The variation in the critical formulation variables during life-cycle of the drug product may result in undesirable changes in product performance. The current study aimed at evaluating the effects of formulation variables on the in vitro performance of carbopol-loaded testosterone gel. The formulation variables included concentrations of permeation enhancers, testosterone, ethanol, carbopol and sodium hydroxide. In vitro evaluation of the product performance included assessment of the rheological and morphological properties, kinetics of ethanol evaporation, and drug permeation through human cadaver skin. The results revealed that carbopol, sodium hydroxide and testosterone concentrations increased the viscosity of the gels significantly (p < 0.05). However, carbopol concentration was the only critical variable to affect the yield stress of the gel. The concentration of ethanol was critical to metamorphosis of the gel due to solvent evaporation upon application to skin with minor contributions from other formulation variables. The increase in concentration of isopropyl myristate or isopropyl palmitate to 5%, ethanol to 70%, and testosterone to 2%, enhanced the testosterone permeation across the skin by ten-folds. Synergistic effects of ethanol and permeation enhancers on testosterone permeation was observed. In conclusion, strict control over the critical formulation variables should be exercised during manufacturing to ensure desired product performance.
Keywords: Formulations variables; In vitro performance; Permeation; Quality attributes; Rheology; Testosterone.
Published by Elsevier B.V.