Formulation and Evaluation Monoporous Hollow Microspheres of Itraconazole- for Pulmonary Drug Delivery
Background: Itraconazole is a broad-spectrum triazole antifungal drug, but its poor aqueous solubility, variable oral bioavailability and first-pass metabolism limit predictable therapeutic exposure. Pulmonary delivery can provide high local antifungal concentration in lung tissues while reducing systemic exposure. Objective: The present study aimed to formulate, optimize and evaluate itraconazole-loaded monoporous hollow microspheres as a sustained pulmonary drug delivery system. Methods: Microspheres were prepared by an emulsion solvent evaporation technique using PLGA and Eudragit RS100 as release-retarding polymers and ammonium bicarbonate as a gas-forming pore-forming agent. Formulations F1-F9 were prepared according to a factorial design and evaluated for preformulation attributes, drug-excipient compatibility, particle size, percentage yield, entrapment efficiency, morphology, mass median aerodynamic diameter (MMAD), flow properties, in-vitro drug release and accelerated stability. Results: Itraconazole was practically insoluble in water and showed lambda max at 262 nm in methanol. FTIR and DSC studies indicated no major drug-excipient incompatibility. Particle size ranged from 1.8 to 3.6 µm and entrapment efficiency from 70 to 99%. Batch F3, containing 100 mg itraconazole, 250 mg PLGA, 500 mg Eudragit RS100 and 50 mg ammonium bicarbonate, was optimized because it showed mean particle size of 2.4 µm, yield of 88%, entrapment efficiency of 99%, spherical hollow porous morphology, MMAD of 2.9 µm, Carr index of 16.7%, Hausner ratio of 1.20 and 95% drug release at 8 h. After 3 months, F3 retained particle size of 2.5 µm, entrapment efficiency of 97.9%, MMAD of 2.8 µm and 87.8% cumulative release at the stability endpoint. Conclusion: The optimized itraconazole monoporous hollow microspheres demonstrated suitable micromeritic, aerodynamic, entrapment and sustained-release characteristics, supporting their further investigation as a pulmonary antifungal delivery platform.