Preparation process for improving filling quality of Xinan capsule

Abstract

The invention relates to the technical field of medicine capsule production, and particularly discloses a preparation process for improving the filling quality of a Xinan capsule, which comprises the following six steps: weighing 4-5kg of hawthorn leaf extract powder and 0.5 kg of corn starch, then taking 95% ethanol, preparing a soft material, granulating, drying, crushing, adding auxiliary materials during total mixing, and filling. The auxiliary materials for improving the flowability of the medicine powder are added into the crushed medicine powder, and the auxiliary materials are mixed to cover the surface of the powder to form a hydrophobic layer and directly block water contact, so that the flowability of the medicine powder is realized, the difference between the medicine loading amount and the standard amount can be very small during filling, and the safety of the prepared capsule medicine is ensured.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical capsule manufacturing technology, specifically to a preparation process for improving the filling quality of Xin'an capsules. Background Technology

[0002] Xin'an Capsules are a traditional Chinese medicine with effects such as regulating heart rate and improving cardiovascular function, mainly used to treat mental illnesses such as anxiety and depression. The original formulation involved mixing hawthorn leaf extract powder, corn starch, and 95% ethanol to form a soft mass, granulating, drying, pulverizing, passing through a 40-mesh sieve, and then calculating the required filling amount based on the total flavonoid content in the extract powder before direct filling (the filling standard is 80mg of total flavonoids per capsule). However, in actual production, the filling amount of Xin'an Capsules sometimes exceeds or falls short of the standard amount, leading to unstable fill weight and consequently, unstable drug quality. Analysis revealed that the unstable fill weight of Xin'an Capsules was caused by the poor flowability of the capsule powder. The strong hygroscopicity of hawthorn leaf extract powder in Xin'an Capsules is the main reason for this poor flowability. Therefore, a method to improve the filling quality of Xin'an Capsules and enhance the stability of the filling quality is urgently needed. Summary of the Invention

[0003] The purpose of this invention is to provide a preparation process that improves the filling quality of Xin'an capsules, so as to solve the problem that the filling amount of existing Xin'an capsules is unstable, resulting in unstable filling quality of the drug.

[0004] To address the above issues, the following technical solution is provided: A preparation process for improving the filling quality of Xin'an capsules, characterized by comprising the following steps: S1: Soft material preparation: Weigh 4-5 kg ​​of hawthorn leaf extract powder and 0.5 kg of corn starch and pour them into a trough-type mixer. Cover the mixer and start stirring for 12-18 minutes. Then slowly add 95% ethanol into the trough-type mixer and stir for 12-18 minutes to prepare the soft material. S2: Granulation: Transfer the soft material to a gyratory pellet mill and granulate it through a 12-mesh sieve. Collect the granules on a drying tray and spread them thinly on the drying tray. S3: Drying: Place the drying trays loaded with wet materials on the drying cart in order from top to bottom. After loading, push them into the drying oven, close the oven door, open the steam valve, start the circulating fan, control the drying temperature at 75-85℃, and the drying time is 4 hours. Record the oven temperature every 2 hours. S4: Grinding: Grind the dried granules into 30-60 mesh computer-controlled powder; S5: Total Mixing: Add the pulverized medicine powder into the three-dimensional mixer, add excipients to improve the flowability of the medicine powder, close the feeding port, turn on the three-dimensional mixer and mix for 20-50 minutes, then discharge to form a filling agent; S6: Filling: Prepare 100 or more capsule shells, including the capsule body and the capsule cap. Fill all the capsule shells with the filling agent. Weigh one side of the capsule every minute during the filling process and check at any time whether the filled capsules have rubbed edges, double caps, or empty capsules.

[0005] The beneficial effects of the above technical solution are as follows: when excipients are added to the pulverized medicine powder, the excipients are mixed and cover the powder surface to form a hydrophobic layer, which directly blocks the contact of water, thereby enhancing the fluidity of the medicine powder. When filling, the difference between the medicine filling amount and the standard amount can be very small, thus ensuring the stability of the medicine filling amount and thus ensuring the quality of the medicine.

[0006] Furthermore, in step S2, the thickness of the particles spread on the baking tray does not exceed 2.5 cm.

[0007] Furthermore, the excipients used in step S5 are composed of one or more of magnesium stearate, magnesium oxide, and liquid paraffin.

[0008] Furthermore, the excipients used in step S5 account for 0.5-1.5% of the total drug amount.

[0009] Furthermore, the steps also include S7: filling difference detection. Take 10 filled capsules, accurately weigh each capsule, remove the capsule cap, pour out the contents without damaging the capsule shell, wipe the inside and outside clean with degreased cotton, and accurately weigh each capsule shell in turn, and record the weighing data.

