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CN-121971394-A - Celecoxib preparation and preparation method thereof

CN121971394ACN 121971394 ACN121971394 ACN 121971394ACN-121971394-A

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and discloses a celecoxib tablet and a preparation method thereof, the celecoxib tablet consists of celecoxib, lactose microcrystalline cellulose compounded in a specific proportion, crospovidone-carboxymethyl starch sodium, a lubricant and a solubilization stabilizer, wherein the solubilization stabilizer is beta-cyclodextrin, sodium stearoyl lactate and meglumine. The preparation method comprises the steps of pretreatment of celecoxib and a solubilization stabilizer, granulating, drying and granulating in steps, and total mixed tabletting. According to the preparation method, the prepared celecoxib tablet is obviously improved in content uniformity, dissolution performance and storage stability by combining the synergistic effect of the compound solubilization stabilizer and the wet grinding process and a preparation method of stepwise mixing granulation, and the preparation process is simple and easy to operate, and is suitable for industrial mass production.

Inventors

  • YE FENG
  • ZHAO YUNLONG
  • XIE GUOYAN

Assignees

  • 山东新时代药业有限公司

Dates

Publication Date
20260505
Application Date
20260312

Claims (10)

  1. 1. The celecoxib tablet is characterized by comprising, by weight, 10-40 parts of celecoxib, 30-60 parts of lactose-microcrystalline cellulose compounded by 1:2, 5-15 parts of crospovidone-carboxymethyl starch sodium compounded by 1:1, 0.5-2 parts of lubricant and 0.3-1.2 parts of solubilization stabilizer.
  2. 2. Celecoxib tablet according to claim 1, wherein the solubilising stabilizer is cyclodextrin, sodium stearoyl lactylate, meglumine.
  3. 3. Celecoxib tablet according to claim 2, wherein the cyclodextrin is beta-cyclodextrin.
  4. 4. Celecoxib tablet according to claim 2, wherein the mass ratio of cyclodextrin, sodium stearoyl lactylate and meglumine is 1:1:1.
  5. 5. Celecoxib tablet according to claim 1, wherein the lubricant is selected from at least one of talcum powder, micro silica gel and magnesium stearate.
  6. 6. The celecoxib tablet according to claim 1, wherein the solubilization stabilizer and celecoxib are treated by weighing celecoxib, adding the celecoxib into an aqueous solution of beta-cyclodextrin, grinding the beta-cyclodextrin by a wet method to form a suspension, adding sodium stearoyl lactate and meglumine, and stirring and mixing the mixture.
  7. 7. The celecoxib tablet according to claim 6, wherein the beta-cyclodextrin aqueous solution is beta-cyclodextrin dissolved in water at 30-40 ℃.
  8. 8. Celecoxib tablet according to claim 7, wherein the water is used in an amount of 10-15 times the mass of beta-cyclodextrin.
  9. 9. Celecoxib tablet according to claim 6, wherein the wet grinding speed is 2000-3000 r/min for 10-30 minutes.
  10. 10. A method of preparing the celecoxib tablet of claim 1, wherein the method comprises the steps of: (1) Weighing celecoxib, adding the celecoxib into beta-cyclodextrin aqueous solution, performing wet grinding to form suspension, adding sodium stearoyl lactate and meglumine, and stirring and mixing; (2) Adding 70% -80% of 1:2 compound lactose-microcrystalline cellulose, stirring, mixing, granulating, drying and granulating; (3) Adding the rest 1:2 compound lactose-microcrystalline cellulose and 1:1 compound crospovidone-carboxymethyl starch sodium, mixing, adding lubricant, mixing, and tabletting.

Description

Celecoxib preparation and preparation method thereof Technical Field The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a celecoxib preparation and a preparation method thereof. Background The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art. Celecoxib (Celecoxib) is chemically named as 4- [5- (4-methylphenyl) -3- (trifluoromethyl) -1H-pyrazol-1-yl ] benzenesulfonamide, and the unique action mechanism of Celecoxib can specifically inhibit COX-2 activity and reduce the synthesis of inflammatory prostanoids, so that remarkable anti-inflammatory, analgesic and antipyretic effects are exerted, and meanwhile, serious gastrointestinal adverse reactions (such as bleeding, ulcer, perforation and the like) caused by the simultaneous inhibition of COX-1 by traditional NSAIDs are avoided, so that the Celecoxib has important clinical application value in the treatment of inflammatory diseases such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute pain. However, celecoxib belongs to a Biopharmaceutical Classification System (BCS) class II drug, and has the characteristics of high permeability and low solubility, which makes the celecoxib face a plurality of technical challenges in the preparation development process. 1. The problems of solubility and bioavailability are that the raw medicines are hardly dissolved in water, the oral absorption is slow, the bioavailability is low, the individual difference is large, the peak time is about 3 hours, and the rapid exertion of clinical curative effect is influenced. 2. The physical characteristics are difficult to solve, the texture is light, the bulk density is low, the aggregation is easy, the dissolution performance of the powder is difficult to effectively improve, the micronization has high requirements on equipment, the energy consumption is high, and the production cost is increased. 3. The preparation is difficult to process, viscous long needle-shaped crystals are easy to form in the tabletting process, are melted into hard blocks, and are easy to agglomerate into blocks when mixed with auxiliary materials, so that the mixing uniformity is poor, and the quality uniformity of the preparation is affected. 4. Stability challenges are that the preparation is easy to degrade under high-temperature and high-humidity conditions, and the shelf life and storage stability of the preparation are affected. In order to solve the problems, a person skilled in the art adds a surfactant or a cosolvent into a preparation, and Chinese patent publication No. CN113413371A discloses a celecoxib capsule and a preparation method thereof, wherein the celecoxib capsule comprises 25-80 parts of celecoxib, 19-72 parts of blank pill cores, 0.5-2 parts of wetting agent and 0.2-1 part of absorption accelerator, and the celecoxib capsule has good dissolution effect, easy absorption and high bioavailability by taking a novel surfactant as the wetting agent and mannitol or/and sorbitol as the absorption accelerator. The Chinese patent with publication number of CN102920676A discloses a celecoxib chewable tablet and a preparation method thereof, wherein the celecoxib chewable tablet comprises, by weight, 5-30% of celecoxib, 5-20% of a disintegrating agent, 20-80% of a filler, 5-30% of an adhesive, 0.5-5% of a glidant and 0.5-3% of a surfactant, and the surfactant is sodium dodecyl sulfate or tween-80. In the prior art, the wettability and the solubility of the medicine are often improved by adding surfactants such as Sodium Dodecyl Sulfate (SDS), tween 80 and the like or cosolvents such as ethanol, propylene glycol and the like. However, ① surfactants may cause irritation of the mucosa, ② co-solvents are limited in amount and may affect drug stability, and ③ may cause toxicity accumulation over time. Therefore, aiming at the potential safety hazard caused by the large usage amount of the surfactant in the existing celecoxib preparation and the technical bottleneck that the dissolution performance and the storage stability are difficult to be simultaneously considered, the celecoxib preparation which has low surface active dose, can effectively improve the hydrophobicity of celecoxib, accelerate the dissolution rate, has simple preparation process and excellent storage stability is developed, and becomes the technical problem to be solved in the current field urgently, and is the research starting point and the core target of the invention. Disclosure of Invention The invention aims to overcome the technical bottlenecks that the potential safety hazard, dissolution performance and storage stability are difficult to consider due to the large usage amount of surfactant in the