Method capable of accelerating dissolution rate of praziquantel in water

Abstract

The invention discloses a preparation method of praziquantel soluble powder, a liquid preparation and other dosage forms. According to the method, lactose, poloxamer, PVP (Polyvinyl Pyrrolidone) or PVA (Polyvinyl Alcohol) are used for preparing praziquantel soluble powder or a liquid preparation and other dosage forms. According to the scheme, the praziquantel preparation which is low in cost, easy and convenient to operate, high in dissolving speed and good in stability is provided.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical preparations, and specifically relates to a preparation technology of praziquantel, which is mainly used for preparing solid preparations such as soluble powders with fast dissolution speed or good stability, and liquid preparations thereof. Background Art

[0002] As a new broad-spectrum antiparasitic drug, praziquantel has been widely used in clinical medicine. Praziquantel is effective against diseases such as Schistosoma japonicum, Schistosoma mansoni and Schistosoma haematobium, Clonorchis sinensis, Paragonimus, Fasciola zingiberensis, tapeworms and cysticercosis. Taking animal drugs as an example, at present (20230908), there are 433 approval numbers for praziquantel in Chinese veterinary drugs, including only three dosage forms: tablets (0.1g), premix 2% (for aquaculture) and powder (50%), with a single dosage form. Although in recent years, a variety of new dosage forms such as liposomes, microspheres, transdermal preparations, injections, suppositories, implants, etc. have appeared in patents and journals, using new technologies such as inclusion, emulsification, liposomes, nanoparticles, etc., but most preparations are still in the basic research or preclinical research stage.

[0003] At room temperature, the solubility of praziquantel raw material in water is about 0.26 mg / mL, and the dissolution rate is slow. Research results show that the release concentration of raw material praziquantel is only equivalent to dissolving 1 mg in about 90 ml of aqueous release medium 1 hour after the release experiment. After oral administration of ordinary preparations of praziquantel, the dissolution rate is slow, the absorption rate is high, and it has a significant first-pass effect in the liver. Therefore, the amount of praziquantel that enters the blood circulation and escapes liver metabolism after oral administration is small, which seriously affects the efficacy. At the same time, due to the solubility and dissolution rate of praziquantel, it cannot meet the needs of real users for the use of praziquantel preparations. Moreover, current research is mainly focused on improving the solubility of praziquantel, and there is little research on how to use low-cost excipients or methods to increase the dissolution rate of praziquantel. Summary of the invention

[0004] In view of the above situation, in order to overcome the defects of the prior art, one of the purposes of the present invention is to provide a low-cost, easy-to-operate, fast-dissolving method for praziquantel solubilization, so as to solve the cost and industrialization difficulties of the current praziquantel solubilization technology.

[0005] One method for achieving the purpose is to mix praziquantel with an appropriate amount of lactose, poloxamer, povidone (PVP) or a mixture thereof to prepare a solid preparation such as a soluble powder, or use it to dissolve a liquid preparation.

[0006] The second purpose of the present invention is to provide a prescription and method of use of a high-dissolution-rate praziquantel preparation. The ratio of praziquantel to the above-mentioned solid excipients should be 1:0.2 or more, and the preferred ratio is 1:0.8 or more. Among them, generally, while ensuring good dispersibility, the greater the proportion of solid excipients, the more the encapsulation effect and dissolution rate of the preparation can be ensured. When preparing an aqueous dispersion or using a water-soluble powder, first heat the water (50-100°C, preferably 80-100°C), add the mixed drug preparation, and stir and disperse until the praziquantel precipitate completely disappears. The liquid is placed at room temperature and gradually cooled to room temperature. Thereby, a liquid preparation of praziquantel is prepared. The liquid preparation prepared by this method is also made into a powder by freeze drying or spray drying, etc., for the preparation of preparations such as soluble powders.

[0007] The third object of the present invention is to use the above technology as a basis for further preparing various suitable praziquantel preparations in the later stage. The preparations prepared by the above technology and method can not only prepare aqueous liquids, films, suppositories, gels, water-soluble powders, etc., but also can use the praziquantel powder prepared from the source by the above method to further prepare various solid and semi-solid dosage forms, such as capsules, powders, tablets, granules, pills, etc.

[0008] In summary, the advantages of the present invention are to provide a praziquantel preparation scheme with low cost, rapid industrialization, simple operation, fast dissolution speed or good stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 The dissolution of praziquantel raw material and praziquantel raw material with the same amount of lactose added under the same experiment. DETAILED DESCRIPTION

[0010] The present invention is further described in detail below in conjunction with embodiments and drawings, but the embodiments of the present invention are not limited thereto.

[0011] Example 1: Weigh 25 mg of praziquantel and 25 mg of lactose, mix them, stir and dissolve them in 50 mL of boiling water, cool them to room temperature, and obtain a praziquantel aqueous solution with a concentration of approximately 0.5 mg / ml. Take a photo after stirring for about 4 minutes. See attached photo Figure 1 A.

