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Tolvaptan oral preparation and preparation method thereof

A technology of tolvaptan and oral preparations, applied in the field of chemical pharmaceuticals, can solve the problems of affecting bioavailability, dissolution rate reduction, etc., and achieve the effect of ensuring bioavailability

Active Publication Date: 2021-07-27
NANJING HEALTHNICE MEDICAL TECH +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Cross-linked polyvinylpyrrolidone and highly substituted hydroxypropyl cellulose are both water-soluble carriers. They are made into immediate-release solid dispersions. Too high, supersaturated and precipitated, resulting in reduced dissolution rate, thus affecting bioavailability
[0007] Chinese patent CN101686941A discloses a pharmaceutical solid preparation containing benzazepine And its production method, mentioning dispersion preparation process in the embodiment, adopting carrier is hydroxypropyl cellulose, and hydroxypropyl cellulose is water-soluble carrier, is prepared into quick-release solid dispersion, quick-release solid dispersion After dissolving in the gastrointestinal tract, it will be precipitated due to high local concentration and supersaturation, which will affect the bioavailability
Highly substituted hydroxypropyl cellulose is a water-soluble carrier, and it is made into an immediate-release solid dispersion. After dissolving in the gastrointestinal tract, it will precipitate due to excessive local concentration and supersaturation, resulting in a decrease in dissolution rate and thus affecting bioavailability

Method used

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  • Tolvaptan oral preparation and preparation method thereof
  • Tolvaptan oral preparation and preparation method thereof
  • Tolvaptan oral preparation and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0045] Weigh 100 g of tolvaptan bulk drug and 50 g of hydroxypropyl cellulose, add them into 350 g of absolute ethanol and 1150 g of dichloromethane mixed solvent, and stir to dissolve. Use an explosion-proof closed-type nitrogen circulation spray dryer for spray drying, set the inlet air temperature to 100°C; the rotation speed of the atomization disc is 30,000rpm, the liquid supply speed is 5kg / h, and the outlet air temperature is 40-70°C, pump the mixed solution with a peristaltic pump Put it into a spray dryer, dry under reduced pressure at 40°C for 12 hours, remove organic reagents, and pass through a 40-mesh sieve to obtain a water-soluble solid dispersion.

Embodiment 2

[0047] Weigh 100 g of tolvaptan bulk drug and 100 g of hypromellose phthalate, add them to 900 g of absolute ethanol and 1650 g of dichloromethane mixed solvent, and stir to dissolve. Use an explosion-proof closed-type nitrogen circulation spray dryer for spray drying, set the inlet air temperature to 100°C; the rotation speed of the atomization disc is 30,000rpm, the liquid supply speed is 5kg / h, and the outlet air temperature is 40-70°C, pump the mixed solution with a peristaltic pump Put it into a spray dryer, dry under reduced pressure at 40°C for 12 hours, remove organic reagents, and pass through a 40-mesh sieve to obtain an enteric solid dispersion.

Embodiment 3

[0049] Weigh 100 g of tolvaptan bulk drug and 50 g of hydroxypropyl cellulose, add them into 700 g of absolute ethanol and 2300 g of dichloromethane mixed solvent, and stir to dissolve. Use an explosion-proof closed-type nitrogen circulation spray dryer for spray drying, set the inlet air temperature at 140°C; the rotation speed of the atomization disc is 30,000rpm, the liquid supply speed is 10kg / h, and the outlet air temperature is 80-110°C, pump the mixed solution with a peristaltic pump Put it into a spray dryer, dry under reduced pressure at 40°C for 12 hours, remove organic reagents, and pass through a 40-mesh sieve to obtain a water-soluble solid dispersion.

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Abstract

The invention relates to a tolvaptan oral preparation and a preparation method thereof. The preparation method comprises the following steps: firstly, dispersing a tolvaptan bulk drug into a carrier-hydroxypropyl cellulose and an organic solvent; dispersing the tolvaptan bulk drug in a carrier-hydroxypropyl methylcellulose phthalate and an organic solvent, respectively carrying out spray drying by adopting an explosion-proof closed nitrogen circulation spray dryer, and strictly controlling process parameters in the spray drying process, and drying under reduced pressure to prepare two solid dispersions of tolvaptan: a water-soluble solid dispersion and an enteric solid dispersion, wherein the two solid dispersions are then combined with excipients to prepare tolvaptan oral preparations, the quick-release solid dispersion is dissolved in the stomach, the enteric-soluble solid dispersion is dissolved in the intestinal tract, so that the condition of precipitation caused by overhigh local concentration and oversaturation is reduced, and the bioavailability of the medicine can be better ensured.

Description

technical field [0001] The invention belongs to the technical field of chemical pharmacy, and relates to a tolvaptan oral preparation and a preparation method thereof. Background technique [0002] Tolvaptan (Tolvaptan), the chemical name is N-[4-[(5R)-7-chloro-5-hydroxy-2,3,4,5-tetrahydro-1-benzazepine -1-formyl]-3-methylphenyl]-2-methylbenzamide, the structural formula is as follows: [0003] [0004] Tolvaptan is a white crystal or crystalline powder, slightly soluble in methanol or ethanol (99.5), almost insoluble in water, belongs to BCS IV drugs, has low solubility and low permeability properties, and needs to improve its physical and chemical properties to increase its solubility and permeability to achieve the effect of improving dissolution and bioavailability. [0005] Solid dispersion refers to a dispersion system in which a drug is highly dispersed in a water-soluble material, insoluble or enteric-soluble material in a molecular or amorphous state. Immedia...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K31/55A61K47/38A61K9/20
CPCA61K31/55A61K9/146A61K47/38A61K9/0053A61K9/2059
Inventor 李永亮郁蕾蕾王华娟
Owner NANJING HEALTHNICE MEDICAL TECH
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