Assessment of solubility and Hansen solubility parameters of rifampicin in various permeation enhancers: Experimental and computational approach

摘要

The study aimed to investigate quantitative solubility of rifampicin (RIF) coupled with a computational validation in various permeation enhancers such as surfactants [Span 80, Transcutol HP (THP), and triacetin], lipids [limonene, isopropyl myristate (IPM), and eugenol], and organic solvents [ethanol, 2-butanol, isopropyl alcohol (IPA), and ethyl acetate (EA)]. Several experimental and computational strategies estimated the solubility of RIF at T = 298.2 to 318.2 K and p = 0.1 MPa. The estimated experimental solubility data were validated using van't Hoff and Apelblat models. The software HSPiP was used to identify the best permeation enhancer for RIF. The mole fractional solubilities of RIF in permeation enhancers were calculated and found to be in the order: limonene (9.6 x 10(-2)) > IPM ( 5.3 x 10(-2)) > THP (1.8 x 10(-2)) > EA (1.3 x 10(-2)) > IPA ( 1.7 x 10(-3)) > Span 80 (9.9 x 10(-4)) > triacetin (8.8 x 10(-4)) > eugenol (5.9 x 10(-4)) > ethanol (5.3 x 10(-4)) = 2-butanol (5.3 x 10(-4)) at T = 318.2 K. Similar patterns for the solubility were obtained at the other temperatures explored (T = 298.2, 303.2, 308.2, and 313.2 K). The solubility parameters were observed to be closest to those for RIF for limonene, IPM, and THP, suggesting RIF will have good solubility in these permeation enhancers. Moreover, an apparent thermodynamic analysis estimated various thermodynamic parameters for dissolution and suggested that the dissolution of RIF in permeation enhancers is endothermic and driven by entropy. The activity coefficients confirmed that there were significant solute-solvent interactions between RIF and limonene, RIF and IPM, and RIF and THP. Thus, limonene, IPM, and THP may be the best solvents with the maximum RIF solubility and miscibility for transdermal or oral administration. (C) 2021 Elsevier B.V. All rights reserved.