Statistical optimization for production of mefenamic acid-nicotinamide and mefenamic acid-paracetamol cocrystals using gas anti-solvent (GAS) process

Name: Napada Wichianphong

LCSH: Kasetsart University -- Dissertations. Ph.D. (Chemical Engineering) 2018

Classification :.LCCS: TP156.E8

LCSH: Kasetsart University. -- Department of Chemical Engineering -- Dissertations

LCSH: Supercritical fluids

LCSH: Mefenamic acid

LCSH: Nicotinamide

LCSH: Drugs -- Solubility

LCSH: Crystallization

LCSH: Solvent extraction

Abstract: In this research, mefenamic acidnicotinamide (MEFNIC) and mefenamic acidparacetamol (MEFPAR) cocrystals were produced using gas anti-solvent (GAS) process in order to improve dissolution rate of mefenamic acid (MEF). BoxBehnken design was used to optimize the GAS process variables for minimal dissolution time of MEF. Mathematical model were developed to study the effects of operating temperature, conformer-to-MEF molar ratio and % MEF saturation in the ranges of 25 oC-45 oC, 3:1-5:1 and 70-90%, respectively. In the case of MEFNIC cocrystals, the analysis of experimental design showed that coformer-to-drug molar ratio and %drug saturation are significant parameters affecting the dissolution rate of the cocrystals. At a temperature of 45 oC, coformer-to-drug ratio of 5 and %drug saturation of 70% were found to be the optimal conditions for achieving the fastest dissolution time. Sieved cocrystals obtained from the optimal conditions showed an enhanced dissolution rate 38 times greater than that of pure MEF and 1.6 times greater than sieved cocrystals from a traditional slow evaporation method. In the case of MEFPAR cocrystals, PAR-to-MEF ratio and %MEF saturation were found to be the main parameters affecting the dissolution time. The fastest dissolution time (t63.2), 11.38 minutes, was obtained at the optimal conditions of a temperature of 34.9 oC, PAR-to-MEF ratio of 4.3:1 and MEF saturation of 86.8%. Optimized cocrystals by GAS showed that the dissolution rate of MEF improved by 6.0, 5.3 and 2.3-fold when compared to pure MEF, sieved cocrystals prepared by a slow evaporation technique and sieved marketed combination drugs, respectively. GAS cocrystallization thus offers an efficient way to enhance the dissolution rate of the poorly water-soluble drug. Moreover, the dissolution properties of both the MEFNIC and the MEFPAR cocrystals were found to be stable after storage at ambient temperature and 40-50 % relative humidity for three months.

Kasetsart University. Office of the University Library

Address: Bangkok

Email: tdckulib@ku.ac.th

Name: Manop Charoenchaitrakool

Role: Thesis Advisor

Name: Supacharee Roddecha

Role: Thesis CO-Advisor

Created: 2018

Modified: 2025-07-03

Issued: 2025-07-03

วิทยานิพนธ์/Thesis

application/pdf

URL: https://www.lib.ku.ac.th/KUthesis/2561/napada-wic-all.pdf

CallNumber: TP156.E8 .N37

eng

DegreeName: Doctor of Philosophy

Level: Doctoral Degraee

Descipline: Chemical Engineering

Grantor: Kasetsart University

©copyrights Kasetsart University

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