Water Activity and Its Significance in Topical Dosage Forms

Unique properties of thermodynamic activity of solvents in topical semisolids and its effects on in vitro product performance have not been fully understood. Mechanistic investigation was undertaken to demonstrate the significance of thermodynamic potential of solvents [water activity (aw) or solvent activity (as)] on in vitro performance of model topical formulations. Drug transport across synthetic membranes was found to decrease with decreasing water activity of formulations. Similarly, in vitro permeation of model permeant (caffeine) across porcine epidermis was found to decrease with decreasing water activity of formulations. Notably, relatively low water activity formulations (aw, 0.78) induced dehydration in porcine skin associated with significant structural changes like detachment of individual stratum corneum layers. Inclusion of hydrating agents (propylene glycol) in low water activity (aw, 0.78) formulations restored hydration levels and structural integrity of porcine skin. Most importantly, incremental inclusion of propylene glycol in low water activity formulations (aw, 0.78) enhanced in vitro permeation of model permeant (fluorescein sodium). Further investigation revealed that variability in processing conditions (high shear mixing during emulsification step) could modulate water activity in semisolid formulations despite their compositional sameness. In retrospect, water activity was found to be a critical quality attribute of topical semisolid products which impacts overall product performance and drug delivery.