CN-122005471-A - Oseltamivir phosphate freeze-dried tablet and preparation method thereof

Abstract

The invention relates to oseltamivir phosphate freeze-dried tablets and a preparation method thereof. The oseltamivir phosphate freeze-dried tablet comprises oseltamivir phosphate as an active ingredient and water-soluble starch as a framework forming agent. The invention applies water-soluble starch to skeleton construction of oseltamivir phosphate freeze-dried tablet, wherein the water-soluble starch is derived from natural plants, has good biocompatibility and extremely high safety, the freeze-dried tablet can be rapidly disintegrated in an oral cavity within 5 seconds, the medicine taking compliance of a patient is improved, the water-soluble starch is odorless, the taste is natural and soft, meanwhile, a compact and porous structure formed in the preparation can wrap active ingredients to a certain extent to cover bitterness, thereby effectively improving the taste, the water-soluble starch has moderate and good viscosity, a three-dimensional net skeleton with uniform and firm pores is formed in the freeze-drying process, the freeze-dried tablet has good taste and mechanical strength, the freeze-dried tablet is convenient for the patient to take, and the water-soluble starch can be rapidly dissolved, so that the process flow is simpler, more convenient and more efficient, and is suitable for mass production.

Inventors

• ZHAO LEI
• Guo Limiao
• PAN TIECHENG
• ZHANG JIAN
• AN MINGYUE
• WANG SHAN
• XIU YONG
• CUI NANA
• LIANG QINGTAO
• WANG YUBIN

Assignees

• 北京星昊盈盛药业有限公司

Dates

Publication Date

20260512

Application Date

20260303

Claims (10)

1. 1. The oseltamivir phosphate freeze-dried tablet is characterized by comprising an active ingredient and a skeleton forming agent, wherein the active ingredient is oseltamivir phosphate, and the skeleton forming agent is water-soluble starch.
2. 2. Oseltamivir phosphate freeze-dried tablet according to claim 1, wherein the content of the skeleton-forming agent is 10% -40%.
3. 3. Oseltamivir phosphate freeze-dried tablet according to claim 1, wherein the water-soluble starch solubility is not less than 60g/100ml.
4. 4. The oseltamivir phosphate freeze-dried tablet of claim 1, further comprising a flavoring agent, wherein the flavoring agent comprises one or both of a sweetener and a flavor.
5. 5. The oseltamivir phosphate freeze-dried tablet of claim 4, wherein said sweetener comprises one or more of sucralose, aspartame, acesulfame potassium, saccharin sodium, steviol glycosides.
6. 6. The oseltamivir phosphate freeze-dried tablet of claim 4, wherein said flavour comprises one or more of orange flavour, grapefruit flavour, chocolate flavour, coffee flavour.
7. 7. The method for preparing oseltamivir phosphate freeze-dried tablets according to any one of claims 1 to 6, which is characterized by comprising the following steps: S1, dissolving or suspending oseltamivir phosphate, water-soluble starch and other auxiliary materials in purified water to form uniform liquid medicine; s2, quantitatively pouring the liquid medicine obtained in the step S1 into a mold plate; S3, placing the mold plate in an environment of-75 ℃ to-120 ℃ to quickly freeze the liquid medicine; s4, freeze-drying the quick-frozen liquid medicine to obtain oseltamivir phosphate freeze-dried tablets.
8. 8. The method for preparing oseltamivir phosphate freeze-dried tablet according to claim 7, wherein in step S1, the solid content of the liquid medicine is controlled to be 5% -30%.
9. 9. The method for preparing oseltamivir phosphate freeze-dried tablet according to claim 7, wherein in step S4, the freeze-drying step comprises: s41, pre-freezing, namely keeping at the temperature of-20 ℃ to-30 ℃ for 2-4 hours; s42, sublimation drying, namely keeping for 4-8 hours at the temperature of-10 ℃ to 10 ℃ and the vacuum degree of 20 Pa-50 Pa; s43, resolving and drying, namely keeping at 20-30 ℃ for 2-3 hours.
10. 10. The method for preparing oseltamivir phosphate freeze-dried tablet according to claim 7, further comprising the steps of: s5, laminating, cutting, printing batch numbers and production dates.

