Comparison of the mechanism of dissolution of hydrocortisone in simple and mixed micelle systems.
Lecithin, a major phospholipid component of human bile, is instrumental in the formation of mixed micelles in vivo, with implications for the dissolution and absorption of poorly soluble compounds administered orally. Hydrocortisone, a poorly aqueous soluble drug (Saq = 1.08 x 10(-3) M), was chosen to compare the rate and mechanism of dissolution in a NaTC/lecithin (mixed micelle) system with its NaTC-only (simple micelle) counterpart. Surface tension, solubility studies, contact angles, rotating disk dissolution rates, and powder dissolution rates were compared for hydrocortisone between solutions containing NaTC/lecithin (4:1) and NaTC-only under conditions representative of the small intestine (0-30 mM NaTC, pH 5.5, 0.1 M NaCl). At all concentrations, the solubility of hydrocortisone in NaTC/lecithin was slightly higher (up to twofold) than in the corresponding NaTC-only solutions. At low NaTC concentrations, initial powder dissolution rates were faster in the NaTC/lecithin solutions than in corresponding NaTC-only solutions. In contrast, at high NaTC concentrations, initial powder dissolution rates in the NaTC-only solutions were faster. Results indicated that in the NaTC-only system wetting effects predominated for dissolution, while in the NaTC/lecithin system, the dissolution rate of hydrocortisone was enhanced mainly via solubilization.
Naylor
L J
LJ
University of Michigan College of Pharmacy, Ann Arbor 48109-1065.
Bakatselou
V
V
Dressman
J B
JB
D001647:Bile Acids and Salts / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D006801:Humans; D006854:Hydrocortisone / Q000737:chemistry*; D008823:Micelles; D010713:Phosphatidylcholines / Q000737:chemistry; D012995:Solubility; D013500:Surface Tension
D001647:Bile Acids and Salts; D008823:Micelles; D010713:Phosphatidylcholines; D006854:Hydrocortisone