Low viscosity monoglyceride-based drug delivery systems transforming into a highly viscous cubic phase

Abstract

A highly viscous, but not injectable, cubic phase with sustained drug release properties forms from unsaturated monoglycerides (glycerol monooleate or monolinoleate) in contact with aqueous media. In order to obtain a flowable, injectable system, low viscosity monoglyceride-based formulations (lamellar phase, isotropic solution phase or hexagonal phase), which transform into the cubic phase after contact with dissolution fluids, were developed. The addition of either drugs (drug-induced) or organic solvents (solvent-induced) to the monoglyceride–water system resulted in low viscosity systems. Chlorpheniramine maleate (CPM) and propranolol (PPL) HCl were selected as model drugs for the drug-induced systems, and injectable solvents (e.g. ethanol, polyethylene glycol, propylene glycol, N-methyl-2-pyrrolidone) for the solvent-induced systems. Triangular phase diagrams were used to characterize the three-component mixtures, and the different mesophases were identified by polarized light microscopy. Various monoglyceride compositions with low viscosities were investigated in drug release studies, during which they transformed into the cubic phase. For the drug-induced low viscosity formulations, the drug release decreased with increasing monoglyceride content and decreasing drug content. In comparison, the release of PPL HCl from the ethanol-induced formulation was faster, but still sustained, when compared to the release from drug-induced formulation.