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CN-122003229-A - Pharmaceutical composition for improving pranlukast bioavailability and preparation method thereof

CN122003229ACN 122003229 ACN122003229 ACN 122003229ACN-122003229-A

Abstract

The present invention relates to a pharmaceutical composition for improving the bioavailability of pranlukast and a method for preparing the same, and more particularly, to a pharmaceutical composition comprising 0.1 to 10 parts by weight of a water-soluble polymer and 0.1 to 5 parts by weight of a silica-based glidant with respect to 15 to 25 parts by weight of pranlukast, so that the composition exhibits bioequivalence and even superior pharmacokinetic characteristics in the human body as compared to a commercially available preparation even if the pranlukast content is reduced to 50 mg/tablet or less (1 tablet at a time, twice daily), thereby being capable of improving the administration compliance of patients and reducing side effects caused by the administration of excessive pranlukast, and a method for preparing the same.

Inventors

  • LI ZHONGXUAN
  • QIAN YUZHEN
  • Quan Wanhu
  • Liu hengshan
  • CHEN SHOUJING
  • PU JUNYONG

Assignees

  • 达善制药株式会社

Dates

Publication Date
20260508
Application Date
20240827
Priority Date
20231012

Claims (10)

  1. 1. A pharmaceutical composition comprising: 15 to 25 parts by weight of pranlukast, 0.1 to 10 parts by weight of a water-soluble polymer, and 0.1 to 5 parts by weight of a silica-based glidant.
  2. 2. The pharmaceutical composition according to claim 1, wherein, The pranlukast has a particle size distribution of D (0, 50) of 0.1 to 2.0 μm and D (0,90) of 1.6 to 7.0 μm.
  3. 3. The pharmaceutical composition according to claim 1, wherein, The water-soluble polymer is at least one selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyethylene glycol, polyvinylpyrrolidone vinyl acetate and polyvinyl alcohol.
  4. 4. The pharmaceutical composition according to claim 1, wherein, The silica-based glidant is one or more selected from the group consisting of silicon dioxide, hard anhydrous silicon dioxide, colloidal silicon dioxide, hydrated silicon dioxide, silicate, magnesium trisilicate and magnesium aluminum silicate.
  5. 5. The pharmaceutical composition according to claim 1, wherein, The pharmaceutical composition further comprises 1 to 30 parts by weight of a solubilizing agent, which is one or more selected from the group consisting of sodium dodecyl sulfate, polyethylene glycol-15 hydroxystearate, polyoxyethylated castor oil (Cremophor), poloxamer, polyethylene glycol stearate, ethoxylated fatty alcohol, lecithin and glycerin fatty acid ester.
  6. 6. The pharmaceutical composition according to claim 1, wherein, The pharmaceutical composition further comprises 1 to 20 parts by weight of a disintegrant, wherein the disintegrant is one or more selected from the group consisting of sodium carboxymethyl starch, croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, calcium carboxymethyl cellulose and alginic acid.
  7. 7. The pharmaceutical composition according to claim 1, wherein, The pharmaceutical composition contains 50mg or less of pranlukast.
  8. 8. A method of preparing a pharmaceutical composition comprising: A step of mixing pranlukast, a diluent, a silica-based glidant and a disintegrating agent in a mixer; a step of conducting primary kneading while dissolving a water-soluble polymer in water and charging the water into the mixer, and A step of conducting secondary kneading while suspending or dissolving the solubilizing agent in ethanol and putting it into the mixer.
  9. 9. The method for preparing a pharmaceutical composition according to claim 8, wherein, 0.1 To 10 parts by weight of the water-soluble polymer is put into the mixer with respect to 15 to 25 parts by weight of the pranlukast.
  10. 10. The method for preparing a pharmaceutical composition according to claim 8, wherein, 1 To 30 parts by weight of the solubilizing agent is dosed into the mixer with respect to 15 to 25 parts by weight of the pranlukast.

