International Journal of Pharmaceutics 2004-01-28

Poly(epsilon-caprolactone) and Eudragit microparticles containing fludrocortisone acetate.

Stéphane Gibaud, Najim Jabir Al Awwadi, Camille Ducki, Alain Astier

Index: Int. J. Pharm. 269(2) , 491-508, (2004)

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Abstract

Substitutive hormonal therapies have to be administered for long periods. Thus, the development of sustained-release forms, as microparticle suspensions, is interesting in order to improve patient compliance by reducing dosing frequencies and side effects. The aim of this work was to compare different formulations of fludrocortisone microparticles for the treatment of mineralocorticoid insufficiency. The study was done with different polymers (poly(epsilon-caprolactone), Eudragit RS and Eudragit RL) and different processes (O/W solvent evaporation methods and S/O/W evaporation methods). The use of a suspension of micronized drug in dichloromethane as dispersed phase (S/O/W method) significantly improved the process. Whereas low concentrations of FLU dissolved in the dispersed phase led to smooth-surface homogeneous microparticles and poor incorporation efficiency (5.8-7.3%); suspensions of FLU led to microparticles with numerous crystals on their surfaces (S/O/W microparticles) and high incorporation efficiency (about 79%). However, the best release profiles were obtained with microparticles prepared with 7.5 mg/ml of dichloromethane, near saturation. Moreover, the use of mixtures of poly(epsilon-caprolactone), Eudragit RS and RL did not improve the release profiles.