Evaluation of spironolactone compatibility with magnesium stearate and other lubricants in paediatric formulation using thermal and nonthermal techniques

Abstract

Spironolactone is a potassium-sparing diuretic used as treatment for several diseases such as bronchopulmonary dysplasia, precocious puberty, hypertension or primary aldosteronism in child population. Because of the lack of paediatric formulations in the market, two types of solid oral formulation containing 2.5 and 10 mg of spironolactone were developed. During stability studies, excessive degradation was observed. As presented in this work, the degradation of spironolactone was linked to a drug excipient interaction between spironolactone and magnesium stearate via alkaline hydrolysis degradation pathway. In order to help the re-formulation with another lubricant, a complete drug excipient compatibility study was performed using thermal analysis techniques associated with chromatographic quantification of the drug after an isothermal stress testing. Spironolactone presents physicochemical incompatibilities with sodium benzoate, sodium stearyl fumarate, PEG 8000, PEG 20,000 and stearic acid. But no degradation was observed with PEG 20,000 and stearic acid indicating chemical compatibility. In total, talc, stearic acid and PEG 20,000 could be used for re-formulation of spironolactone paediatric drug.