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CN-122005474-A - Doxepin hydrochloride tablet and preparation method thereof

CN122005474ACN 122005474 ACN122005474 ACN 122005474ACN-122005474-A

Abstract

The invention discloses a doxepin hydrochloride tablet and a preparation method thereof, belonging to the field of pharmaceutical preparations. The tablet comprises 1-10 parts of doxepin hydrochloride, 60-90 parts of filler, 3-12 parts of disintegrating agent, 1-8 parts of adhesive, 0.5-3 parts of glidant and 0.5-3 parts of lubricant, wherein doxepin hydrochloride is a bulk drug subjected to micronization treatment, the D90 particle size is less than or equal to 15 mu m, and the disintegrating agent is a compound of crospovidone and carboxymethyl starch sodium according to a weight ratio of 1:0.5-2. The preparation method comprises micronizing doxepin hydrochloride, mixing the main medicine and adjuvant with equal amount by progressive mixing method, and tabletting. The invention solves the problem of poor content uniformity of low-dosage tablets by combining micronization treatment with equivalent progressive mixing process, realizes rapid disintegration by a composite disintegrating agent system, avoids wet heat treatment by a direct tabletting process, and improves the stability of the preparation. The tablet prepared by the invention has the advantages of good content uniformity, rapid disintegration, excellent stability, simple process and suitability for industrial production.

Inventors

  • YANG YINGJIN
  • YANG YINGDONG
  • LU HONGBIN
  • FAN CHAO
  • YANG LEI

Assignees

  • 苏州弘森药业股份有限公司

Dates

Publication Date
20260512
Application Date
20260331

Claims (10)

  1. 1. Doxepin hydrochloride tablet, characterized in that the tablet comprises the following components in parts by weight: 1-10 parts of doxepin hydrochloride, 60-90 Parts of filler, 3-12 Parts of disintegrating agent, 1-8 Parts of an adhesive, wherein the adhesive comprises, 0.5-3 Parts of glidant, 0.5-3 Parts of lubricant; Wherein doxepin hydrochloride is a bulk drug after micronization treatment, and the D90 particle size is less than or equal to 15 mu m.
  2. 2. Doxepin hydrochloride tablet according to claim 1 wherein said doxepin hydrochloride is used in an amount of 3-6 parts by weight.
  3. 3. Doxepin hydrochloride tablet according to claim 1 wherein said disintegrant is a complex of crospovidone and sodium carboxymethyl starch in a weight ratio of 1:0.5-2.
  4. 4. Doxepin hydrochloride tablet according to claim 1 wherein said filler is selected from one or more of microcrystalline cellulose, lactose, mannitol, said binder is selected from one or more of hypromellose, povidone, hyprolose, said glidant is selected from one or more of silica, talc, and said lubricant is selected from one or more of magnesium stearate, sodium stearyl fumarate.
  5. 5. Doxepin hydrochloride tablet according to claim 1 wherein said binder is hypromellose, said glidant is silicon dioxide and said lubricant is magnesium stearate.
  6. 6. Doxepin hydrochloride tablet according to claim 1 further comprising a film coating layer, wherein the weight of the film coating layer is 2% -4% of the weight of the tablet core.
  7. 7. A process for the preparation of doxepin hydrochloride tablets as claimed in any one of claims 1 to 6 comprising the steps of: (1) Micronizing doxepin hydrochloride, and controlling the D90 particle diameter to be less than or equal to 15 μm; (2) Uniformly mixing the micronized doxepin hydrochloride with the filler, the disintegrating agent and the adhesive by adopting an equivalent progressive mixing method, specifically, firstly mixing the micronized doxepin hydrochloride with the equivalent filler for 5-10 minutes, then adding the rest filler, the disintegrating agent and the adhesive for 10-20 minutes, and finally adding the glidant and the lubricant for 3-8 minutes to obtain a total mixed material; (3) Directly tabletting the total mixed material, controlling the tabletting pressure to be 5-15kN, and obtaining tablet cores; (4) Optionally, film coating the tablet core to obtain doxepin hydrochloride tablet.
  8. 8. The process according to claim 7, wherein the micronizing treatment in step (1) is carried out by using a jet mill at a pulverizing pressure of 0.6 to 1.0MPa and a feeding rate of 5 to 15kg/h.
  9. 9. The process according to claim 7, wherein the tablet core obtained in the step (3) has a hardness of 40 to 80N and a disintegration time of 5 minutes or less.
  10. 10. The process of claim 7, wherein the direct compression in step (3) is performed without adding any wetting agent or binder solution.

