Preparation method of epalrestat oral tablet and oral tablet

Abstract

The invention belongs to the field of pharmaceutical preparations, and particularly relates to an epalrestat oral tablet preparation method and an oral tablet. A brown coating material added with brown iron oxide is adopted for coating, so that the light stability of the epalrestat tablet is improved under the condition of low coating weight gain.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations, and particularly relates to a preparation method of an epalrestat oral tablet and the oral tablet. Background Art

[0002] Patent CN114762683A describes a drug composition for treating diabetic neuropathy and a preparation method thereof, which is characterized in that the product is prepared by fluidized bed granulation. The product prepared according to this patent may have a slower dissolution curve under high temperature and accelerated conditions.

[0003] Patent CN115245496A describes a method for preparing a stable epalrestat tablet, which is characterized in that first, part of the excipients and the raw material are wet granulated into granules, and after drying the granules, they are wet granulated again with the remaining excipients, and then dried again. The process is relatively complicated, requiring two wet granulations, drying and granulation, and the coating weight gain is about 10%, the coating time is long, and the entire production process is time-consuming.

[0004] The epalrestat preparations prepared by the prior art generally have a phenomenon of slow dissolution curve under high temperature conditions and accelerated conditions; due to the poor photostability of epalrestat, there is generally a high coating weight gain and a long coating time, which makes the entire production process time-consuming. Summary of the invention

[0005] In order to solve the above problems, the present invention provides a method for preparing an epalrestat oral tablet and an oral tablet, which is coated with a brown film coating premix, and the problem of poor light stability of the product can be solved at a low coating weight gain. Specifically, the method for preparing an epalrestat oral tablet comprises the following steps:

[0006] Granulation: weighing hydroxypropyl methylcellulose, epalrestat, mannitol, low-substituted hydroxypropyl cellulose and magnesium stearate according to the weight ratio, granulating and mixing to obtain mixed granules;

[0007] Tableting, placing the total mixed granules into a concave punch die for tableting to obtain tablets;

[0008] Coating: Add brown film coating premix into aqueous solution and stir to dissolve, prepare coating solution, coat the tablets and dry.

[0009] Optionally, the granulation comprises:

[0010] adding the hypromellose into an aqueous solution and dissolving it to obtain a binder solution;

[0011] After mixing the epalrestat, the mannitol and a portion of the low-substituted hydroxypropyl cellulose, water is added to moisten the mixture to obtain a wet material;

[0012] The wet material is transferred to a fluidized bed, and the binder solution is sprayed into the fluidized bed for granulation. After drying and granulation, the remaining low-substituted hydroxypropyl cellulose and the magnesium stearate are added for total mixing to obtain the total mixed granules.

[0013] Optionally, the concave punch is a circular shallow concave punch.

[0014] Optionally, the tablet hardness is controlled at 70 to 110N during tableting.

[0015] Optionally, the material temperature during coating is 35-45°C.

[0016] Optionally, the drying time is 5 to 10 minutes.

[0017] Optionally, the mixing of the epalrestat, the mannitol and a portion of the low-substituted hydroxypropyl cellulose and adding water to wet the mixture to obtain a wet material comprises:

[0018] The epalrestat, the mannitol and a portion of the low-substituted hydroxypropyl cellulose are mixed and moistened in a wet granulation pot to obtain the wet material.

[0019] Furthermore, the present invention also provides an epalrestat oral tablet, which is prepared by any of the preparation methods described above.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The film coating premix is ​​brown in color and has good light-shielding properties, which can improve the light stability of epalrestat tablets at low coating weight gain.

[0022] Based on the following detailed description of specific embodiments of the present invention in conjunction with the accompanying drawings, those skilled in the art will become more aware of the above and other objects, advantages and features of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 is a comparison diagram of the dissolution curves of the embodiment at 0 day and at high temperature for 30 days;

[0024] Figure 2 This is a comparison of the dissolution curves of Comparative Example 1 at 0 days and 30 days at high temperature;

[0025] Figure 3 This is a comparison of the dissolution curves of Comparative Example 2 at 0 days and 30 days at high temperature; DETAILED DESCRIPTION

[0026] The following describes a method for preparing an epalrestat oral tablet and an oral tablet according to an embodiment of the present invention. In the description of this embodiment, it should be understood that the terms "first" and "second" are used for descriptive purposes only, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features, that is, include one or more of the features. In the description of the present invention, the meaning of "multiple" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined. When a feature "includes or contains" one or some of the features it covers, unless otherwise specifically described, this indication does not exclude other features and may further include other features.

