Formulation and In-vitro Evaluation of Itraconazole Floating Microparticles

Abstract

Itraconazole (ITZ) is an antifungal drug (BCSII) used for the treatment of local and systemic fungal infections. Furthermore, ITZ used as an antifungal prophylaxis for immunocompromised patients.The objective of the study is to overcome the two problems of low and pH dependent solubility of ITZ by its preparation as floating microparticles. Firstly, pH-dependent floating microparticles were prepared using oil in water solvent evaporation method, from which the best one (F7) selected as a best pH-dependent formula with composition of ITZ (200mg),EC (800mg), HPMC 15cps (200mg) and safflower oil (2ml) .Then, F7 was compared with the selected Relatively pH-independent ITZ floating microparticles formula with composition of ITZ(200mg), a first coat of HPMC15cps (200mg), a second coat of EC (800mg), HPMC 15cps (200mg) and safflower oil (2ml) which prepared by a dual coating solvent evaporation method using a first coat which provides relatively pH-independent solubility, while the second coat applied as a bouncy producing agents. Polyvinyl alcohol (PVA) was used as a surfactant in both cases. The prepared floating microparticles were subjected to various evaluation parameters such as yield percent, drug loading and drug entrapment efficiency (EE), particle size analysis, in- vitro bouncy, drug release, Fourier Transforms Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-ray Diffractometry (XRD) studies.The selected relatively pH-independent formula (F16) has a particle size of 11.29 μm with a polydispersity index of 0.651, and the best pH-dependent formula (F7) has a particle size of 2.56 μm with PDI of 0.37. In vitro drug release per cent from the selected formula (F16) was 100 % at 10 hour (pH 1.2) while was 84% at 12 hour (pH1.2) for F7 (p > 0.05), 62 % at 12 hour (pH 3.7) for formula (F16) while was 22% at 12 hour (pH 3.7) for F7 (p < 0.05) , was 35 %at 12 hour (pH 6.8) from F16while, 7% at 12 hour (pH 6.8) from F7(p < 0.05). Therefore ITZ release from the selected formula (F16)is significantly better(p < 0.05) and the bouncy per cent of selected formula (F16) was 95% that was significantly better than bouncy percent of F7 that was 86 %( p < 0.05) in formula 16. InF7, %DL and %EE were 97% and 89%, respectively, while in F16 both %DL and %EE were 96%. FTIR results showed no change in the peaks of the ITZ microparticles functional group while XRD and DSC show change the physical state of ITZ which indicate conversion from crystalline to amorphous, which had better stability(F16).Thus, dual-coated floating microparticles (F16) appeared to be a promising approach to improve solubility at different pH values and prolong the release of the ITZ within the stomach that may increase its oral bioavailability.