Spray-Dried Redispersibie Emulsion to Improve Oral Bioavailability of Itraconazole

摘要

Dry emulsions are powdery, lipid-based formulations from which an o/w-emulsion can be easily reconstituted in vivo or when exposed to water. The objective of this work was to prepare and characterize dry emulsion of itraconazole (ITZ) to improve its solubility and bioavailability. Dry emulsions were prepared by spray-drying liquid o/w-emulsions containing carriers like mal-todextrin, sucrose, and lactose. Propylene glycol mono-caprylate was selected as oil phase, and surfactant blends of vitamin E tocopherol polyethylene glycol succinate and triblock PEO-PPO-PEO copolymer as emulsifying agents. Several oil:water and carrienwater ratios were tested. An optimum formulation was selected using 32 full factorial design. The droplet size, rheological behavior, and drug release from o/w-emulsion before and after reconstitution and the micromeritic properties of spray-dried product were investigated. Maltodextrin was used as a carrier for preparing dry emulsions. The optimized dry emulsion was characterized using DSC, SEM, PXRD, and in vivo study. The SEM analysis showed that dry emulsion consisted of well-separated particles with smooth surfaces. The DSC and XRD study showed that ITZ in the dry emulsion is in the molecular dispersion state. Globule size analysis showed that dry emulsion had good reconstitution properties. The emulsions were found to be thermodynamically stable when subjected to cyclical freeze-thaw cycles and centrifugation tests. The average globule size of emulsions ranged from 0.994 to 1.668 μm. A 71.35 % increase in C_(max) and 114.78 % increase in AUC was evident for ITZ dry emulsion as compared to plain ITZ.