[0027] In the description of the present embodiment, the description with reference to the terms "one embodiment", "some embodiments", "illustrative embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials, or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0028] In some embodiments of the present invention, a method for preparing an epalrestat oral tablet is provided, the method comprising the following steps:

[0029] Step S10, granulation, weighing hydroxypropyl methylcellulose, epalrestat, mannitol, low-substituted hydroxypropyl cellulose and magnesium stearate according to the weight ratio, granulating and mixing to obtain mixed granules;

[0030] Step S20, tableting, placing the total mixed granules into a concave punch die for tableting to obtain tablets;

[0031] Step S30, coating, adding the brown film coating premix into the aqueous solution and stirring to dissolve, preparing the coating solution, coating the tablets and drying them.

[0032] Specifically, first, hydroxypropyl methylcellulose, epalrestat, mannitol, low-substituted hydroxypropyl cellulose and magnesium stearate are weighed according to a weight ratio and mixed to obtain a total mixed granule. Secondly, the total mixed granule is punched to obtain a tablet. Finally, the tablet is coated with a brown film coating premix. Thus, an epalrestat tablet that can be taken orally is obtained.

[0033] In this example, the epalrestat tablets were coated with a brown film coating premix, so that the photostability of epalrestat could be improved at a low coating weight gain.

[0034] In some embodiments of the invention, granulation comprises:

[0035] Step S11, adding hypromellose into the aqueous solution to dissolve it, to obtain a binder solution;

[0036] Step S12, mixing epalrestat, mannitol and a portion of low-substituted hydroxypropyl cellulose, and adding water to moisten the mixture to obtain a wet material;

[0037] Step S13, transferring the wet material to a fluidized bed, spraying the binder solution into the fluidized bed for granulation, and after drying the granules, adding the remaining low-substituted hydroxypropyl cellulose and magnesium stearate for total mixing to obtain total mixed granules.

[0038] In this embodiment, before granulation, epalrestat, mannitol and part of low-substituted hydroxypropyl cellulose are mixed, and then water is added to moisten the mixture to obtain a wet material, which can reduce or eliminate the segregation phenomenon caused by the difference in particle size and density in the mixture.

[0039] In some embodiments of the present invention, the concave die is a circular shallow concave die. In this embodiment, the circular shallow concave die is selected to increase the surface area of ​​the tablet, accelerate the absorption rate, further improve the patient's experience, and improve compliance.

[0040] In some embodiments of the present invention, the tablet hardness is controlled at 70-110N during tableting. Specifically, the tablet hardness can be any value between 70-110, such as 70N, 85N, 90N, 100N, etc. In this embodiment, the tablet hardness is controlled at 70-110N during tableting, which can avoid the tablet hardness being too low, resulting in insufficient tablet texture, easy to break or deform; and can also avoid the tablet hardness being too high, resulting in difficulty in dissolution or absorption.

[0041] In some embodiments of the present invention, the material temperature during coating is 35-45°C. At a higher temperature, the droplets of the coating solution evaporate more quickly, and the coating can be performed at a higher spray speed, which can shorten the coating time and improve the efficiency of the coating. However, too high a temperature may cause the coating solution to dry out, affecting the coating efficiency and the appearance of the coated tablets.

[0042] In this embodiment, the material temperature is controlled between 35 and 45°C during coating, such as 35°C, 40°C, 44°C, 45°C, etc., which can not only avoid spray drying of the coating liquid, but also make the coating liquid evaporate quickly, thereby improving the efficiency of coating.

[0043] In some embodiments of the present invention, the drying time is 5 to 10 minutes.

[0044] In some embodiments of the present invention, the above-mentioned mixing of epalrestat, mannitol and part of low-substituted hydroxypropyl cellulose and then adding water to moisten to obtain a wet material comprises: mixing and moistening epalrestat, mannitol and part of low-substituted hydroxypropyl cellulose in a wet granulation pot to obtain a wet material.

[0045] In this embodiment, mixing and wetting are performed in a wet granulation pot, which can improve the granulation efficiency.

[0046] Furthermore, the present invention also provides an epalrestat oral tablet, which is prepared by the preparation method in any one of the above embodiments.

