Rheologic and NMR characterization of monoglyceride-based formulations

This paper describes the production and characterization of semi-solid form ulations based on monoglycerides from canola oil and water as drug-delivery systems. In order to obtain new formulations with different characteristic s in terms of viscosity, bioadhesiveness, and solubilization capacity, a th ird component was added to the monoglyceride-water system. Nine excipients were tested, namely soy oil, isopropylmyristate, isopropylpalmitate, tripal mitin, tristearin, glyceryl monostearate, glycerol, propylene glycol, and e thanol. In particular, the effect of each excipient on the viscosity and st ability of the formulation was investigated. It was found that ethanol dram atically influenced the viscosity of the monoglyceride-water system, result ing in the formation of stable forms, in addition, ethanol suitably could b e used for the solubilization of water-insoluble lipophilic drugs. This pro mising ternary system was characterized by microscopic, NMR spectroscopic, and theologic techniques. H-1 and C-13 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 consi sting of Myverol [1.8% (w/w)], ethanol (42.9%), and water (55.3%) was studi ed by the multicomponent self-diffusion NMR method. From the self-diffusion coefficient (D) of the monoglycerides (8.8 x 10-11 m(2)/s), an "apparent s pherical hydrodynamic radius" of ca. 2.48 nm was calculated for the micella r aggregate. A nearly spherical shape is consistent with these values since the extended hydrocarbon chain of the longest monoglyceride (17 carbons) i s ca. 2.2 nm long. The D's of water and ethanol reveal they do not associat e (no attractive nonbonding interactions) appreciably with the fatty acid m icelles. (C) 2000 John Wiley & Sons, Inc.