Characterization of itraconazole semisolid dosage forms prepared by hot melt technique.
The objective of this study was to formulate itraconazole semisolid dosage forms and characterize their physicochemical properties. Itraconazole and excipients such as polysorbate 80, fatty acids, fatty alcohols, oils and organic acids were melted at 160 degrees C. The fused solution was then cooled immediately at -10 degrees C to make wax-like semisolid preparations. Their physicochemical attributes were first characterized using differential scanning calorimetry, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectrometry. The solubility of itraconazole in semisolid preparations and their dispersability in the simulated gastric fluid were also determined. Our semisolid preparations did not show any distinct endothermic peak of a crystalline form of itraconazole around 160-163 degrees C. This suggested that it was changed into amorphous one, when it was formulated into semisolid preparations. In addition, the distinctive functional peaks and chemical shifts of itraconazole were well retained after processing into semisolid preparations. It could be inferred from the data that itraconazole was stable during incorporation into semisolid preparations by the hot melt technique. In particular, itraconazole semisolid preparations composed of polysorbate 80, fatty acids and organic acids showed good solubility and dissolution when dispersed in an aqueous medium. It was anticipated that the semisolid dosage forms would be industrially applicable to improving the bioavailability of poorly water-soluble drugs.
Shim
Sang-Young
SY
National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University, Chuncheon 200-701, Korea.
Ji
Chang-Won
CW
Sah
Hongkee
H
Park
Eun-Seok
ES
Lee
Beom-Jin
BJ
D002152:Calorimetry, Differential Scanning; D004304:Dosage Forms; D004344:Drug Incompatibility; D004655:Emulsions; D005079:Excipients; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents
D004304:Dosage Forms; D004655:Emulsions; D005079:Excipients; D013501:Surface-Active Agents; D017964:Itraconazole