Description

Oseltamivir phosphate freeze-dried tablet and preparation method thereof Technical Field The invention relates to the technical field of pharmaceutical preparations, in particular to oseltamivir phosphate freeze-dried tablets and a preparation method thereof. Background Currently, influenza virus (abbreviated influenza virus) is an RNA virus that mainly infects human respiratory tract and causes influenza. For the elderly, infants, pregnant women, or people with chronic basic diseases and immunosuppression, influenza virus is easy to develop into serious symptoms after infection, and serious complications such as pneumonia, myocarditis, respiratory failure and the like can be caused, even death is caused. Oseltamivir (Oseltamivir) is a neuraminidase inhibitor which inhibits the neuraminidase activity of influenza virus and prevents release of newly formed viral particles from host cells, thereby interrupting the viral infection cycle and achieving the goal of treating influenza. Oseltamivir is an efficient antiviral drug with strong selectivity developed by reasonably designing drugs (Rational Drug Design) based on the three-dimensional structure of influenza neuraminidase. Oseltamivir phosphate is an important neuraminidase inhibitor, and is a first-line medicine for treating and preventing influenza A and B. Currently, the commercial oseltamivir phosphate preparation is mainly capsules and dry suspension (needing temporary formulation). For children, the elderly and dysphagia patients, there is difficulty in swallowing capsules. While the dry suspension solves the swallowing problem, the dry suspension needs to be brewed by water, is inconvenient to use in the situations of lack of clean water sources or traveling and the like, and the dosage accuracy is easily affected by the blending operation. The oral freeze-dried tablet is a dosage form which can be rapidly disintegrated or dissolved in the oral cavity without water, and perfectly solves the problems. The prior art oral freeze-dried tablets often use gelatin, mannitol, pullulan and the like as a skeleton. However, these materials have some disadvantages, such as the risk of animal-derived diseases and vegetarian limitation of gelatin, larger influence of temperature and pH, easier shrinkage and deformation of the structure after freeze-drying, loose and weaker structure after independent use of mannitol, inability to form a stable skeleton with certain strength, complex process and higher cost of pullulan polysaccharide produced by microbial fermentation, possible supply fluctuation, and the formed skeleton is generally compact, relatively slow in dissolution speed, slightly viscous in taste and easy to absorb moisture. Therefore, there is an urgent need in the art to develop a new technology for preparing oseltamivir phosphate oral freeze-dried tablets using safer, lower cost and more widely available framework materials. Disclosure of Invention The invention aims to provide oseltamivir phosphate freeze-dried tablets and a preparation method thereof, and the freeze-dried tablets have the advantages of rapid disintegration, good taste, simple preparation process, high safety and low cost. The invention provides oseltamivir phosphate freeze-dried tablets, which comprise an active ingredient and a skeleton forming agent, wherein the active ingredient is oseltamivir phosphate with a therapeutically effective dose, and the skeleton forming agent is water-soluble starch. Preferably, the content of the skeleton forming agent is 10% -40%. Preferably, the water-soluble starch source is commercially available and available from public sources (Jiake organism, lot number 20250102), meets the pharmaceutical grade standard, can be fully dissolved in cold water, and can reach or exceed 60g/100ml in water at normal temperature. Preferably, the flavoring agent also comprises a flavoring agent, wherein the flavoring agent comprises one or two of sweetener and essence. Preferably, the sweetener comprises one or more of sucralose, aspartame, acesulfame potassium, sodium saccharin, steviol glycosides. Preferably, the essence comprises one or more of orange essence, grapefruit essence, chocolate essence and coffee essence. In a second aspect of the invention, a preparation method of oseltamivir phosphate freeze-dried tablets is provided, comprising the following steps: S1, dissolving or suspending oseltamivir phosphate, water-soluble starch and other auxiliary materials in purified water to form uniform liquid medicine; s2, quantitatively pouring the liquid medicine obtained in the step S1 into a mold plate; S3, placing the mold plate in an environment of-75 ℃ to-120 ℃ to quickly freeze the liquid medicine; s4, freeze-drying the quick-frozen liquid medicine to obtain oseltamivir phosphate freeze-dried tablets. Preferably, in step S1, the solid content of the liquid medicine is controlled to be 5% -30%. Preferably, in step S4, the freeze-drying step includes: s41, pre-fr