Development, Physical-Chemical Stability, and Release Studies of Four Alcohol-Free Spironolactone Suspensions for Use in Pediatrics

Abstract

Dissolution studies have become of great significance because, in most cases, drug dissolution is the rate-limiting step in the absorption process. As occurs with solid oral dosage forms, heterogeneous dispersed systems (suspensions) could also have some problems with their in vitro dissolution. The objective of this study was to evaluate the influence of excipients on the release of spironolactone from four alcohol-free suspensions (pharmaceutical compounding) of spironolactone 5 mg/mL suitable for pediatric use. In addition, the comparison of the physical and chemical stability of the suspensions stored at 4, 25, and 40 °C over a 60-day period has been studied. Rheological behavior, particle size, a prediction of long-term physical stability, pH, and assay of spironolactone by HPLC were assessed at preset times. The dissolution profile of each suspension was determined and compared with that of the commercial tablets. A microbiological study of the best formula was also performed. Chemically, the four spironolactone suspensions were stable for 60 days stored at three temperatures; Suspension IV had optimum pH values and the highest recovery percentage. In terms of physical stability, sedimentation occurred in Suspension IV, and flotation of spironolactone occurred in Suspensions I, II, and III. Suspension III had the highest viscosity and the slowest drug release. Suspension IV was also microbiologically stable for 60 days. In conclusion, Suspension IV had the best properties. The least suitable form was Suspension III, as its high viscosity made it difficult to achieve homogeneous redispersion and it had the slowest dissolution profile.