Complex Formation between Cationic Surfactants and Insoluble Drugs

Abstract

Abstract Water-insoluble drugs, 1-(2,4,6-trihydroxyphenyl)-1-propanone (flopropione) and 4-chloro-m-cresol, formed crystalline complexes with cationic surfactants, such as hexadecyl-, tetradecyl-, dodecyl-, and decyltrimethylammonium bromides, in a solubilized solution system when the solutions were kept at temperatures lower than 288 K and the solubilities of the crystalline complexes were significantly greater than those of only the drugs. Moreover, the complex crystals were more thermostable than only the drugs. The crystal structures of three complexes (4-chloro-m-cresol and hexadecyltrimethylammonium bromide (I), flopropione and tetradecyltrimethylammonium bromide (II), and flopropione and hexadecyltrimethylammonium bromide (III)) were analyzed by the X-ray diffraction method. These complexes were composed of the surfactant and drug molecules in a ratio of 1 : 1 (III) or 2 : 1 (I or II). In each crystal, the drug molecule was sandwiched by the alkyl chains of the surfactant molecules; the hydroxy group of the drug made a hydrogen bond with the bromide anion. Those structural characteristics were similar to those of the complexes between the surfactants and aromatic compounds. Such intermolecular interactions were responsible for the increased solubility and thermal stability of the complex.