Dissolution rate of cholesterol and palmitic acid mixtures in cholelitholytic cosolvent systems.
The dissolution rates and solubilities of cholesterol monohydrate, palmitic acid, and their mixtures in the cholelitholytic solvents monooctanoin (MO) and methyl tert-butyl ether (MTBE) and mixtures of these two solvents were determined. The dissolution rates obtained were consistent with the diffusion-controlled two-component noninteracting model. The addition of MTBE as cosolvent to MO resulted in an increase in the solubility of both cholesterol monohydrate and palmitic acid; in the case of the former, the solubility peaked at 80% MTBE. Neither solute exhibited a log-linear solubility relationship on addition of MTBE as cosolvent. Furthermore the increases in the dissolution rates of both components were much larger than could be explained by the solubility increases alone. Mass transfer coefficients increased dramatically with increasing MTBE content of the solvent, were consistently higher for palmitic acid, and reflected the decline in solvent viscosity. Incorporation of relationships among solubility, viscosity, and cosolvent composition into the two-component noninteracting model gave good correlation between predicted and observed rates over nearly 3 orders of magnitude.
O'Reilly
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Department of Pharmaceutics, School of Pharmacy, Trinity College, Dublin, Ireland.
Corrigan
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D002210:Caprylates; D002769:Cholelithiasis / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry*; D002849:Chromatography, Gas; D004058:Diffusion; D004987:Ethers; D005989:Glycerides; D007700:Kinetics; D008738:Methyl Ethers; D008954:Models, Biological; D010169:Palmitic Acids / Q000737:chemistry*; D012995:Solubility; D012997:Solvents; D014783:Viscosity
D002210:Caprylates; D004987:Ethers; D005989:Glycerides; D008738:Methyl Ethers; D010169:Palmitic Acids; D012997:Solvents; C043243:methyl tert-butyl ether; D002784:Cholesterol; C025343:monooctanoin