Rheologic and NMR characterization of monoglyceride-based formulations

Abstract

This paper describes the production and characterization of semi-solid formulations based on monoglycerides from canola oil and water as drug-delivery systems. In order to obtain new formulations with different characteristics in terms of viscosity, bioadhesiveness, and solubilization capacity, a third component was added to the monoglyceride-water system. Nine excipients were tested, namely soy oil, isopropylmyristate, isopropylpalmitate, tripalmitin, tristearin, glyceryl monostearate, glycerol, propylene glycol, and ethanol. In particular, the effect of each excipient on the viscosity and stability of the formulation was investigated. It was found that ethanol dramatically influenced the viscosity of the monoglyceride-water system, resulting in the formation of stable forms. In addition, ethanol suitably could be used for the solubilization of water-insoluble lipophilic drugs. This promising ternary system was characterized by microscopic, NMR spectroscopic, and rheologic techniques. (1)H and (13)C NMR studies were made of Myverol to verify the molecular structure and isomer distributions of this commercial monoacylglycerol mixture. The microstructure of an isotropic solution consisting of Myverol [1.8% (w/w)], ethanol (42.9%), and water (55.3%) was studied by the multi-component self-diffusion NMR method. From the self-diffusion coefficient (D) of the monoglycerides (8.8 x 10-11 m(2)/s), an "apparent spherical hydrodynamic radius" of ca. 2.48 nm was calculated for the micellar aggregate. A nearly spherical shape is consistent with these values since the extended hydrocarbon chain of the longest monoglyceride (17 carbons) is ca. 2.2 nm long. The D's of water and ethanol reveal they do not associate (no attractive nonbonding interactions) appreciably with the fatty acid micelles.