[0047] The present invention is specifically explained below using several embodiments, and the technical solutions in the embodiments of the present invention are clearly and completely described. The described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments.

[0048] Example 1

[0049] A method for preparing epalrestat oral tablets comprises the following steps:

[0050] Step S101, weighing 38.5 g of hypromellose as a binder, adding it into an aqueous solution to dissolve it, and preparing a binder solution;

[0051] Step S102, weigh 500 g of epalrestat, 506.5 g of mannitol and 14 g of low-substituted hydroxypropyl cellulose, mix them, and add a small amount of water to moisten them.

[0052] Step S103, the wet material is transferred to a fluidized bed, and the binder solution is sprayed into the granules for granulation. After drying and granulation, 14 g of low-substituted hydroxypropyl cellulose and 11 g of magnesium stearate are added for total mixing to obtain total mixed granules.

[0053] Step S104, using a 6.1 mm circular shallow concave punch to press a tablet, controlling the tablet weight to 108.4 mg and the tablet hardness to 90 N, to obtain a circular tablet.

[0054] Step S105, weigh 30g of film coating premix (brown), add it to the aqueous solution and stir to dissolve, to prepare the coating solution. Control the coating material temperature at 40°C and perform coating. After coating, dry for 7 minutes.

[0055] It should be noted that the coating composition of each epalrestat oral tablet is 0.5 mg titanium dioxide, 2.0 mg hydroxypropyl cellulose, 0.2 mg polyethylene glycol and 0.3 mg brown iron oxide, a total of 3.0 mg / tablet.

[0056] Comparative Example 1

[0057] A method for preparing an epalrestat oral tablet comprises the following steps: step S201, weighing 38.5 g of hypromellose as a binder, adding it into an aqueous solution to dissolve it, and preparing a binder solution;

[0058] Step S202, weigh 500 g of epalrestat, 506.5 g of mannitol and 14 g of low-substituted hydroxypropyl cellulose, mix them, and add a small amount of adhesive solution to moisten them.

[0059] Step S203, the wet material is transferred to a fluidized bed, and the binder solution is sprayed into the granules for granulation. After drying and granulation, 14 g of low-substituted hydroxypropyl cellulose and 11 g of magnesium stearate are added for total mixing to obtain total mixed granules.

[0060] Step S204, using a 6.1 mm circular shallow concave punch to press a tablet, controlling the tablet weight to 108.4 mg and the tablet hardness to 90 N, to obtain a circular tablet.

[0061] Step S205, weigh 30g of film coating premix (brown), add it to the aqueous solution and stir to dissolve, to prepare the coating solution. Control the coating material temperature at 40°C and perform coating. After coating, dry for 7 minutes.

[0062] Comparative Example 2

[0063] A method for preparing epalrestat oral tablets comprises the following steps:

[0064] Step S301, weighing 38.5 g of hypromellose as a binder, adding it into an aqueous solution to dissolve it, and preparing a binder solution;

[0065] Step S302, weigh 500 g of epalrestat, 506.5 g of mannitol and 14 g of low-substituted hydroxypropyl cellulose, mix them, add the binder solution and granulate to obtain wet granules.

[0066] Step S303, the wet granules are transferred to a fluidized bed, and after drying and granulation, 14 g of low-substituted hydroxypropyl cellulose and 11 g of magnesium stearate are added for total mixing to obtain total mixed granules.

[0067] Step S304, using a 6.1 mm circular shallow concave punch to press a tablet, controlling the tablet weight to 108.4 mg and the tablet hardness to 90 N, to obtain a circular tablet.

[0068] Step S305, weigh 30g of film coating premix (brown), add it to the aqueous solution and stir to dissolve, to prepare the coating solution. Control the coating material temperature at 40°C and perform coating. After coating, dry for 7 minutes.

[0069] Comparative Example 3

[0070] A method for preparing epalrestat oral tablets comprises the following steps:

[0071] The difference from Example 1 is the coating composition: the coating composition of each epalrestat oral tablet is 3.3 mg titanium dioxide, 5.0 mg hydroxypropyl cellulose, and 2.7 mg poloxamer, a total of 11.0 mg / tablet.