Description

Pharmaceutical composition for improving pranlukast bioavailability and preparation method thereof Technical Field The present invention relates to a pharmaceutical composition for improving the bioavailability of pranlukast as a poorly soluble drug and a preparation method thereof. Background Pranlukast is very slightly soluble in water and has strong hydrophobic cohesiveness, which results in extremely low bioavailability upon oral administration, and causes a problem that the clinical administration dose is higher than the actual dose required by the patient. In view of this, korean patent No. 10-0389606 proposes a method of suspending pranlukast after dissolving saccharides, water-soluble polymer and surfactant in purified water, and spray-drying the same, thereby improving the cohesive cohesiveness of pranlukast, but failing to improve the solubility thereof. Korean patent No. 10-0381834 is a solution of pranlukast dissolved in a mixed solution of dichloromethane and methanol and prepared into a solid dispersion by spray drying, however, in order to improve the solubility and make a tablet, a large amount of disintegrant is used, resulting in the disadvantage of requiring a separate moisture-proof coating and moisture-proof packaging. Korean patent No. 10-1332223 discloses a method for preparing a nano-solid dispersion to improve the solubility of pranlukast by hot-melt method and solvent evaporation method, however, the hot-melt method faces difficulty in commercialization due to high manufacturing cost. To solve this problem, in korean patent nos. 10-1086254 and 10-1233235, in order to increase the solubility of pranlukast, a hot-melt method is used and an anti-aggregation agent having an HLB in a certain range is added, thereby preparing pranlukast solid dispersion, which is currently commercially available in Pranair capsules (pranlukast 112.5 mg/capsule, 1 capsule per administration, SK CHEMICALS). Although this product has a feature of 1/2 less dosage than Onon capsules, the hot-melt method (hot-melt) requires special manufacturing equipment and has high production cost, so that the industrial value may be low. In addition, korean patent nos. 10-0715355 and 10-0981751 are pharmaceutical compositions in the form of tablets comprising spray-dried (spray-dried) particles composed of a water-soluble polymer and a surfactant to improve the cohesive cohesiveness and solubility of pranlukast, which are currently commercially available in Prakanon tablets (75 mg/tablet of pranlukast, liu Han foreign firm per administration). However, a spray-drying (spray-drying) device has the disadvantages of complicated equipment, large volume, high disposable investment cost, low thermal efficiency and high energy consumption. In addition, the high amount of surfactant used may cause problems in the manufacturing process. The korean patent No. 10-2363727 is characterized in that pranlukast prepared by using an alcohol having 1 to 6 carbon atoms by wet granulation is contained as a pharmaceutical carrier and the amount of pranlukast taken 1 time is 70mg or less, but the amount of alcohol used in the patent is about 1 to 1.7 times that of pranlukast, which may cause environmental pollution due to an organic solvent. In addition, the use of pasty surfactants can cause differences in viscosity of the surfactant with storage temperature, which can cause problems in the manufacturing process, and ultimately can affect the density, particle size distribution, etc. of the particulate matter. As described above, although the prior patent adopts various methods for reducing the single dose of pranlukast, there is still a need for further improvement in bioavailability to reduce the dose of pranlukast, and for improving patient compliance by reducing the dose and the number of times of drug administration and reducing side effects due to high dose administration. In addition, there is a need to develop a novel preparation method which is advantageous for industrial applications. Disclosure of Invention Technical problem The invention aims to provide a pharmaceutical composition for improving the bioavailability of pranlukast and a preparation method thereof. The present invention aims to provide a pharmaceutical composition for improving the solubility of pranlukast and a preparation method thereof. Technical solution 1. A pharmaceutical composition comprising 15 to 25 parts by weight of pranlukast, 0.1 to 10 parts by weight of a water-soluble polymer, and 0.1 to 5 parts by weight of a silica-based glidant. 2. The pharmaceutical composition according to the above 1, wherein pranlukast has a particle size distribution of D (0, 50) of 0.1 to 2.0 μm and D (0,90) of 1.6 to 7.0 μm. 3. The pharmaceutical composition according to the above 1, wherein the water-soluble polymer is at least one selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyethylene glycol, polyviny