Preparation and characterization of spironolactone-loaded nanocapsules for paediatric use

Spironolactone is a steroidal diuretic showing incomplete oral behaviour because of its low solubility and slow dissolution rate. In this study, we applied the nanoprecipitation method to prepare spironolactone-loaded nanocapsules, at laboratory-scale and pilot-scale. The effect of several formulation variables on the spironolactone-loaded nanocapsules properties (average size, drug release rate and drug entrapment) was investigated. The optimized formulations at laboratory-scale and pilot-scale lead to the preparation of spironolactone-loaded nanocapsules with a mean size of 320 and 400 nm, respectively, a high encapsulation efficiency (96.21% and 90.56% respectively), both stable for 6 months. The release of spironolactone from nanocapsules was rapid and complete in a simulated gastric fluid, therefore recourse to spironolactone nanoencapsulation should enhance its oral bioavailability and probably its efficiency. The optimized formulations lead to a high drug-concentration in the liquid preparation (1.5 mg/ml) allowing minimizing the preparation volume administered for children medication. (c) 2006 Elsevier B.V. All rights reserved.