[0010] Furthermore, the step also includes S8: disintegration time limit detection, taking 6 filled capsules, using water as a medium, and recording the time it takes for the 6 capsules to completely disintegrate. Attached Figure Description

[0011] Figure 1 This is a schematic diagram of the process flow according to an embodiment of the present invention. Detailed Implementation

[0012] The following detailed description illustrates the specific implementation method: The basic implementation examples are as follows: Figure 1 As shown: The specific implementation process is as follows: Example 1 S1: Soft material preparation: Weigh 4.13 kg of hawthorn leaf extract powder and 0.5 kg of corn starch and pour them into a trough-type mixer. Cover the mixer and start stirring for 15 minutes. Then slowly add 95% ethanol into the trough-type mixer and stir for 15 minutes to prepare the soft material. S2: Granulation: Transfer the soft material to a gyratory pellet mill and granulate it through a 12-mesh sieve. Collect the granules on a drying tray and spread them thinly on the tray with a thickness of 2.5cm. S3: Drying: Place the drying trays loaded with wet materials on the drying cart in order from top to bottom. After loading, push them into the drying oven, close the oven door, open the steam valve, start the circulating fan, control the drying temperature at 75-85℃, and the drying time is 4 hours. Record the oven temperature every 2 hours. S4: Grinding: Grind the dried granules into a 40-mesh sieve computer-controlled powder; S5: Total Mixing: Add the pulverized medicine powder into the three-dimensional mixer, and add liquid paraffin accounting for 0.5% of the total mass fraction of the medicine powder. Close the feed port, turn on the three-dimensional mixer and mix for 30 minutes to form a filling agent. S6: Filling: Prepare 100 or more gelatin hollow capsule shells purchased from Yueyang Tiantian Pharmaceutical Capsule Co., Ltd. The capsule shell includes the capsule body and the capsule cap. Fill the capsule shells with the filling agent using a strip capsule filling machine. Weigh one side of the capsule every minute during the filling process and check at any time whether the filled capsules have rubbed edges, double caps, or empty capsules. S7: Filling volume difference detection: Take 10 filled capsules, accurately weigh each capsule, remove the cap, pour out the contents without damaging the capsule shell, wipe the inside and outside clean with degreased cotton, and accurately weigh each capsule shell in turn, and record the weighing data. S8: Disintegration time test: Take 6 filled capsules, use water as a medium, and measure according to the "Standard Operating Procedure for Disintegration Time Test" to record the time it takes for the 6 capsules to completely disintegrate.

[0013] Example 2 The difference between Example 2 and Example 1 is that liquid paraffin, accounting for 1% of the total mass fraction of the powder, is added during the mixing process in step S5.

[0014] Example 3 The difference between Example 3 and Example 1 is that liquid paraffin, accounting for 1.5% of the total mass fraction of the powder, is added during the mixing process in step S5.

[0015] Comparative Example 1 The difference between Comparative Example 1 and Example 1 is that magnesium stearate, accounting for 0.5% of the total mass fraction of the powder, was added during the mixing process in step S5.

[0016] Comparative Example 2 The difference between Comparative Example 2 and Example 1 is that magnesium stearate, accounting for 1% of the total mass fraction of the powder, was added during the mixing process in step S5.

[0017] Comparative Example 3 The difference between Comparative Example 3 and Example 1 is that magnesium stearate, accounting for 1.5% of the total mass fraction of the powder, was added during the mixing process in step S5.

[0018] Comparative Example 4 The difference between Comparative Example 4 and Example 1 is that magnesium oxide, accounting for 0.5% of the total mass fraction of the powder, was added during the mixing process in step S5.

[0019] Comparative Example 5 The difference between Comparative Example 5 and Example 1 is that magnesium oxide, accounting for 1% of the total mass fraction of the powder, was added during the mixing process in step S5.

[0020] Comparative Example 6 The difference between Comparative Example 6 and Example 1 is that magnesium oxide, accounting for 1.5% of the total mass fraction of the powder, was added during the mixing process in step S5.

[0021] Comparative Example 7 The difference between Comparative Example 7 and Example 1 is that no liquid paraffin additive is added during the blending process in step S5.

[0022] Comparative Example 8 The difference between Comparative Example 8 and Comparative Example 7 is that step S6 uses gelatin hollow capsules purchased from Zhejiang Yalida Capsule Co., Ltd.

