Levonorgestrel tablet and preparation method thereof

Abstract

The invention discloses a levonorgestrel tablet and a preparation method thereof. The levonorgestrel tablet is prepared from the following components: 0.75 part of levonorgestrel, 20 to 30 parts of lactose, 20 to 25 parts of corn starch, 0.8 to 1.0 part of corn starch slurry, 1 to 2 parts of colloidal silicon dioxide, 1 to 2 parts of talcum powder and 1 to 2 parts of magnesium stearate. The colloidal silicon dioxide provided by the invention can cooperate with the corn starch to help the tablet to be disintegrated more quickly in vivo, so that the release rate of the medicine is accelerated. The dissolution rate of the prepared levonorgestrel tablet reaches 65.6%-70.7% in 30 minutes, and the dissolution rate of the prepared levonorgestrel tablet reaches up to 86.0% in 60 minutes.

Description

Technical Field

[0001] The invention belongs to the field of medicine, and in particular relates to a levonorgestrel tablet and a preparation method thereof. Background Art

[0002] Levonorgestrel is a fast-acting, short-acting emergency contraceptive. It is the optically active part of norgestrel, and its activity is twice as strong as norgestrel. Accordingly, its usage can be reduced by half. As a potent oral progestin, levonorgestrel has a progestin effect that is about 5 to 10 times that of norgestrel, and has both androgenic, estrogenic and anti-estrogen activities. It can significantly inhibit ovulation and prevent the implantation of fertilized eggs, increase the consistency of cervical mucus to increase the resistance to sperm penetration, change the consistency of cervical mucus and inhibit the development of the endometrium. With these effects, it exerts a fast-acting contraceptive effect and is one of the most widely used contraceptives.

[0003] Levonorgestrel has low solubility in water and low bioavailability. Various solutions have been proposed in the prior art. For example, Chinese patent No. 201110120200.7 discloses a method for preparing a solid dispersion levonorgestrel tablet. The method first fully mixes levonorgestrel and a water-soluble carrier material, and adopts a melting method to prepare a levonorgestrel solid dispersion, followed by mixing and tableting with various auxiliary materials. Although the levonorgestrel tablet obtained by this method has good dissolution performance, its preparation process is cumbersome, and the melting process consumes a large amount of energy. In view of this, it is of great significance for the vast female population to study and explore new formula ratios to prepare levonorgestrel with good dissolution. Summary of the invention In view of the shortcomings of the prior art, the primary purpose of the present invention is to provide a levonorgestrel tablet. The raw materials of the levonorgestrel tablet of the present invention are easy to obtain, the component ratio is reasonable, and the dissolution performance of the prepared product is excellent.

[0004] Another object of the present invention is to provide a method for preparing the levonorgestrel tablets. The preparation method of the present invention is simple and easy to implement, energy-saving and environmentally friendly, and has good promotion prospects.

[0005] The purpose of the present invention is achieved through the following technical solutions: A levonorgestrel tablet is prepared from the following components: 0.75 parts of levonorgestrel, 20-30 parts of lactose, 20-25 parts of corn starch, 0.8-1.0 parts of corn starch slurry, 1-2 parts of colloidal silicon dioxide, 1-2 parts of talc and 1-2 parts of magnesium stearate.

[0006] Preferably, the levonorgestrel tablet is prepared from the following components: 0.75 parts of levonorgestrel, 20-25 parts of lactose, 28-25 parts of corn starch, 0.8 parts of corn starch slurry, 2 parts of colloidal silicon dioxide, 1-2 parts of talc and 1-2 parts of magnesium stearate.

[0007] Preferably, the levonorgestrel tablet is prepared from the following components: 0.75 parts of levonorgestrel, 22 parts of lactose, 28 parts of corn starch, 0.8 parts of corn starch slurry, 2 parts of colloidal silicon dioxide, 2 parts of talc and 1 part of magnesium stearate.

[0008] Preferably, the levonorgestrel tablet is α-crystalline levonorgestrel.

[0009] Preferably, the corn starch is pregelatinized starch.

[0010] Preferably, the mass fraction of corn starch slurry is 10-15%.

[0011] The preparation method of above-mentioned levonorgestrel tablets comprises the steps: (1) Fully mixing levonorgestrel, lactose and corn starch according to the component ratio to obtain a dry mix; (2) adding corn starch slurry to the dry blend, continuing to mix until uniform wet granules are formed, passing the wet granules through a granulator for granulation, and then drying and granulating the granulated samples; (3) The granulated sample is mixed with colloidal silicon dioxide, talc and magnesium stearate, and finally tabletted to prepare levonorgestrel tablets.

