Influence of some process and formulation variables on the formation of polymeric microspheres of itraconazole

Abstract

Itraconazole is a hydrophobic, antifungal drug. In conventional therapy, itraconazole is normally prescribed as an oral formulation at doses of 200 mg per day and 400 mg per day for serious infections, which can lead to potential toxicity. More efficient means of delivery are needed in order to reduce the toxicity of the drug with the help of reducing often drug dosing. In order to achieve this purpose modified release microspheres of itraconazole was prepared for oral administration. Itraconazole was encapsulated within ethyl cellulose microspheres by water-in-oil-in-water (w/o/w) multiple emulsion technique. Dichloromethane was used as the primary solvent for itraconazole and the polymer. Tween 80 was used as a surfactant for stabilizing external water phase and Span 80 was used for stabilizing the oil phase. The influence of various processing variables like stirring speed and production method on particle size of the microspheres were investigated. The prepared microspheres were evaluated by microscopy, yield of microspheres, particle size analysis, drug entrapment efficiency and drug release studies. Microscopy results revealed spherical nature and smooth surface morphology of the microspheres. The size of microspheres varied between 45-230 µm, and as high as 75.00 % drug entrapment efficiency was obtained depending upon the processing variables. Dissolution studies were carried out for 8 hours at pH 7.4 phosphate buffer solution (PBS) and total amount of drug released from microspheres which were preapared with a rotation speed of 900 rpm and w/o/w multiple emulsion method (F33 and F43) were between 61. 70-68.43 %, and