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CN-122005477-A - Trazodone hydrochloride sustained release tablet and preparation method thereof

CN122005477ACN 122005477 ACN122005477 ACN 122005477ACN-122005477-A

Abstract

The sustained release tablet uses high-viscosity hypromellose and low-viscosity hypromellose in combination as sustained release materials, can play a synergistic effect to form a double-skeleton structure, enables the medicine to be released stably and uniformly within 12-24 hours, can accurately regulate and control the medicine release speed, reduces blood concentration fluctuation, reduces medicine taking times to one day, reduces adverse reaction risks such as dizziness and somnolence, improves the curative effect, compliance and safety of patients, and meanwhile, has consistent release behaviors in different pH media, good in vivo absorption predictability, slow related substance growth, good tablet stability, simple preparation method and low cost, and is suitable for industrial production.

Inventors

  • WANG TIAN
  • ZHOU DONGYAN
  • XIN NI

Assignees

  • 南京海纳制药有限公司
  • 南京海纳医药科技股份有限公司
  • 南京海纳药物研究有限公司
  • 南京泛海医药科技有限公司

Dates

Publication Date
20260512
Application Date
20260402

Claims (10)

  1. 1. A trazodone hydrochloride sustained release tablet is characterized by comprising, by weight, 140-160 parts of trazodone hydrochloride, 100-140 parts of a sustained release material, 50-70 parts of a filler, 3-8 parts of an adhesive, 1-5 parts of a lubricant and 1-5 parts of a glidant, wherein the filler is one or more of microcrystalline cellulose, lactose or pregelatinized starch, the sustained release material is high-viscosity hypromellose and low-viscosity hypromellose, the mass ratio of the high-viscosity hypromellose to the low-viscosity hypromellose is 0.25-4:1, the adhesive is povidone K30 or hypromellose, the lubricant is magnesium stearate, and the glidant is colloidal silicon dioxide.
  2. 2. The sustained release tablet of claim 1, wherein the filler is microcrystalline cellulose, the binder is povidone K30, the high viscosity hypromellose has a viscosity in the range of 10,000 to 100,000 mPa-s, preferably the high viscosity hypromellose is HPMC K100M, HPMC K15M or HPMC K10M, the low viscosity hypromellose has a viscosity in the range of 3 to 15 mPa s, preferably the low viscosity hypromellose is E3 LV, E5 LV or E15LV.
  3. 3. The sustained release tablet of claim 2, wherein the sustained release tablet is prepared from the following components, by weight, 145-155 parts of trazodone hydrochloride, 110-130 parts of sustained release material, 55-65 parts of microcrystalline cellulose, 30-6 parts of povidone K, 2-4 parts of magnesium stearate and 1.5-2.5 parts of colloidal silicon dioxide.
  4. 4. The sustained release tablet of claim 3, wherein the sustained release tablet is prepared from the following components, by weight, 150 parts of trazodone hydrochloride, 115-125 parts of a sustained release material, 60 parts of microcrystalline cellulose, 30 parts of povidone K, 3 parts of magnesium stearate and 2 parts of colloidal silicon dioxide, wherein the mass ratio of high-viscosity hypromellose to low-viscosity hypromellose in the sustained release material is 0.3-3:1, the high-viscosity hypromellose is HPMC K100M or HPMC K10M, and the low-viscosity hypromellose is E3 LV or E5 LV.
  5. 5. The sustained release tablet of claim 4, wherein the sustained release tablet is prepared from the following components, by weight, 150 parts of trazodone hydrochloride, 120 parts of a sustained release material, 60 parts of microcrystalline cellulose, 30 parts of povidone K, 3 parts of magnesium stearate and 2 parts of colloidal silicon dioxide, wherein the sustained release material is HPMC K100M and E5 LV, and the mass ratio of HPMC K100M to E5 LV is 0.3-3:1.
  6. 6. The trazodone hydrochloride sustained release tablet according to claim 5, wherein the sustained release tablet is prepared from the following components in parts by weight: 150 parts of trazodone hydrochloride, 100M 30 parts of HPMC K, E5 LV 90 parts, 60 parts of microcrystalline cellulose, 30 parts of povidone K, 3 parts of magnesium stearate and 2 parts of colloidal silicon dioxide; 150 parts of trazodone hydrochloride, 100M 80 parts of HPMC K, 40 parts of E5 LV, 60 parts of microcrystalline cellulose, 30 parts of povidone K, 3 parts of magnesium stearate and 2 parts of colloidal silicon dioxide; 150 parts of trazodone hydrochloride, 100M 90 parts of HPMC K, 30 parts of E5 LV, 60 parts of microcrystalline cellulose, 30 parts of povidone K, 3 parts of magnesium stearate and 2 parts of colloidal silicon dioxide.
  7. 7. The sustained-release tablet of claim 4, wherein the sustained-release tablet is prepared from the following components, by weight, 150 parts of trazodone hydrochloride, 120 parts of a sustained-release material, 60 parts of microcrystalline cellulose, 30 parts of povidone K, 3 parts of magnesium stearate and 2 parts of colloidal silicon dioxide, wherein the sustained-release material is HPMC K10M and E3 LV, the mass ratio of the HPMC K10M to the E3 LV is 0.3-3:1, and preferably the sustained-release tablet is prepared from the following components, by weight, 150 parts of trazodone hydrochloride, 80 parts of HPMC K10M, 40 parts of E3 LV, 40 parts of microcrystalline cellulose, 30 parts of povidone K, 3 parts of magnesium stearate and 2 parts of colloidal silicon dioxide.
  8. 8. The preparation method of the trazodone hydrochloride sustained release tablet according to claim 1, which is characterized by comprising the following steps: (1) Pre-treating, sieving trazodone hydrochloride, low viscosity hypromellose and filler for use; (2) Preparing an adhesive solution by dissolving an adhesive in an ethanol aqueous solution; (3) Granulating, mixing and tabletting, namely uniformly mixing the trazodone hydrochloride, the low-viscosity hypromellose and the filler which are sieved in the step (1), adding the binder solution in the step (2) for wet granulation, drying, granulating, mixing the obtained granules with magnesium stearate, the high-viscosity hypromellose and colloidal silicon dioxide, tabletting, and preparing the sustained release tablet.
  9. 9. The preparation method of the trazodone hydrochloride sustained-release tablet according to claim 8, wherein the filler is microcrystalline cellulose, the binder is povidone K30, the viscosity of the high-viscosity hypromellose is in the range of 10,000-100,000 mPa-s, preferably the high-viscosity hypromellose is HPMC K100M, HPMC K15M or HPMC K10M, the viscosity of the low-viscosity hypromellose is in the range of 3-15 mPa-s, preferably the low-viscosity hypromellose is E3 LV, E5 LV or E15LV.
  10. 10. The preparation method of the trazodone hydrochloride sustained release tablet according to claim 9, wherein, In step (1), sieving with 60-100 mesh sieve, preferably 80 mesh; In the step (2), the volume ratio of the ethanol in the ethanol water solution is 40-60%, preferably 50%, and the concentration of the povidone K30 in the adhesive solution is 3-8%, preferably 5%; In step (3), the drying temperature is 50-60 ℃ and the moisture content is lower than 2.0%, preferably 55 ℃ and the moisture content is lower than 1.5%.

