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CN-122005481-A - Tofacitinib citrate osmotic pump sustained release tablet and preparation method thereof

CN122005481ACN 122005481 ACN122005481 ACN 122005481ACN-122005481-A

Abstract

The invention discloses a tofacitinib citrate osmotic pump sustained-release tablet which comprises a tofacitinib citrate tablet core and a sustained-release coating layer coated on the surface of the tofacitinib citrate tablet core, wherein the tofacitinib citrate tablet core contains a waxy framework material, the sustained-release coating layer contains a sustained-release film material and a pore-forming agent, the sustained-release film material consists of Eudragit RL and Eudragit RS, and the pore-forming agent is a water-soluble pore-forming agent. The invention also discloses a preparation method of the tofacitinib citrate osmotic pump sustained-release tablet, which comprises the following steps of taking each component of a tablet core, uniformly mixing, tabletting to obtain the tablet core, coating the tablet core, and carrying out heat preservation and solidification to obtain the tofacitinib citrate osmotic pump sustained-release tablet. According to the invention, the corrosion controlled release and slow release coating layers of the waxy framework material are hierarchically coupled, so that the drug release stability is obviously improved, the tolerance to the change of the gastrointestinal physiological environment is stronger, and the drug is free from a reduction trend in long-term storage and dissolution.

Inventors

  • WANG HONG
  • WU ZONGHAO
  • ZHANG LIANGLIANG
  • ZHANG XIAOMAN
  • YANG XIANLONG
  • ZHANG CHAO
  • WANG JUN
  • SHENG YAOYAO

Assignees

  • 合肥华方医药科技有限公司

Dates

Publication Date
20260512
Application Date
20260416

Claims (10)

  1. 1. The tofacitinib citrate osmotic pump sustained-release tablet is characterized by comprising a tofacitinib citrate tablet core and a sustained-release coating layer coated on the surface of the tofacitinib citrate tablet core, wherein the tofacitinib citrate tablet core contains a waxy framework material, and the sustained-release coating layer contains a sustained-release membrane material and a pore-foaming agent; The wax skeleton material is at least one of hydrogenated vegetable oil, glyceryl stearate and glyceryl behenate, the slow-release film material consists of Eudragit RL and Eudragit RS, and the pore-forming agent is water-soluble pore-forming agent.
  2. 2. The tofacitinib citrate osmotic pump sustained-release tablet according to claim 1, wherein the weight ratio of the eudragit RL to the eudragit RS is 1:0.7-1.5.
  3. 3. The tofacitinib citrate osmotic pump sustained-release tablet according to claim 1 or 2, wherein the pore-forming agent is at least one of triethyl citrate, polyethylene glycol and glycerol.
  4. 4. The tofacitinib citrate osmotic pump sustained-release tablet according to claim 1 or 2, wherein the sustained-release coating layer accounts for 8-12wt% of the tablet core weight.
  5. 5. The tofacitinib citrate osmotic pump sustained-release tablet according to claim 1 or 2, wherein the dosage of the pore-forming agent is 5-10wt% of the weight of the sustained-release membrane material.
  6. 6. The tofacitinib citrate osmotic pump sustained-release tablet according to claim 1 or 2, wherein the content of waxy framework material in the tofacitinib citrate tablet core is 25-35wt%, and the content of tofacitinib is 5-6wt%.
  7. 7. The tofacitinib citrate osmotic pump sustained-release tablet according to claim 1 or 2, wherein the tofacitinib citrate tablet core further comprises one or more of a filler and a lubricant.
  8. 8. A method for preparing a tofacitinib citrate osmotic pump sustained-release tablet according to any one of claims 1 to 7, which is characterized by comprising the steps of taking each component of a tablet core, uniformly mixing, tabletting to obtain the tablet core, coating the tablet core, and carrying out heat preservation and solidification to obtain the tofacitinib citrate osmotic pump sustained-release tablet.
  9. 9. The method for preparing the tofacitinib citrate osmotic pump sustained-release tablet according to claim 8, wherein the coating condition is that the air inlet temperature is 50-60 ℃, the air outlet temperature is 25-35 ℃ and the atomization pressure is 0.05-0.1MPa.
  10. 10. The method for preparing a tofacitinib citrate osmotic pump sustained release tablet according to claim 8, wherein the tablet is cured at 30-50 ℃ for 20-28h.

