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CN-121971398-A - Dapoxetine hydrochloride tablet pharmaceutical composition and preparation method thereof

CN121971398ACN 121971398 ACN121971398 ACN 121971398ACN-121971398-A

Abstract

The invention discloses a dapoxetine hydrochloride tablet pharmaceutical composition and a preparation method thereof, belonging to the technical field of pharmaceutical preparations. The composition comprises dapoxetine hydrochloride, sodium bicarbonate, a filler, a disintegrating agent and a lubricant. Aiming at the problems of low dissolution rate, poor stability, complex preparation process and the like of the dapoxetine hydrochloride tablet in the prior art, the preparation method optimizes the raw material pretreatment process by introducing sodium bicarbonate as a key auxiliary material, omits the traditional adhesive and obviously improves the dissolution rate and the preparation stability. The preparation method comprises pre-drying filler (microcrystalline cellulose) until water content is less than or equal to 2.0%, sieving sodium bicarbonate with 100 mesh sieve, mixing with dapoxetine hydrochloride and lubricant, tabletting, and coating. The method has the advantages of simple process and low cost, is suitable for industrial production, and the obtained tablet has high dissolution and excellent stability under high temperature, high humidity and illumination conditions.

Inventors

  • MA YUTING
  • ZHENG JIAO
  • XU KUN
  • Tu Qingkun
  • LI CHUNSHENG
  • GAO JUNXIA
  • ZHENG DAN
  • CHEN QI
  • WU YAN
  • FAN JING
  • CHEN YUN
  • WU JINGLIANG
  • GAO WEI
  • BAI MENGJIAO

Assignees

  • 天方药业有限公司

Dates

Publication Date
20260505
Application Date
20260109

Claims (10)

  1. 1. The dapoxetine hydrochloride tablet pharmaceutical composition is characterized by comprising a tablet core and a film coating, wherein the tablet core comprises, by weight, 10% -50% of dapoxetine hydrochloride, 0.5% -5% of sodium bicarbonate, 40% -70% of a filler, 0.5% -5% of a disintegrating agent and 0.5% -5% of a lubricant, the filler is selected from one or more of microcrystalline cellulose, cellulose-lactose and pregelatinized starch, the disintegrating agent is selected from one or more of dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crosslinked sodium carboxymethyl cellulose and crosslinked povidone, the lubricant is selected from one or more of magnesium stearate, silicon dioxide and talcum powder, and the film coating is 1.5% -3.5% of the weight of the tablet core.
  2. 2. The dapoxetine hydrochloride tablet pharmaceutical composition of claim 1, wherein the tablet core comprises, by weight, 20% -40% of dapoxetine hydrochloride, 1% -3% of sodium bicarbonate, 50% -70% of a filler, at least one of microcrystalline cellulose and cellulose-lactose, 0.5% -5% of a lubricant, magnesium stearate and 2.0% -3.0% of film coating weight gain.
  3. 3. The dapoxetine hydrochloride tablet pharmaceutical composition of claim 2, wherein the tablet core is composed of the following components, by weight, 30% of dapoxetine hydrochloride, 2% of sodium bicarbonate, 30% of microcrystalline cellulose, 33.5% of cellulose-lactose and 1.5% of magnesium stearate.
  4. 4. The dapoxetine hydrochloride tablet pharmaceutical composition of any of claims 1 to 3, wherein the dapoxetine hydrochloride has a particle size distribution of d90≤150 μm and a bulk density of 0.45 g/mL to 0.55g/mL.
  5. 5. A dapoxetine hydrochloride tablet pharmaceutical composition according to any of claims 1 to 3, wherein said sodium bicarbonate is sieved through a 100 mesh sieve with a screen residue of less than or equal to 5%.
  6. 6. The dapoxetine hydrochloride tablet pharmaceutical composition of claim 1, wherein the cellulose-lactose is a mixture of microcrystalline cellulose and lactose in a mass ratio of (2-4) to (6-8).
  7. 7. The dapoxetine hydrochloride tablet pharmaceutical composition of claim 2, wherein the film coat weight gain is 2.5% of the tablet core weight.
  8. 8. A process for the preparation of a pharmaceutical composition of dapoxetine hydrochloride tablet according to any of claims 1 to 7, comprising the steps of: (1) Pretreating, namely drying the filler until the moisture is less than or equal to 2.0%, and sieving sodium bicarbonate with a sieve of more than 100 meshes; (2) Mixing, namely placing the pretreated dapoxetine hydrochloride, the disintegrating agent, the sodium bicarbonate and the filler into an automatic lifting hopper mixer, and mixing for 30-60 minutes at 10-20 rpm to obtain mixed powder ①, wherein a screen with the aperture of 0.6-0.8 mm is arranged on a powder mixing ① by a crushing and granulating machine, the frequency of 6-8 Hz is set, magnesium stearate is added after sieving, and then the mixture is mixed in the automatic lifting hopper mixer at the mixing rotating speed of 10-15 rpm for 10-20 minutes; (3) Tabletting, namely directly tabletting the uniformly mixed powder, wherein the hardness of the tablet is controlled to be 5 kg-10 kg; (4) Coating, namely coating the tablet core.
  9. 9. The method according to claim 8, wherein a high-speed tablet press is used in the tabletting step, the diameter of a die is 8 mm-12 mm, and the tabletting pressure is 10 KN-20 KN.
  10. 10. The preparation method of the gastric-soluble film coating premix according to claim 8, wherein the preparation process of the coating liquid comprises the steps of adding the gastric-soluble film coating premix into purified water, stirring for 30-50 min, and preparing the film coating liquid with the concentration of 5-15 wt%, wherein the coating process control parameters comprise the pan speed requirement of 2-4 rpm before film formation, 4-7 rpm after film formation and 2-4 rpm after spraying.

