title: Characterization of oleic acid and propranolol oleate mesomorphism using (13)C solid-state nuclear magnetic resonance spectroscopy (SSNMR).
abstract: Lipids regularly exhibit complicated thermotropic and lyotropic phase behavior. In this study, the utility of (13)C solid-state nuclear magnetic resonance spectroscopy (SSNMR) in characterizing the phase properties of pharmaceutical lipids was investigated. Variable temperature (13)C 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 following OA gamma-to-alpha phase transition that indicated increased nuclear inequivalence of aliphatic chain carbons in the alpha phase. T(1)(C) data for the alpha phase demonstrated considerable conformational changes throughout the aliphatic chain, not solely in the methyl side chain as previously reported. These data support alpha-OA classification as a conformationally disordered crystalline phase. The prevalence of low T(1)(C) values in both POA I and II suggested the absence of a rigid crystalline molecular lattice, so both phases were described as conformationally disordered crystalline phases. A two-phase mixture of POA I and II was also identified, emphasizing the sensitivity of this technique. (13)C SSNMR provided valuable information regarding the nuclear environment of specific functional groups in lipid crystalline and mesomorphic structures. Understanding phase behavior at the molecular level can aid selection of appropriate formulation strategies for lipids by allowing prediction of processing properties, and physical and chemical stability. (13)C SSNMR is a powerful technique for pharmaceutical lipid characterization.
authors.affiliation: Drug Delivery Group, Postgraduate Studies in Pharmaceutical Technology, University of Bradford, Bradford, BD7 1DP, United Kingdom.
authors.forename: K J
authors.initials: KJ
authors.lastname: Crowley
authors.forename: R T
authors.initials: RT
authors.lastname: Forbes
authors.forename: P
authors.initials: P
authors.lastname: York
authors.forename: D C
authors.initials: DC
authors.lastname: Apperley
authors.forename: H
authors.initials: H
authors.lastname: Nyqvist
authors.forename: O
authors.initials: O
authors.lastname: Camber
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000737:chemistry*; D002247:Carbon Isotopes; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008968:Molecular Conformation; D019301:Oleic Acid / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry*
chemical_list: D000319:Adrenergic beta-Antagonists; D002247:Carbon Isotopes; D008055:Lipids; D019301:Oleic Acid; D011433:Propranolol