[0012] Preferably, in step (1), the particle size of levonorgestrel is 80-100 μm.

[0013] Preferably, in step (2), the drying temperature is 40-50° C., and the drying time is 0.5-1 h.

[0014] Preferably, in step (3), the tabletting pressure is 10-15 kN.

[0015] Compared with the prior art, the beneficial effects of the present invention include: In the present invention, corn starch and lactose are used as fillers together. On the other hand, corn starch has good water absorption. When the tablet contacts the liquid, corn starch will quickly absorb water and swell, generating mechanical force to promote the disintegration of the tablet. Colloidal silicon dioxide can cooperate with the effect of corn starch to help the tablet disintegrate faster in the body, thereby accelerating the release rate of the drug. DETAILED DESCRIPTION

[0016] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0017] The levonorgestrel used in the embodiment and the comparative example is α-crystalline levonorgestrel; the corn starch used is pregelatinized corn starch, and the corn starch slurry used is a pregelatinized corn starch slurry with a mass fraction of 10%.

[0018] Example 1 A levonorgestrel tablet is prepared from the following components: 0.75 parts of levonorgestrel, 20 parts of lactose, 20 parts of corn starch, 0.8 parts of corn starch slurry, 1 part of colloidal silicon dioxide, 1 part of talc and 1 part of magnesium stearate.

[0019] The preparation method of the above-mentioned levonorgestrel tablets comprises the following steps: (1) According to the component ratio, levonorgestrel, lactose and corn starch with a particle size of 80 to 100 μm are fully mixed to obtain a dry blend; (2) Add corn starch slurry to the dry blend, continue mixing until uniform wet granules are formed, granulate the wet granules through a granulator, and then dry and granulate the granulated sample at a drying temperature of 50° C. for 30 min.

[0020] (3) The granulated sample is mixed with colloidal silicon dioxide, talc and magnesium stearate, and finally tabletted under a pressure of 15 kN to prepare the levonorgestrel tablets.

[0021] Example 2 A levonorgestrel tablet is prepared from the following components: 0.75 parts of levonorgestrel, 22 parts of lactose, 28 parts of corn starch, 0.8 parts of corn starch slurry, 2 parts of colloidal silicon dioxide, 2 parts of talc and 1 part of magnesium stearate.

[0022] The preparation method of the above-mentioned levonorgestrel tablets comprises the following steps: (1) Fully mixing levonorgestrel, lactose and corn starch according to the component ratio to obtain a dry mix; (2) Add corn starch slurry to the dry blend, continue mixing until uniform wet granules are formed, granulate the wet granules through a granulator, and then dry and granulate the granulated sample at a drying temperature of 50° C. for 30 min.

[0023] (3) The granulated sample is mixed with colloidal silicon dioxide, talc and magnesium stearate, and finally tabletted under a pressure of 15 kN to prepare the levonorgestrel tablets.

[0024] Example 3 A levonorgestrel tablet is prepared from the following components: 0.75 parts of levonorgestrel, 25 parts of lactose, 25 parts of corn starch, 0.8 parts of corn starch slurry, 2 parts of colloidal silicon dioxide, 2 parts of talc and 2 parts of magnesium stearate.

[0025] The preparation method of the above-mentioned levonorgestrel tablets comprises the following steps: (1) Fully mixing levonorgestrel, lactose and corn starch according to the component ratio to obtain a dry mix; (2) Add corn starch slurry to the dry blend, continue mixing until uniform wet granules are formed, pass the wet granules through a granulator for granulation, and then dry and granulate the granulated sample.

[0026] (3) The granulated sample is mixed with colloidal silicon dioxide, talc and magnesium stearate, and finally tabletted to prepare the levonorgestrel tablets.

[0027] Comparative Example 1 A levonorgestrel tablet is prepared from the following components: 0.75 parts of levonorgestrel, 22 parts of lactose, 28 parts of corn starch, 0.8 parts of corn starch slurry, 2 parts of talc and 1 part of magnesium stearate.

[0028] The preparation method of the above-mentioned levonorgestrel tablets comprises the following steps: (1) Fully mixing levonorgestrel, lactose and corn starch according to the component ratio to obtain a dry mix; (2) Add corn starch slurry to the dry blend, continue mixing until uniform wet granules are formed, granulate the wet granules through a granulator, and then dry and granulate the granulated sample at a drying temperature of 50° C. for 30 min.

[0029] (3) The granulated sample is mixed with talc and magnesium stearate, and finally tabletted under a pressure of 15 kN to prepare the levonorgestrel tablets.