Description

Dapoxetine hydrochloride tablet pharmaceutical composition and preparation method thereof Technical Field The invention belongs to the field of pharmaceutical preparations, and in particular relates to a dapoxetine hydrochloride tablet pharmaceutical composition and a preparation method thereof. Background Dapoxetine hydrochloride (chemical name: (S) -N, N-dimethyl-3- (naphthalen-1-yloxy) -1-phenylpropanamine hydrochloride) is a selective 5-hydroxytryptamine reuptake inhibitor, and has been first available worldwide as an oral medicament for treating premature ejaculation in men, improving sexual function by extending ejaculation latency (IELT), and is widely used for treating premature ejaculation. The mechanism of action inhibits reuptake of 5-HT (5-hydroxytryptamine) by neuronal presynaptic membranes, increases synaptic gap 5-HT concentration, and high concentration 5-HT activates postsynaptic receptors (e.g. 5-HT 2C), inhibits hyperexcitation of spinal ejaculation centers, thereby delaying ejaculation reflex. The peak value of the blood medicine is reached 1-2 hours after oral administration, the oral bioavailability is about 42%, the peak time of the blood medicine is about 1.3 hours, the half life period is short (about 1.5 hours), and the blood medicine needs to be rapidly dissolved to realize the curative effect. However, the existing tablets have the following problems: 1. the dissolution rate is insufficient, namely the dapoxetine hydrochloride has poor water solubility (the solubility is less than 1mg/mL at the pH of 6.8), and the dissolution rate of a conventional tablet is only 60-70% within 30 minutes, so that the requirement of quick acting is difficult to meet; 2. poor stability, which is easy to absorb moisture and agglomerate in the storage process, resulting in the reduction of dissolution and fluctuation of content; 3. the process is complex, and the traditional wet granulation requires the use of binders (such as HPMC) to increase the production steps and cost. According to the technical scheme of the patent CN104258482B (dapoxetine sustained-release pellet and the preparation process thereof), the dapoxetine drug-loaded pellet is subjected to multi-layer coating (such as ethyl cellulose and hydroxypropyl methylcellulose), so that 12-hour sustained release is realized, and the drug taking times are reduced. The process has the advantages of multiple procedures of pill making, medicine carrying, isolation layer coating, slow release layer coating and the like, long production period, high equipment requirement, precise control of air inlet temperature and spray rate of a fluidized bed coating machine, and high equipment investment and maintenance cost. Patent CN108310132a (dapoxetine orally disintegrating tablet freeze-drying process) adopts freeze-drying technology to prepare orally disintegrating tablet, so that the tablet can be quickly disintegrated in oral cavity (< 30 seconds), and patient compliance is improved. The cost is high, the energy consumption of the freeze-drying process is high, the production period is long (more than 24 hours are needed for a single batch), and the unit cost is 3-5 times of that of a common tablet. The mechanical strength is low, the freeze-dried sheet is fragile, and special protection (such as an aluminum plastic bubble cap and a drying agent) is needed in the transportation and packaging processes, so that the cost is further increased. Patent CN102526046a proposes to increase the dissolution rate by nanocrystallization technology, but the process is complex and costly. Therefore, a technical solution that is simple in process, low in cost and capable of improving the dissolution rate and stability at the same time is needed. Disclosure of Invention The invention provides a dapoxetine hydrochloride tablet pharmaceutical composition and a preparation method thereof, and the process adopts a direct mixing granulation mode, so that less equipment is used. Sodium bicarbonate is introduced as a pH regulator and a flow promoter, and dapoxetine hydrochloride with specific particle size and a drying process are combined, so that the dissolution rate is improved, the stability is enhanced, and the process is simplified. The invention controls the grain size range by controlling the grain size of the dapoxetine hydrochloride, namely the grain size of the main medicine dapoxetine hydrochloride is controlled to be 50-150 mu m, and the main medicine dapoxetine hydrochloride is realized by micronization or jet milling technology. The specific surface area of the medicine is increased, the mixing uniformity with auxiliary materials is improved, and dissolution lag or tabletting layering caused by overlarge particle size is avoided. The pH regulator has the dual functions of releasing CO 2 in a dissolution medium (such as gastric juice) to generate an alkaline microenvironment (pH is approximately equal to 8-9), promoting ionization of dapoxetine hydrochloride (we