 10, coating drying: set the inlet air temperature to 50℃, the inlet air volume to 4000 m³ / h, and the coating rotation speed to ≤10 rpm.
8. The process for preparing pioglitazone metformin tablet according to claim 1, wherein, The weight part of pioglitazone hydrochloride is 2.6%, the weight part of metformin hydrochloride is 78.4%, and the auxiliary materials: the weight part of microcrystalline cellulose is 8.8%, the weight part of povidone K30 is 5.2%, the weight part of croscarmellose sodium is 4.7%, the weight part of magnesium stearate is 0.3%, and the weight of the gastric soluble film coating premix is 2%. The weight part of pioglitazone hydrochloride is 2.6%, the weight part of metformin hydrochloride is 78.4%, and the auxiliary materials: the weight part of microcrystalline cellulose is 8.8%, the weight part of povidone K30 is 5.2%, the weight part of croscarmellose sodium is 4.7%, the weight part of magnesium stearate is 0.3%, and the weight of the gastric soluble film coating premix is 2%.