Enhanced microemulsion formation in lipid-based drug delivery systems by combining mono-esters of mediumchain fatty acids with di- or tri-esters

Abstract

To develop strategies for selecting appropriate lipids from mono-, di- and tri-esters of medium-chain fatty acids for the development of lipid-based drug delivery systems, ternary phase diagrams of propylene glycol (PG) monocaprylate (Capryol® 90; HLB~7), PG dicaprylocaprate (Labrafac™ PG; HLB~2) and glycerol tricaprylocaprate (Labrafac™ Lipophile WL1349; HLB~2) were determined in combination with a common surfactant, PEG-35 castor oil (Cremophor® EL, HLB~13), and water. Particle size and viscosity in different regions of the phase diagrams were measured, solubility of a model drug, danazol, in different lipid-surfactant mixtures was determined, and dispersion testing by diluting selected preconcentrates with 250 ml 0.01 NHCl was performed. Further, phase diagrams were constructed using binary mixtures of lipids (monoester with diester, or monoester with triester) in place of single lipids. The phase diagrams of PG dicaprylocaprate and glycerol tricaprylocaprate were similar, while it was distinctly different for PG monocaprylate. The microemulsion regions in phase diagrams were rather limited for individual lipids, and additionally, the diand tri-esters showed pronounced gel regions in the phase diagrams, which could influence drug release from preconcentrates. The mixing of PG monocaprylate (monoester) with PG dicaprylocaprate (diester) or glycerol tricaprylocaprate (triester) had dramatic effects on the performance of lipids as evidenced by the greatly reduced gel phases, much larger microemulsion regions, faster dispersion of the preconcentrates in an aqueous medium, and smaller particle size of the microemulsions subsequently formed.