Using natural excipients to enhance the solubility of the poorly water-soluble antiretroviral, efavirenz

The anti-retroviral drug efavirenz (EFV) exhibits poor aqueous solubility which renders pharmaceutical formulation challenging. During a pre-formulation phase, involving spray drying of EFV for pediatric dosage form development, the combination of EFV with two natural excipients, pea protein isolate (PPI) and inulin (IN), was explored. In this study the effect of PPI and IN on the solubility of EFV became apparent, leading to an indepth investigation. Equilibrium solubility studies were performed for different combinations of EFV, PPI, and IN in distilled water and buffered solutions in the presence and absence of commonly used surfactants, Tween (R) 20 and sodium lauryl sulfate (SLS). In the combination of EFV and PPI, PPI significantly improved EFV solubility while in the combination of EFV and IN, EFV solubility was not affected significantly. In the combination of EFV, PPI, and IN, a significant solubility improvement was noted, yet the degree of solubility improvement was less compared to the combination of only EFV and PPI. Further, the effects of PPI and IN on the solubility prove to be concentration-related. It was concluded that PPI can be used as a functional excipient to improve EFV solubility, conversely IN can be used as a drug dissolution retardant, and finally it was also concluded that it is crucial to optimize the ratio of drug to excipient to ensure optimal pharmaceutical formulation outcomes.