Description

Trazodone hydrochloride sustained release tablet and preparation method thereof Technical Field The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a trazodone hydrochloride sustained release tablet and a preparation method thereof. Background Trazodone hydrochloride (Trazodone Hydrochloride) is an antidepressant of the triazolopyridine class, mainly used for the treatment of all kinds of depression and anxiety associated with the symptoms of depression. The mechanism of action is mainly to selectively inhibit reuptake of 5-hydroxytryptamine (5-HT) and antagonize 5-HT2 receptors. Currently, most commercially available trazodone hydrochloride preparations are common quick-release tablets. Patients need to take the medicine for 2-3 times every day, which is easy to cause great fluctuation of blood concentration and peak valley phenomenon. When the blood concentration is high (Cmax), the incidence of adverse reactions such as dizziness, somnolence, and postural hypotension may be increased, and when the blood concentration is low (trough concentration), the curative effect may be affected, resulting in poor control of symptoms. The slow release preparation technology can solve the problems. The medicine can be slowly and uniformly released in the body, and the stable blood concentration is maintained, so that the medicine taking times (usually once a day) are reduced, the compliance of patients is improved, the incidence rate of adverse reactions is reduced, and the continuous treatment effect is maintained. However, developing trazodone hydrochloride into a sustained release preparation faces a plurality of technical challenges (1) the solubility problem is that trazodone hydrochloride has higher solubility in water, and the difficulty of designing a prescription process for slowly releasing trazodone hydrochloride is higher. (2) Stability problems trazodone is sensitive to light, heat and humidity, and stability is considered in the preparation process. (3) Release behavior control-the release profile of the drug needs to be precisely controlled to be sustained in the gastrointestinal tract for about 12-24 hours to avoid dose dumping (Dose Dumping). (4) Individual difference, namely ensuring that the release behaviors of the sustained release tablets in gastrointestinal tract environments with different pH values are consistent, and reducing the influence of food and individual physiological differences. Patent CN 105748421a discloses a sustained-release tablet containing trazodone hydrochloride and a preparation method thereof, wherein high-viscosity HPMC is used as a framework material to control the release of the drug in combination with a water-soluble filler. The gel layer is thickened, the medicine diffusion path is lengthened, the release rate is naturally slowed down (the time curve gradient is reduced) along with the time of the single-layer framework structure, the later blood concentration is insufficient, and a certain improvement space exists. Patent CN 105748421a discloses a sustained-release preparation containing trazodone hydrochloride oral solution and a preparation method thereof, and adopts a resin polymer sustained-release material to control the release of the drug. Most of the resin polymer slow-release materials are diffused or released at the first stage, the rate is attenuated along with time, the later blood concentration is insufficient, the process aspect is relatively complex, and a certain improvement space exists. Disclosure of Invention The invention aims to provide a trazodone hydrochloride sustained-release tablet based on the prior art, which uses high-viscosity hypromellose and low-viscosity hypromellose as sustained-release materials to play a synergistic effect to form a double-skeleton structure, so that the medicine can be released stably and uniformly within 12-24 hours, the medicine release speed can be accurately regulated and controlled, the fluctuation of blood concentration is reduced, the medicine taking times are reduced to one time a day, the risks of adverse reactions such as dizziness and somnolence are reduced, the curative effect, compliance and safety of patients are improved, meanwhile, the release behavior of the sustained-release tablet in different pH media is consistent, the in-vivo absorption predictability is good, the related substances are slowly increased, the stability of the tablet is good, the preparation method is simple, the cost is low, and the sustained-release tablet is suitable for industrial production. The invention also aims to provide a preparation method of the trazodone hydrochloride sustained release tablet. The technical scheme of the invention is as follows: The sustained release tablet is prepared from (by weight parts) trazodone hydrochloride 140-160, sustained release material 100-140, filler 50-70, adhesive 3-8, lubricant 1-5, and glidant 1-5. In the invention, the fil