Characterization of oleic acid and propranolol oleate mesomorphism using C-13 solid-state nuclear magnetic resonance spectroscopy (SSNMR)

Lipids regularly exhibit complicated thermotropic and lyotropic phase behav ior. In this study, the utility of C-13 solid-state nuclear magnetic resona nce spectroscopy (SSNMR) in characterizing the phase properties of pharmace utical lipids was investigated. Variable temperature C-13 SSNMR spectra and spin-lattice relaxation times (T-1(C)) were obtained for high-purity oleic acid (OA) and propranolol oleate (POA). Spectral changes took place follow ing OA gamma-to-alpha phase transition that indicated increased nuclear ine quivalence of aliphatic chain carbons in the alpha phase. T-1(C) data for t he or phase demonstrated considerable conformational changes throughout the aliphatic chain, not solely in the methyl side chain as previously reporte d. These data support alpha-OA classification as a conformationally disorde red crystalline phase. The prevalence of low T-1(C) values in both POA I an d II suggested the absence of a rigid crystalline molecular lattice, so bot h phases were described as conformationally disordered crystalline phases. A two-phase mixture of POA I and II was also identified, emphasizing the se nsitivity of this technique. C-13 SSNMR provided valuable information regar ding the nuclear environment of specific functional groups in lipid crystal line and mesomorphic structures. Understanding phase behavior at the molecu lar level can aid selection of appropriate formulation strategies for lipid s by allowing prediction of processing properties, and physical and chemica l stability. C-13 SSNMR is a powerful technique for pharmaceutical lipid ch aracterization. (C) 2000 Wiley-Liss, Inc. and the American Pharmaceutical A ssociation.