Isotropic Systems of Medium‐Chain Mono‐ and Diglycerides for Solubilization of Lipophilic and Hydrophilic Drugs

Abstract

The aim of this study was to investigate isotropic mono‐ and diglyceride‐based (MCMDG) systems, which are potential vehicles for injectable products containing both hydrophilic and lipophilic drugs. For two‐component systems, MCMDG was mixed with various masses of water. For three‐component systems, the samples were prepared by mixing propylene glycol or glycerol formal or short‐chain alcohols with MCMDG prior to the addition of water. The isotropic region was examined by visual inspection and confirmed using polarized light microscopy. Viscosities of formulations were measured. Solubilities of levamisole phosphate (hydrophilic) and abamectin (lipophilic) were determined in the isotropic formulations using high‐performance liquid chromatography assay. The isotropic region in the two‐component systems had a water content of up to 18% at 25°C. Solvents such as propylene glycol (PG), glycerol formal (FG), and ethyl alcohol increased the isotropic region. The area of isotropic region in these three‐component systems increased with increasing temperature. The area of the isotropic region became larger with decreasing dielectric constant and solubility parameter of the series of short‐chain alcohols, except n‐butyl alcohol, at 25°C. The systems exhibited Newtonian behavior. The solubility of both hydrophilic and lipophilic drugs was high in formulations at 25°C. It was concluded that more water was solubilized in MCMDG/short‐chain alcohols/water systems, and the isotropic region in the short‐chain alcohol systems enlarged compared with MCMDG/PG/water or MCMDG/GF/water systems, except the n‐butyl alcohol system. Hydrophilic and lipophilic drugs solubilize in the systems. The isotropic formulations containing MCMDG may represent an alternative to more traditional formulations for injectable formulations containing both lipophilic and hydrophilic drugs.