Merck

Preparation and characterisation of hexamidine salts.

International journal of pharmaceutics (2015-08-04)
Nicola Parisi, Paul J Matts, Rebecca Lever, Jonathan Hadgraft, Majella E Lane
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Lysine monohydrochloride, reagent grade, ≥98% (HPLC)
Sigma-Aldrich
L-Lysine monohydrochloride, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
2-Propanol, BioReagent, for molecular biology, ≥99.5%
Sigma-Aldrich
Oleic acid, suitable for cell culture, BioReagent
Sigma-Aldrich
1,2-Propanediol, meets analytical specification of Ph. Eur., BP, USP, ≥99.5%
Sigma-Aldrich
2-Propanol, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
L-Lysine monohydrochloride, BioUltra, ≥99.5% (AT)
Sigma-Aldrich
1,2-Propanediol, puriss. p.a., ACS reagent, ≥99.5% (GC)
Sigma-Aldrich
Oleic acid, meets analytical specification of Ph, Eur., 65.0-88.0% (GC)
Sigma-Aldrich
Acetonitrile, for DNA synthesis
Sigma-Aldrich
Hexarelin, ≥90% (HPLC)
Sigma-Aldrich
Methanol-12C, 99.95 atom % 12C
Sigma-Aldrich
Glycerol, FCC, FG
Sigma-Aldrich
2-Ethylhexyl salicylate, ≥99%
Sigma-Aldrich
Oleic acid, technical grade, 90%
Sigma-Aldrich
Glycerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)
Sigma-Aldrich
Glycerol, for molecular biology, ≥99.0%
Sigma-Aldrich
Glycerol, BioXtra, ≥99% (GC)
Sigma-Aldrich
Glycerol, ≥99.5%
Sigma-Aldrich
Oleic acid, ≥99% (GC)
Sigma-Aldrich
2-Ethylhexyl salicylate, 99%
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Sigma-Aldrich
Glycerol, BioUltra, for molecular biology, anhydrous, ≥99.5% (GC)
Sigma-Aldrich
1,3-Propanediol, 98%
Sigma-Aldrich
2-Propanol, anhydrous, 99.5%
Sigma-Aldrich
Oleic acid, natural, FCC
Sigma-Aldrich
1,2-Propanediol, ACS reagent, ≥99.5%
Sigma-Aldrich
1,2-Propanediol, ReagentPlus®, 99%
Sigma-Aldrich
2-Propanol, electronic grade, 99.999% trace metals basis
Sigma-Aldrich
Acetonitrile, electronic grade, 99.999% trace metals basis