WATER-SOLUBLE BETA-CYCLODEXTRINS IN PEDIATRIC ORAL SOLUTIONS OF SPIRONOLACTONE - SOLUBILIZATION AND STABILITY OF SPIRONOLACTONE IN SOLUTIONS OF BETA-CYCLODEXTRIN DERIVATIVES

Water-soluble beta-cyclodextrins, hydroxypropyl-beta-cyclodextrin (HP beta CD), dimethyl-beta-cyclodextrin (DM beta CD) and sulphobutyl ethe r beta-cyclodextrin (SBE7), were evaluated as potential solubilizers o f spironolactone (SP) in paediatric enteral formulations. H-1-NMR was used to verify the formation of inclusion complexes and to detect poss ible degradation of spironolactone through deacetylation. The effect o f temperature on spironolactone stability was studied in solutions of HP beta CD and SBE7 to estimate shelf-lives of possible liquid prepara tions. HP beta CD, DM beta CD and SBE7 formed true inclusion complexes with spironolactone with a stoichiometry of 1:2 (SP:beta CD). No degr adation of spironolactone could be detected in the presence of DM beta CD, whereas spironolactone degraded through deacetylation according t o pseudo-first order kinetics in the presence of HP beta CD and SBE7. Spironolactone degradation was slower in solutions of SBE7 than in HP beta CD, with the slowest degradation at 6 degrees C in SBE7 solution. Estimated shelf-lives (t(90%)) for solutions containing 3 mg/ml of sp ironolactone were, even at 6 degrees C, below 2 h in the presence of H P beta CD. The t(90%)-values in the presence of SBE7 were 4.1, 8.3 and 24.5 h at 22, 13 and 6 degrees C, respectively. According to these re sults, SBE7 could be considered for the solubilization of spironolacto ne in paediatric enteral solutions, if the solution were to be prepare d and stored at 6 degrees C or below. (C) 1997 Elsevier Science B.V.