Application of Hildebrand Solubility Parameter to Identify Ethanol-Free Co-Solvent for Pediatric Formulation

Formulation of active pharmaceutical ingredients into liquid dosage form is frequently limited by solubility issues. Ethanol is commonly used as a cosolvent to improve the solubility of drugs. Due to the incomplete expression of ethanol metabolizing enzyme in children under 6 years, several drug authorities such as WHO, EMA, and FDA recommend avoiding the use of ethanol in pediatric formulation whenever possible. In addition, Muslim consumers are regulated by the halal practice where excessive use of ethanol in pharmaceutical products should be avoided. Thus, it is necessary to explore an alternative co-solvent to reduce the use of ethanol in pediatric formulation. This study is aimed to identify an alternative co-solvent to ethanol that is safe for the pediatric using Hildebrand Solubility Parameter approach. In this study, the solubility parameter of the model drug, MH2011, was determined using Hildebrand Solubility Parameter (HSP). The solubility parameter (δ) of MH2011 was determined using two approaches. The first method is by measuring the maximum solubility of the model drugs in the binary mixture of water and 1,4 dioxane. The second approach is by calculating solubility parameters based on Fedor’s group substitution method. Using a binary solvent blend, the MH2011 solubility parameter was identified. MH2011 solubility parameter is comparable to those calculated using Fedor’s Group substitution method. Data on the solubility parameter has then been used to identify the alternative solvent to ethanol. The studies also implied that propylene glycol 7 v/v gave similar solubility power as those of ethanol 7 (v/v). This study suggested that Hildebrand’s Solubility Parameter can be applied to identify an alternate co-solvent to ethanol when an alcohol-free formulation is preferred; such as in halal pharmaceuticals and pediatric liquid formulations. Copyright © 2023 by Indonesian Journal of Pharmacy (IJP)