Poly(ε-caprolactone) and Eudragit ® microparticles containing fludrocortisone acetate

• Published in: International journal of pharmaceutics Vol. 269; no. 2; pp. 491 - 508
• Main Authors: Gibaud, Stéphane, Jabir Al Awwadi, Najim, Ducki, Camille, Astier, Alain
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28.01.2004; Elsevier
• Subjects: Biological and medical sciences; Chemistry, Pharmaceutical; Chemistry, Pharmaceutical - methods; Delayed-Action Preparations; Fludrocortisone; Fludrocortisone - analogs & derivatives; General pharmacology; Life Sciences; Medical sciences; Microparticles; Particle Size; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polycaprolactone; Polyesters; Polymer; Polymethacrylic Acids; Sustained release; Fludrocortisone; Polymer; Sustained release; Polycaprolactone; Microparticles; Corticosteroid; Controlled release form; Steroid hormone; Formulation; Adrenal hormone; Dosage form; Microparticle
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2003.09.040

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(ε-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(ε-caprolactone), Eudragit ® RS and RL did not improve the release profiles.