Description

Doxepin hydrochloride tablet and preparation method thereof Technical Field The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a doxepin hydrochloride tablet and a preparation method thereof. Background Doxepin hydrochloride (Doxepin Hydrochloride) is a tricyclic antidepressant, and the action mechanism of doxepin hydrochloride is mainly to inhibit reuptake of 5-hydroxytryptamine and norepinephrine by the central nervous system, so that the concentration of the two neurotransmitters in synaptic cleft is increased, and the antidepressant, anxiolytic and sedative effects are exerted. Clinically, doxepin hydrochloride common tablets (25 mg, 50mg and other specifications) are widely used for treating depression and anxiety neurosis. In recent years, low doses of doxepin hydrochloride (3 mg, 6 mg) have been demonstrated to be useful in the treatment of insomnia characterized by difficulty in sleep maintenance, because it mainly exerts histamine H1 receptor antagonism at low doses, producing sedative hypnotic effects, while the side effects of anticholinergic etc. are significantly reduced, and have become an important choice for insomnia treatment. Currently, the common oral dosage form of doxepin hydrochloride is mainly a common tablet. However, the existing common tablets still have the following technical problems in actual production and application, namely firstly, for low-dose specifications (3 mg and 6 mg), the proportion of main drugs to the tablet is extremely low (usually lower than 5%), the main drugs are unevenly distributed easily due to the adoption of a conventional mixing process, so that the content difference among the tablets is large, the clinical curative effect and the medication safety are influenced, the key technical problems commonly faced by low-dose preparations are solved, secondly, the doxepin hydrochloride raw material has certain hygroscopicity, the color change and the impurity increase are easy to occur under the damp-heat condition, the higher requirements are put on the stability of the preparation, and furthermore, the disintegration performance of the existing tablets is required to be optimized, and for insomnia patients needing quick effect, the drug absorption speed and the sleeping time are influenced due to slow disintegration. In the prior art, doxepin hydrochloride tablets and a preparation method thereof have been reported. Prior art 1 (CN 121177231A) discloses a doxepin hydrochloride tablet and a preparation method thereof. Aiming at the problems of high wettability, unstable damp and heat and easy occurrence of sticking and flushing of doxepin hydrochloride, the technical scheme adopts a method for preparing solid dispersion from doxepin hydrochloride and polyethylene glycol 6000 (the weight ratio of the medicine to the carrier is 1:4-1:8), so that the medicine is highly dispersed in a carrier material in the states of molecules, colloid, amorphous and the like, the wrapping effect is realized, and the solid dispersion is directly tabletted after being mixed with a filling agent, a disintegrating agent, a glidant and a lubricant. The technology effectively improves the problems of wettability and stability of the medicine by a solid dispersion technology, and simplifies the production flow by adopting a direct tabletting process. However, the technical scheme has the following defects that firstly, the preparation process of the solid dispersion involves heating and melting (the melting temperature of polyethylene glycol 6000 is about 60 ℃) and rapid cooling steps, the medicine dispersion can be realized, but the potential thermal degradation risk exists in the melting treatment, the process is relatively complex, the energy consumption is high, secondly, the technology does not specially optimize the content uniformity problem of low-dose specifications (3 mg and 6 mg), the mixing process is conventional mixing, the special mixing modes such as equal increment and the like are not adopted, the content uniformity of the low-dose preparation with the extremely low main medicine ratio is difficult to be fully ensured, thirdly, the disintegrating agent disclosed by the technology is only conventional selection, and the specific disintegrating agent combination and the synergistic effect are not involved. Prior art 2 (CN 108096363A) discloses a doxepin hydrochloride tablet and a preparation method thereof. The technical scheme aims to reduce the side effects of doxepin hydrochloride tablets, and the doxepin hydrochloride and the shizandra berry extract are compounded to prepare tablets, so that the synergistic effect of the shizandra berry extract is utilized to reduce the side effects of doxepin hydrochloride such as hyperhidrosis, dry mouth, dizziness and the like, and simultaneously improve the treatment effect. The technology adopts a wet granulation process, takes starch, dextrin or ethyl cellulose as a binder