Search

CN-121971395-A - Compound Florana chewable tablet and preparation method thereof

CN121971395ACN 121971395 ACN121971395 ACN 121971395ACN-121971395-A

Abstract

The invention discloses a compound Flirana chewable tablet and a preparation method thereof, and relates to the technical field of veterinary medicine preparations, wherein the chewable tablet consists of fluo Lei Lana, thiopyrimidine and moxidectin solid dispersoid constructed by poloxamer 407/sodium dodecyl sulfate (or sodium dodecyl sulfonate), and the preferable particle size D50 of the dispersoid is 5-30 mu m, and D90 is less than or equal to 80 mu m. The preparation process includes the steps of forming clear solution of moxidec Ding Yu, decompression drying, low temperature grinding, sieving to obtain dispersion, pre-mixing with microcrystalline cellulose, mixing with lactose, adding disintegrant and lubricant, and pre-pressing to form tablet. The system can maintain the amorphous distribution of moxidectin in the tablet, remarkably improve content uniformity, dissolution and acceleration stability, and form broad-spectrum synergy with fluorine Lei Lana and thiopyrimidine, and is suitable for killing fleas and ticks, treating roundworms and hookworms and preventing heartworms and tubular line diseases of dogs.

Inventors

  • LI XI
  • ZHU HONGHAO
  • JIANG KE
  • LI CONGYU
  • Liang Futong

Assignees

  • 湖南尚成生物科技有限公司

Dates

Publication Date
20260505
Application Date
20260407

Claims (9)

  1. 1. The compound fluororalrana chewable tablet is characterized by comprising, by weight, 25-600 parts of fluorine Lei Lana-600 parts of thiopyrimidine 12.5-300 parts of moxidectin solid dispersion 5-350 parts of filler 40-300 parts of disintegrating agent 0.5-25 parts of lubricant 1-50 parts of optional antioxidant 0.2-2 parts of corrective and 1-50 parts of flavoring agent; The moxidectin solid dispersion is prepared by mixing moxidectin and poloxamer 407 and in the presence of sodium dodecyl sulfate and/or sodium dodecyl sulfate, and the particle size of the solid dispersion D 50 is 20-80 mu m.
  2. 2. The compound fluororalston chewable tablet according to claim 1, wherein the mass ratio of moxidectin, poloxamer 407 and sodium dodecyl sulfate and/or sodium dodecyl sulfonate is 1:180-220:0.6-1.
  3. 3. The compound fluororalston chewable tablet according to claim 1, wherein the moxidectin solid dispersion has a particle size distribution D 50 -30 μm and D 90 -80 μm.
  4. 4. The compound fluororalston chewable tablet according to claim 1, wherein the filler is selected from one or more of microcrystalline cellulose, lactose, mannitol or pregelatinized starch.
  5. 5. The compound fluororalston chewable tablet according to claim 4, wherein the filler is microcrystalline cellulose and lactose with a mass ratio of 1.0-1.5:3, wherein moxidec Ding Jingbo poloxamer 407 and sodium dodecyl sulfate are treated to form a solid dispersion, and the solid dispersion is mixed with microcrystalline cellulose and then lactose during tabletting.
  6. 6. The compound fluororalston chewable tablet according to claim 5, wherein moxidectin exists in an amorphous solid state in the chewable tablet finished product, and no characteristic diffraction peak of moxidectin bulk drug appears in a range of 2Θ=5° -40 ° by powder X-ray diffraction.
  7. 7. The compound fluororalston chewable tablet according to claim 1, wherein the disintegrant is one or more selected from crospovidone, croscarmellose sodium, sodium carboxymethyl starch or dry starch.
  8. 8. The preparation method of the compound fluororalston chewable tablet is characterized by comprising the following steps of: (1) The preparation method of the moxidectin solid dispersion comprises the steps of dissolving sodium dodecyl sulfate in purified water, adding poloxamer 407, stirring and dissolving, adding moxidectin to form a clear solution, controlling the solid content of the solution to be 5-15% (w/w), regulating the pH value to be 6.0-7.5, concentrating the obtained solution under reduced pressure at the temperature of 40-50 ℃ and the vacuum degree of less than or equal to-0.08 MPa, continuously carrying out secondary vacuum drying at the temperature of 45 ℃ for 8-10 hours and obtaining a dried product, and grinding the dried product at low temperature and sieving the ground product with a 80-100-mesh sieve to obtain the moxidectin solid dispersion; (2) Premixing the solid dispersion obtained in the step (1) with microcrystalline cellulose serving as a first filler for 10-20 minutes, adding lactose serving as a second filler, and mixing for 10-20 minutes, wherein the mass ratio of the microcrystalline cellulose to the lactose is (1.0-1.5) 3.0; (3) Sequentially adding sieved fluorine Lei Lana and thiopyrimidine into the material in the step (2) and uniformly mixing; (4) Finally adding a disintegrating agent, a lubricant, and optionally an antioxidant and a flavoring agent, and mixing for 5-15 minutes; (5) And tabletting by adopting a pre-compression and main compression two-stage tabletting process to obtain the compound Florarana chewable tablet.
  9. 9. The method according to claim 8, wherein the pre-compression pressure is 4-6 kn and the main pressure is 12-18 kn during the tabletting.