[0072] Comparative Example 4

[0073] A method for preparing epalrestat oral tablets comprises the following steps:

[0074] The difference from Example 1 is the coating composition: the coating composition of each epalrestat oral tablet is 4.0 mg titanium dioxide, 3.0 mg hydroxypropyl cellulose, 0.3 mg talc, and 1.5 mg polyethylene glycol, a total of 9.0 mg / tablet.

[0075] Comparative Example 5

[0076] A method for preparing epalrestat oral tablets comprises the following steps:

[0077] The difference from Example 1 is the coating composition: the coating composition of each epalrestat oral tablet is 0.3 mg titanium dioxide, 1.3 mg hydroxypropyl cellulose, 0.1 mg polyethylene glycol and 0.2 mg brown iron oxide, a total of 1.9 mg / tablet.

[0078] The products prepared in Example, Comparative Example 1 and Comparative Example 2 were placed at a high temperature of 60° C. for 30 days, and their dissolution curves were tested. The following are the experimental data for 0 days and 30 days at high temperature as shown in Tables 1 and 2.

[0079] Table 1 Dissolution profile of epalrestat oral tablets after 0 days of storage

[0080]

[0081] Table 2 Dissolution profile of epalrestat oral tablets after 30 days of storage

[0082]

[0083] Compared with the embodiment, the dissolution curves of the products prepared by the production processes of Comparative Examples 1 and 2 slowed down under high temperature conditions.

[0084] The tablets prepared in the example were coated with no coating material, placed under light conditions for 10 days, and the related substances were detected. The uncoated tablets were used as reference preparations, and the impurity D was the photodegradation impurity of the raw material. The impurity D detection data was used to evaluate the light-shielding property of the coating material. The obtained data are as follows:

[0085] Table 3 Evaluation of light-shielding properties of different coated tablets

[0086]

[0087] Compared with the examples, in Comparative Examples 3 and 4, the amount of impurity D detected under the conditions of 10 days of light exposure was still higher than that of the reference preparation when different coating compositions, high coating weight gain and high dosage of titanium dioxide were used, and after adding brown iron oxide to the coating material, even at a coating weight gain of about 2 mg / tablet, the impurity D was still undetectable under the conditions of 10 days of light exposure (Comparative Example 5). After adding brown iron oxide to the coating material, its light-shielding property was excellent.

Claims

1. A method for preparing an epalrestat oral tablet, characterized in that: The following steps are involved: Granulation: weighing hydroxypropyl methylcellulose, epalrestat, mannitol, low-substituted hydroxypropyl cellulose and magnesium stearate according to the weight ratio, granulating and mixing to obtain mixed granules; Tableting, placing the total mixed granules into a concave punch die for tableting to obtain tablets; Coating: Add brown film coating premix into aqueous solution and stir to dissolve, prepare coating solution, coat the tablets and dry.

2. The method for preparing epalrestat oral tablets according to claim 1, characterized in that: The granulation comprises: adding the hypromellose into an aqueous solution and dissolving it to obtain a binder solution; After mixing the epalrestat, the mannitol and a portion of the low-substituted hydroxypropyl cellulose, water is added to moisten the mixture to obtain a wet material; The wet material is transferred to a fluidized bed, and the binder solution is sprayed into the fluidized bed for granulation. After drying and granulation, the remaining low-substituted hydroxypropyl cellulose and the magnesium stearate are added for total mixing to obtain the total mixed granules.

3. The method for preparing epalrestat oral tablets according to claim 1, characterized in that: The concave punching die is a circular shallow concave punching die.

4. The method for preparing epalrestat oral tablets according to claim 1, characterized in that: During tableting, the tablet hardness is controlled at 70-110N.

5. The method for preparing epalrestat oral tablets according to claim 1, characterized in that: The coating material temperature is 35-45°C.

6. The method for preparing epalrestat oral tablets according to claim 1, characterized in that: The drying time is 5 to 10 minutes.

7. The method for preparing epalrestat oral tablets according to claim 2, characterized in that: The method of mixing the epalrestat, the mannitol and a portion of the low-substituted hydroxypropyl cellulose, and adding water to wet the mixture to obtain a wet material comprises: The epalrestat, the mannitol and a portion of the low-substituted hydroxypropyl cellulose are mixed and moistened in a wet granulation pot to obtain the wet material.

8. An epalrestat oral tablet, characterized in that: The preparation is obtained by the preparation method described in any one of claims 1 to 7.

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