[0030] Comparative Example 2 A levonorgestrel tablet is prepared from the following components: 0.75 parts of levonorgestrel, 22 parts of lactose, 28 parts of corn starch, 0.8 parts of corn starch slurry, 0.5 parts of colloidal silicon dioxide, 2 parts of talc and 1 part of magnesium stearate.

[0031] The preparation method of the above-mentioned levonorgestrel tablets comprises the following steps: (1) Fully mixing levonorgestrel, lactose and corn starch according to the component ratio to obtain a dry mix; (2) Add corn starch slurry to the dry blend, continue mixing until uniform wet granules are formed, granulate the wet granules through a granulator, and then dry and granulate the granulated sample at a drying temperature of 50° C. for 30 min.

[0032] (3) The granulated sample is mixed with colloidal silicon dioxide, talc and magnesium stearate, and finally tabletted under a pressure of 15 kN to prepare the levonorgestrel tablets.

[0033] Dissolution Testing Take the levonorgestrel tablets prepared in Examples 1 to 3 and Comparative Examples 1 to 2, and perform a dissolution test on them. The specific steps are as follows: According to the third method of Appendix XC of Part II of the 2005 edition of the Chinese Pharmacopoeia, 250 mL of 0.8% sodium dodecyl sulfate solution was used as the dissolution medium, the speed was 50 rpm, and samples were taken at 10 min, 20 min, 30 min, 45 min and 60 min to calculate the cumulative dissolution. The test results are shown in Table 1.

[0034] Table 1 Dissolution results

[0035] As can be seen from Table 1, the dissolution of the levonorgestrel tablets prepared by the preparation method of the present invention reached 65.6% to 70.7% at 30 minutes. Comparative Example 1 does not contain colloidal silicon dioxide, and the dissolution of the levonorgestrel tablets prepared at the same dissolution time is only 52.6%. After adding a small amount of colloidal silicon dioxide, the dissolution of Comparative Example 2 at 30 minutes is significantly improved compared with Comparative Example 1, but still lower than the dissolution of the present invention. The applicant believes that this may be because colloidal silicon dioxide can cooperate with the disintegration of corn starch, thereby enhancing the dissolution effect of the medicament and improving the dissolution rate.

[0036] The specific implementation of the present invention described above does not constitute a limitation on the protection scope of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A levonorgestrel tablet, characterized in that: The invention is prepared from the following components: 0.75 parts of levonorgestrel, 20-30 parts of lactose, 20-25 parts of corn starch, 0.8-1.0 parts of corn starch slurry, 1-2 parts of colloidal silicon dioxide, 1-2 parts of talc and 1-2 parts of magnesium stearate.

2. The levonorgestrel tablet according to claim 1, characterized in that The invention is prepared from the following components: 0.75 parts of levonorgestrel, 20-25 parts of lactose, 28-25 parts of corn starch, 0.8 parts of corn starch slurry, 2 parts of colloidal silicon dioxide, 1-2 parts of talc and 1-2 parts of magnesium stearate.

3. The levonorgestrel tablet according to claim 2, characterized in that Prepared from ingredients including: 0.75 parts levonorgestrel, 22 parts lactose, 28 parts corn starch, 0.8 parts corn starch slurry, 2 parts colloidal silicon dioxide, 2 parts talc and 1 part magnesium stearate.

4. The levonorgestrel tablet according to any one of claims 1 to 3, characterized in that The levonorgestrel tablet is α-crystalline levonorgestrel.

5. The levonorgestrel tablet according to claim 4, characterized in that: The corn starch is pregelatinized starch.

6. The levonorgestrel tablet according to claim 5, characterized in that: The mass fraction of the corn starch slurry is 10-15%.

7. The method for preparing the levonorgestrel tablets according to any one of claims 1 to 6, characterized in that: The steps include: (1) Fully mixing levonorgestrel, lactose and corn starch according to the component ratio to obtain a dry mix; (2) adding corn starch slurry to the dry blend, continuing to mix until uniform wet granules are formed, granulating the wet granules through a granulator, and then drying and granulating the granulated sample; (3) The granulated sample is mixed with colloidal silicon dioxide, talc and magnesium stearate, and finally tabletted to prepare the levonorgestrel tablets.

8. The method for preparing levonorgestrel tablets according to claim 7, characterized in that: The particle size of the levonorgestrel in step (1) is 80-100 μm.

9. The method for preparing levonorgestrel tablets according to claim 7, characterized in that: The drying temperature in step (2) is 40-50° C., and the drying time is 0.5-1 h.

10. The method for preparing the levonorgestrel tablets according to claim 7, characterized in that: The tabletting pressure in step (3) is 10-15 kN.

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