title: Preparation and characterisation of hexamidine salts.
abstract: Hexamidine diisethionate (HEX D) has been used in the personal care industry and in a number of over-the-counter (OTC) drug products as an antimicrobial agent since the 1950's. Recently, the compound has also been investigated for its beneficial effects on skin health. Surprisingly, there is only limited information describing the physicochemical properties of this compound in the literature. The objective of this work was therefore to conduct a comprehensive programme of characterisation of HEX D as well as its dihydrochloride salt (HEX H). HEX H was prepared from HEX D by a simple acid addition reaction. Both salts were characterised using Nuclear Magnetic Resonance (NMR), Differential scanning calorimetry (DSC), and Thermogravimetric analysis (TGA). A new high performance liquid chromatographic method was developed and validated for both compounds. The pH in aqueous solution as well as respective distribution coefficients between octanol and pH 7.4 buffer were also determined. Finally, solubility and short term stability studies were conducted in a range of solvents. NMR analysis confirmed the preparation of HEX H from HEX D. Thermal analysis indicated the melting points of HEX D and HEX H were 225°C and 266°C respectively. HPLC analysis confirmed the purity of both salts. LogD values at pH 7.4 were -0.74 for HEX D and -0.70 for HEX H respectively. The physicochemical properties of two HEX salts have been established using a range of analytical approaches. Detailed solubility and stability data have also been collated. This information will be useful in the design of novel formulations for targeted delivery of these compounds to the skin.
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Parisi
authors.affiliation: Procter & Gamble Technical Centres Ltd., London Innovation Centre, Whitehall Lane, Egham, Surrey TW20 9NW, United Kingdom.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Matts
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lever
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hadgraft
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. Electronic address: majella.lane@btinternet.com.
authors.forename: Majella E
authors.initials: ME
authors.lastname: Lane
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D001550:Benzamidines / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008970:Molecular Weight; D012492:Salts / Q000737:chemistry; D012995:Solubility; D044366:Transition Temperature
chemical_list: D000890:Anti-Infective Agents; D001550:Benzamidines; D012492:Salts; C018961:hexamidine
keywords: Characterisation; Delivery; Hexamidine; Pre-formulation; Preparation; Salts