Oleate salt formation and mesomorphic behavior in the propranolol oleic acid binary system

Thermal analysis of propranolol/oleic acid mixtures prepared by solvent eva poration enabled construction of the binary system phase diagram. This allo wed both physical and chemical interactions to be identified, including com plex formation at the equimolar composition. An incongruent melting complex with a characteristic reaction point was identified in excess oleic acid c ompositions; a common property of fatty acid/fatty acid salt binary systems . The equimolar complex was confirmed to be propranolol oleate using infrar ed spectroscopy. Wide-angle X-ray powder diffractometry demonstrated that p ropranolol oleate possessed long-range positional order (similar to 25 Angs trom d spacing) accompanied by a degree of disorder over shorter d spacings . Such a pattern suggested mesophase formation, explaining the unctuous nat ure of propranolol oleate at room temperature. Accurate measurement of the long-range d spacing was achieved using small-angle X-ray scattering, permi tting differentiation of the three different phases identified (phase I: 25 .4 Angstrom, phase II: 24.6 Angstrom phase III: 25.4-25.5 Angstrom). The im plications of drug fatty acid salt formation and also mesomorphism in pharm aceutical systems are discussed.