[0012] Example 2: Weigh 25 mg of praziquantel and 25 mg of poloxamer 188, mix them evenly, stir and dissolve them in 50 mL of boiling water, cool them to room temperature, and obtain a praziquantel aqueous solution with an approximate concentration of 0.5 mg / ml.

[0013] Example 3: Weigh 25 mg of praziquantel and 25 mg of PVA1788, mix them evenly, stir and dissolve them in 50 mL of boiling water, and cool them to room temperature to obtain an aqueous solution of praziquantel with an approximate concentration of 0.5 mg / ml.

[0014] Example 4: Weigh 25 mg of praziquantel and 25 mg of PVP-K30, mix them, stir and dissolve them in 50 mL of boiling water, cool them to room temperature, and obtain an aqueous solution of praziquantel with an approximate concentration of 0.5 mg / ml.

[0015] Example 5: Weigh 25 mg of praziquantel and 50 mg of lactose, mix them, stir and dissolve them in 50 mL of boiling water, cool them to room temperature, and obtain an aqueous solution of praziquantel with an approximate concentration of 0.5 mg / ml.

[0016] Example 6: Weigh praziquantel and mix it evenly with an equal amount of lactose to obtain a soluble powder with a praziquantel content of 50%.

[0017] Example 7: Weigh praziquantel and mix it evenly with an equal amount of poloxamer 188 to obtain a soluble powder with a praziquantel content of 50%.

[0018] Example 8: Weigh praziquantel and mix it evenly with an equal amount of PVP-K30 to obtain a soluble powder with a praziquantel content of 50%.

[0019] Example 9: Weigh praziquantel and mix it evenly with an equal amount of PVA1788 to obtain a soluble powder with a praziquantel content of 50%.

[0020] The representative embodiments mentioned above will be selected below to conduct relevant experiments to illustrate the characteristics and advantages of this technology.

[0021] Experimental Example 1 Comparison of Dissolution Rate and Stability Time of Preparations

[0022] First, two control preparations were prepared: Control preparation 1: 25 mg of praziquantel was weighed, stirred and dissolved in 50 mL of boiling water, cooled to room temperature, and the time required for stirring until complete dissolution was recorded.

[0023] Comparative preparation 2: Weigh 25 mg of praziquantel, stir and disperse it in 50 mL of water (90°C), and take a photo after stirring for 4 minutes. See attached photo Figure 1 B.

[0024] Then, the same method was used to examine the stirring and dissolution time of 50 mg of soluble powder of Examples 6-9 in 50 mL of boiling water. As shown in Table 1, the dissolution time of the four examples was shortened compared with the control preparation, especially the effect of lactose was very significant. However, from the perspective of the stability time of the solution, the preparation with PVP-K30 added had a longer solution stability time, followed by the preparation with poloxamer or PVA. Lactose has little effect on increasing the solution stability time.

[0025] Table 1 Dissolution time of preparations (n=3)

[0026]

[0027] Experimental Example 2: Praziquantel heating stability test

[0028] Example 1-4 was boiled, maintained at 100°C, and samples were taken at regular intervals to determine the praziquantel content using the established ultraviolet spectrophotometry. The results showed that within 4 hours, the absorbance of Example 1-4 at 263 nm did not decrease compared to that at 0. This result shows that the prepared praziquantel preparation has good tolerance to heating.

[0029] Experimental Example 3 Dilution Experiment

[0030] The same volume of water was added to the experimental examples 1-4 and after dilution, the stability was good and no insolubility occurred after further dilution, which indicated that the preparation could tolerate dilution.

[0031] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A method for promoting the dissolution rate of praziquantel, characterized in that: An appropriate amount of auxiliary materials is added to the praziquantel raw material, and the auxiliary materials specifically refer to lactose, poloxamer, povidone or a mixture thereof. Among them, a high proportion of excipients is conducive to the rapid dissolution of praziquantel in the preparation. The mass ratio of excipients to praziquantel in general preparations should be greater than 0.3:

1.

2. The preparation of the praziquantel solution preparation according to claim 1, characterized in that: Praziquantel is mixed with lactose, poloxamer, povidone or a mixture thereof, and the dissolution is promoted by heating and stirring, so that a praziquantel solution with a higher concentration can be obtained.

3. The use according to claims 1-2, characterized in that: Lactose has a good effect on improving the dissolution rate of praziquantel.

4. The use according to claims 1-3, characterized in that: The addition of PVP K30 can enhance the physical stability of praziquantel solution.

5. The use according to claims 1-4, characterized in that: Other excipients can be added to the prescription as needed to achieve the purpose of accelerating dissolution, improving solubility and drug stability.

6. The use according to claims 1-5, characterized in that: By using the above technology and method, not only water-soluble powder and aqueous liquid of praziquantel can be prepared, but also film, suppository, gel, and other dosage forms such as capsule, powder, tablet, granule, pill, etc. can be prepared.

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