[0023] The weighing data of the 10 capsules sample in step S7 of Examples 1-3 are shown in Table 1 below: Table 1 Weighing data for Examples 1-3

[0024] The weighing data of the 10 capsules in step S7 of Comparative Examples 1-3 are shown in Table 2 below: Table 2 Weighing data for Comparative Examples 1-3

[0025] The weighing data of the 10 capsules in step S7 of Comparative Examples 4-6 are shown in Table 3 below: Table 3 Weighing data for comparative examples 4-6

[0026] The weighing data of the 10 capsules in step S7 of Comparative Examples 7-8 are shown in Table 4 below: Table 4 Weighing data for comparative examples 7-8

[0027] From the comparison of the relative standard deviation (RSD) of the fill weight differences in Tables 1-4 above, it can be seen that the RSD values ​​of the formulations after adding liquid paraffin in Examples 1-3 (1.179, 1.234, 1.168) are significantly lower than the RSD values ​​of the formulations after adding magnesium stearate in Comparative Examples 1-3 (3.880, 2.445, 2.679); they are also lower than the RSD values ​​of the formulations after adding magnesium oxide in Comparative Examples 4-6 (2.796, 2.379, 2.344); and they are also lower than the RSD values ​​of the formulations without excipients in Comparative Examples 7-8 (3.253, 3.218). In particular, the fill weight of Comparative Examples 7-8 exceeds ±5%. Therefore, it can be concluded that adding liquid paraffin to Xin'an capsules is better than adding magnesium stearate and magnesium oxide. By comparing the test data of the Xin'an capsule samples prepared by the three formulations in Examples 1-3, it can be seen from the test data that the filling effect of adding 0.5% liquid paraffin is not significantly different from that of 1.0% and 1.5%. According to the principle of adding the minimum amount of excipients, adding 0.5% liquid paraffin is the best option.

[0028] Table 5 below shows the disintegration time data of the 6 capsule samples in step S8 of Examples 1-3 and Comparative Examples 1-8: Table 5. Disintegration time data for Examples 1-3 and Comparative Examples 1-8

[0029] As can be seen from the capsule disintegration time data in Table 5 above, the disintegration time of all 11 prescription samples in Examples 1-3 and Comparative Examples 1-8 is qualified (complete disintegration within 30 minutes). Among them, the disintegration time data of Comparative Examples 7-8 shows that different gelatin empty capsule suppliers have no significant impact on the filling quality of Xin'an capsules.

[0030] The above descriptions are merely embodiments of the present invention, and common knowledge regarding specific structures and characteristics is not elaborated upon here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the structure of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A preparation process for improving the filling quality of Xin'an capsules, characterized in that, Includes the following steps: S1: Soft material preparation: Weigh 4-5 kg ​​of hawthorn leaf extract powder and 0.5 kg of corn starch and pour them into a trough-type mixer. Cover the mixer and start stirring for 12-18 minutes. Then slowly add 95% ethanol into the trough-type mixer and stir for 12-18 minutes to prepare the soft material. S2: Granulation: Transfer the soft material to a gyratory pellet mill and granulate it through a 12-mesh sieve. Collect the granules on a drying tray and spread them thinly on the drying tray. S3: Drying: Place the drying trays loaded with wet materials on the drying cart in order from top to bottom. After loading, push them into the drying oven, close the oven door, open the steam valve, start the circulating fan, control the drying temperature at 75-85℃, and the drying time is 4 hours. Record the oven temperature every 2 hours. S4: Grinding: Grind the dried granules into 30-60 mesh computer-controlled powder; S5: Total Mixing: Add the pulverized medicine powder into the three-dimensional mixer, add excipients to improve the flowability of the medicine powder, close the feeding port, turn on the three-dimensional mixer and mix for 20-50 minutes, then discharge to form a filling agent; S6: Filling: Prepare 100 or more capsule shells, including the capsule body and the capsule cap. Fill all the capsule shells with the filling agent. Weigh one side of the capsule every minute during the filling process and check at any time whether the filled capsules have rubbed edges, double caps, or empty capsules.

2. The preparation process for improving the filling quality of Xin'an capsules according to claim 1, characterized in that: In step S2, the thickness of the particles spread on the baking tray does not exceed 2.5 cm.

3. The preparation process for improving the filling quality of Xin'an capsules according to claim 2, characterized in that: The auxiliary materials used in step S5 consist of one or more of magnesium stearate, magnesium oxide, and liquid paraffin.

4. The preparation process for improving the filling quality of Xin'an capsules according to claim 3, characterized in that: The excipients used in step S5 account for 0.5-1.5% of the total drug amount.

5. The preparation process for improving the filling quality of Xin'an capsules according to claim 4, characterized in that: The steps also include S7: Filling volume difference detection. Take 10 filled capsules, accurately weigh each capsule, remove the capsule cap, pour out the contents without damaging the capsule shell, wipe the inside and outside clean with degreased cotton, and accurately weigh each capsule shell in turn, and record the weighing data.

6. The preparation process for improving the filling quality of Xin'an capsules according to claim 5, characterized in that: The step also includes S8: disintegration time limit detection, taking 6 filled capsules, using water as a medium, and recording the time it takes for the 6 capsules to completely disintegrate.

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