Description

Tofacitinib citrate osmotic pump sustained release tablet and preparation method thereof Technical Field The invention relates to the technical field of pharmaceutical preparations, in particular to a tofacitinib citrate osmotic pump sustained release tablet and a preparation method thereof. Background Tofacitinib citrate is a Janus kinase (JAK) inhibitor developed by the company pyroxene. JAK belongs to intracellular enzymes, and can conduct signals generated by cytokine or growth factor-receptor interactions on cell membranes, thereby affecting the hematopoietic process and cellular immune function of cells, and in the signal transduction pathway, JAK phosphorylates and activates signal transduction factors and transcription activator (STAT), thereby regulating intracellular activities including gene expression. Tofacitinib citrate plays a therapeutic role by regulating a JAK signal transduction pathway and preventing STAT phosphorylation and activation, and is mainly used for treating rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis and the like at present. The tofacitinib citrate is a quick-release dosage form firstly marketed, an adult patient needs to take the medicine twice a day, the patient compliance is poor, a slow-release preparation for once a day is developed by using a gabion preparation subsequently, the original tofacitinib citrate slow-release tablet XR consists of a tablet core, a semipermeable membrane slow-release coating and a gastric-soluble film coating, a sample is a pink oval film coating, the coating is removed and then appears white or white-like, a medicine-containing coating film at the top end of the side surface of the oval tablet is provided with a small hole for releasing medicine by using a laser means, the punching position of a punching machine is extremely high in control precision requirement, the production efficiency is lower, the production cost is high, the dissolution behavior is greatly influenced by the fluctuation of pH value, auxiliary materials such as methanol, acetone and the like which harm the body even cause blindness in the production process are used, the process is complex, the production equipment is expensive, the requirement on the precision of equipment is high, the operation is inconvenient, and the production period is long. Meanwhile, some related researches are improved, but the problems are different, for example, in a patent CN105101952B, 60-85% of sorbitol is mainly used as a tablet core permeation source, a semipermeable membrane coating mainly comprises cellulose acetate and hydroxypropyl cellulose in a weight ratio of 6:4, the hygroscopicity of sorbitol is extremely strong, the environmental humidity is required to be strictly controlled in the production process, the non-hygroscopicity in the mixed tabletting process is ensured, in addition, the semipermeable membrane coating adopts a larger proportion of hydroxypropyl cellulose as a pore-forming agent, so that polar solvent methanol is required for dissolution and then coating, a toxic reagent which is easy to cause blindness is introduced, potential safety hazards are brought, the dissolution data range under the patent is wider, the release behavior cannot be controlled better accurately, and the dissolution speed of the preparation is reduced after long-term storage. The patent CN 112587492A discloses a membrane-controlled and skeleton-dual slow-release tofacitinib citrate slow-release tablet, which is prepared by the steps of (1) sieving tofacitinib citrate raw materials, waxy skeleton materials, filling agents, lubricants and the like respectively, wherein the sieving number is 20-30 meshes, mixing by using a mixer after sieving to obtain mixed powder for tabletting, (2) taking out the mixed powder (1), pressing the mixed powder into tablets by using a tablet press, and (3) taking out the tofacitinib citrate tablet obtained in the step (2), and wrapping a slow-release coating material on a drug tablet core by coating equipment to obtain the final slow-release coated tablet. The waxy skeleton material may be one or several of hydrogenated vegetable oil, glyceryl stearate and glyceryl behenate, and the slow release coating material may be one or several of ethyl cellulose, cellulose acetate and cellulose water dispersion. However, the research shows that the dissolution behavior is greatly fluctuated by the pH value, and the stable dissolution behavior can not be maintained in different pH environments. Therefore, there is a need to develop a slow release preparation of tofacitinib citrate which can avoid using toxic solvents such as methanol, has high process safety, simultaneously fundamentally overcomes the problem of long-term storage stability caused by strong hygroscopicity, can accurately regulate and control the drug release behavior, and keeps stable dissolution in different pH environments. Disclosure of Invention Based on the technical