Flurbiprofen acetaminophen ester solid dispersion and preparation method thereof

A technology of acetaminophen ester and solid dispersion, which is applied in the directions of non-active ingredient medical preparations, active ingredients-containing medical preparations, pharmaceutical formulas, etc., can solve problems such as poor solubility and low bioavailability

Inactive Publication Date: 2014-04-09
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Starting from the actual market application, this project adopts solid dispersion technology with strong operability to solve the problem of low bioavailability in vivo of flurbiprofen acetaminophen ester due to poor solubility

Method used

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  • Flurbiprofen acetaminophen ester solid dispersion and preparation method thereof
  • Flurbiprofen acetaminophen ester solid dispersion and preparation method thereof
  • Flurbiprofen acetaminophen ester solid dispersion and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1: the preparation of flurbiprofen acetaminophen ester

[0034] Weigh 100g (410mmol) flurbiprofen into a round-bottomed flask, add dichloromethane dropwise while stirring until flurbiprofen is completely dissolved in an ice bath, then slowly add the last 45mL (614mmol) dichloromethane Sulfoxide, reacted at room temperature for 6 hours, and evaporated the solvent to obtain 105.5 g of flurbiprofen acyl chloride, with a yield of 98%. Weigh 73g (792mmol) of acetaminophen and place it in a round-bottomed flask, dichloromethane solvent, under ice-bath conditions, slowly add 112mL (803mmol) of triethylamine dropwise, and then the flurbirol dissolved in dichloromethane Fenyl chloride was slowly added dropwise to the acetaminophen solution. Remove the ice bath and react for 6 hours.

[0035] After the reaction, extract with water three times (200mL×3), extract with sodium bicarbonate solution three times (200mL×3), dry the organic phase with anhydrous magnesium sulf...

Embodiment 2

[0043] Take 5g of flurbiprofen acetaminophen ester, dissolve it in ethanol solution, heat PEG400020g to 80°C to form a molten state, slowly add flurbiprofen acetaminophen ester alcohol solution dropwise to the carrier material, stir, and evaporate to dryness Ethanol, quickly moved to -20 ℃ solidified for 4h. The resultant was taken out, pulverized, and dried. That is, solid dispersion powder is obtained. The solid dispersion of the inventive process has an in vitro cumulative dissolution rate of 93.5±3.1% (n=6) within 45 minutes. Six samples were measured in parallel.

Embodiment 3

[0045] Take flurbiprofen acetaminophen ester 5g, dissolve in appropriate ethanol, dissolve PVP-S630 in ethanol, heat at 60°C, mix the above two solutions evenly, stir for 2 hours, evaporate the ethanol, and quickly move to Curing at -20°C for 8 hours. The resultant is taken out, pulverized, and dried to obtain a solid dispersion powder. The solid dispersion of the inventive process has an in vitro cumulative dissolution rate of 94.4±3.6% (n=6) within 45 minutes. Six samples were measured in parallel.

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Abstract

The present invention relates to a flurbiprofen acetaminophen ester solid dispersion and a preparation method thereof, wherein the main component of the anti-inflammatory and analgesic prodrug is a complete-new compound flurbiprofen acetaminophen ester. According to the present invention, a hydrophilic carrier material is added, a solvent method and a solvent-melting method are respectively adopted to prepare the flurbiprofen acetaminophen ester solid dispersion, and the flurbiprofen acetaminophen ester solid dispersion can further be mixed with suitable auxiliary materials so as to prepare oral tablets or capsules; and the dissolubility and the dissolution rate of the drug can be significantly increased, the dissolubility of the drug is increased by 10-100 times compared with the raw material drug, and the 45 min accumulation dissolution percentage in the dissolution medium is correspondingly and substantially increased so as to improve the oral absorbability of the drug.

Description

technical field [0001] The invention belongs to the field of pharmaceutical manufacturing, and in particular relates to a flurbiprofen paracetamol solid dispersion and a preparation method thereof. Background technique [0002] Non-steroidal anti-inflammatory analgesics (NSAIDs) are the fastest-growing drugs in the world, and are widely used to treat arthritis, especially various inflammatory pains caused by osteoarthritis and rheumatoid arthritis. Different types of NSAIDs have the same mechanism of action [Curr.Opin.Rheum.1996, 8:169–175], all of which inhibit the activity of cyclooxygenase, thereby inhibiting the formation of the inflammatory response factor prostacyclin from arachidonic acid (PGI1), prostaglandins (PGE1, PGE2) and thromboxane A2 (TXA2). Such drugs are more likely to cause side effects such as gastrointestinal ulcers, bleeding, and even perforation [Br J Pharmacol.1999Nov, 128(6):1121-32.]. [0003] Flurbiprofen is an arylpropionic acid non-steroidal an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K31/216A61K47/34A61K47/32A61K47/38A61P29/00
Inventor 杨凌葛广波邹超宁静洪沫王平
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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