Hydrocortisone nanosuspensions for ophthalmic delivery: A comparative study between microfluidic nanoprecipitation and wet milling.

Recently, drug nanosuspensions have shown a potential for ophthalmic delivery. In this study, a hydrocortisone (HC) nanosuspension (NS) was developed using microfluidic nanoprecipitation as a recent, simple and cost-effective bottom-up technique of drug nanonization. For comparison, a second HC NS was prepared by top-down wet milling procedures. The produced nanosuspensions were characterized for particle size, shape and zeta potential. HC nanosuspensions of approximately 300nm particle size were produced by adjusting experimental conditions of the two processing techniques. Results of X-ray diffraction and differential scanning calorimetry revealed that HC maintained the crystalline structure upon milling, while predominant amorphous particles were generated after precipitation. Ocular bioavailability of HC nanosuspensions was assessed in albino rabbits using HC solution as a control. A sustained drug action was maintained up to 9h for the nanosuspensions compared to 5h for the drug solution. The precipitated and milled NS achieved comparable AUC(0-9h) values of 28.06±4.08 and 30.95±2.2, respectively, that were significantly (P<0.05) higher than that of HC solution (15.86±2.7). After 2 months storage at room temperature, the milled HC NS showed good stability with no discernable changes in particle size, whereas the particle size of the precipitated HC NS increased to 440nm.