Description

Compound Florana chewable tablet and preparation method thereof Technical Field The invention relates to the technical field of veterinary medicine preparations, in particular to a compound fluororalrana chewable tablet and a preparation method thereof. Background Parasite infections for dogs are ubiquitous worldwide, common ectoparasites such as fleas and ticks can cause itching and anemia in dogs and can transmit various insect-borne diseases, gastrointestinal nematodes such as roundworms and hookworms can cause digestive disorders and malnutrition, and blood parasites such as heartworms can cause serious damage to the cardiopulmonary system. For the control of canine parasites, most of the existing pharmaceutical preparations on the market are single or double pharmaceutical combinations, the control spectrum is limited, and the parasites of different types can be covered by combining multiple preparations, so that the administration is complex and the compliance is poor. In the aspect of preparation process, moxidectin has extremely low dosage, and the problems of uneven content distribution and large batch-to-batch difference easily occur when a conventional powder direct mixing method is adopted, so that the safety and stability of the preparation are affected. Although research is carried out on improving the dispersion and dissolution of hydrophobic drugs by using different types of auxiliary material systems, for extremely low-dose drugs, the existing systems still have the problems of large content fluctuation, easy degradation or crystallization aggregation during storage and the like, and no stable and reliable solution is formed yet. Therefore, how to achieve broad-spectrum control of various parasites in a single dosage form, and effectively solve the bottleneck problems of uniform distribution and insufficient stability of low-dose active ingredients, is still a technical problem to be solved in the field. Disclosure of Invention The invention aims to overcome the problems in the prior art and provide a compound Florana chewable tablet and a preparation method thereof, wherein by scientifically combining fluo Lei Lana, moxidectin and thiopyrimidine in a single tablet and adding a specific water-soluble carrier and a surfactant system, the broad-spectrum control of various parasites in and out of dogs is realized, and breakthrough progress is made in the aspects of uniform distribution of low-dose components, preparation stability and dog compliance. In order to achieve the aim, the first aspect of the invention provides a compound fluororalrana chewable tablet, which comprises, by weight, 25-600 parts of fluorine Lei Lana, 12.5-300 parts of thiopyrimidine, 5-350 parts of moxidectin solid dispersion, 40-300 parts of filler, 0.5-25 parts of disintegrating agent, 1-50 parts of lubricant, 0.2-2 parts of optional antioxidant and 1-50 parts of flavoring agent; The moxidectin solid dispersion is prepared by mixing moxidectin and poloxamer 407 and in the presence of sodium dodecyl sulfate and/or sodium dodecyl sulfate, and the particle size of the solid dispersion D 50 is 20-80 mu m. By adopting the technical scheme, the invention provides a unique solid dispersion design aiming at the adverse characteristics of low dosage, low solubility and easy crystallization of moxidectin in the compound insect repellent tablet. Moxidectin is not directly mixed into the tablet, but is first formed into a solid dispersion under the action of poloxamer 407 and sodium dodecyl sulfate and/or sodium dodecyl sulfonate, thereby achieving highly uniform distribution at very low dosage. The solid dispersion can stably keep the moxidectin in an amorphous or metastable state dispersion state, the solubility and the dissolution rate of the moxidectin are obviously improved in a compound system, and meanwhile, the crystallization induction when the moxidectin coexists with fluorine Lei Lana, thiopyrimidine and the like is avoided. Further, the particle size of the solid dispersion is strictly controlled within a window with the D 50 of 20-80 mu m, so that the obtained powder has good fluidity and compressibility, and structural stability is maintained in long-term storage, and the finished tablet is ensured to have excellent process adaptability and stability. On the basis, fluorine Lei Lana is used as an active ingredient for long-acting flea and tick killing, thiopyrimidine is used as a nematicide, the synergistic effect of the epothilone and the moxidectin treated by the solid dispersion is realized in the same tablet, the broad-spectrum coverage of internal and external parasites is ensured, the content uniformity of low-dose medicines and the forming strength of the tablet are both considered by the internal and external layering mode of microcrystalline cellulose and lactose, the rapid disintegration and release of the tablet in the oral cavity and the digestive tract environment are ensured by the introduction of the