Mechanistic studies to elucidate the role of lipid vehicles on solubility, formulation and bioavailability of poorly soluble compounds
Lipids have been used to improve the bioavailability of poorly soluble drugs for almost twenty years. However, they are still not well characterized. There are limited publications about the effects of physicochemical properties of the lipid vehicle, such as class of lipid, chain length, MW and polarity on lipid solubility, formulation and bioavailability of poorly soluble drugs. The goals of this study are to identify physicochemical properties of lipids, to investigate their effects on the solubility of model drugs, nifedipine and griseofulvin, on dissolution of nifedipine from lipid-based formulations and on the bioavailability of nifedipine. The lipids used improved the solubility of nifedipine and griseofulvin compared to the solubility of drugs in water. Calculated and measured properties of lipids analyzed with stepwise regression analyses showed that MW, dielectric constant, surface tension and fatty acid chain length are the common factors that govern the lipid solubility. Different estimates of each factor for each drug indicated the drug played important role in lipid solubility. Incorporation of Cremophor EL into lipid-based nifedipine formulation enhanced the solubility and dissolution of nifedipine. The solubility of nifedipine showed a linear correlation with surfactant concentration. While solubility rate was dependent on the type of lipid used, the dissolution of nifedipine in presence of surfactant was the same regardless of lipid used. The effect of lipids on dissolution performance of nifedipine investigated showed that even though physicochemical properties of lipids (HLB, interfacial tension, viscosity, density and chain length) and solubility of nifedipine in lipids play role, partitioning of the drug from lipid to aqueous medium and particle size of the formulation in dissolution medium were provided a good correlation with dissolution of nifedipine. Bioavailability of nifedipine obtained with different lipid formulations in beagle dogs showed that the type lipid and surfactant used in the formulation play important role. Although, the solubility of nifedipine in lipids, particle size of the formulation in dissolution medium and partitioning of the drug from the formulation to dissolution medium seem to affect the in vivo performance of the drug, dissolution performance of the formulation and digestibility of the lipid played the major role. ^
Health Sciences, Pharmacy
"Mechanistic studies to elucidate the role of lipid vehicles on solubility, formulation and bioavailability of poorly soluble compounds"
Dissertations and Master's Theses (Campus Access).