Journal of Chromatography A, 1195 (2008) 146–149 Contents lists available at ScienceDirect Journal of Chromatography A journal homepage: www.elsevier.com/locate/chroma New procedure for the determination of Hansen solubility parameters by means of inverse gas chromatography K. Adamska a, , R. Bellinghausen b , A. Voelkel a a Pozna´ n University of Technology, Institute of Chemical Technology and Engineering, pl. M. Sklodowskiej-Curie 2, 60-965 Pozna´ n, Poland b Bayer Technology Services GmbH, BTS-PT-PT – Product Design & Solid Processing, D-51368 Leverkusen, Germany article info Article history: Received 6 February 2008 Received in revised form 30 April 2008 Accepted 8 May 2008 Available online 14 May 2008 Keywords: Hansen solubility parameters Inverse gas chromatography Interaction coefficient Pharmaceutical excipients abstract The Hansen solubility parameter (HSP) seems to be a useful tool for the thermodynamic characteriza- tion of different materials. Unfortunately, estimation of the HSP values can cause some problems. In this work different procedures by using inverse gas chromatography have been presented for calculation of pharmaceutical excipients’ solubility parameter. The new procedure proposed, based on the Lindvig et al. methodology, where experimental data of Flory–Huggins interaction parameter are used, can be a rea- sonable alternative for the estimation of HSP values. The advantage of this method is that the values of Flory–Huggins interaction parameter for all test solutes are used for further calculation, thus diverse interactions between test solute and material are taken into consideration. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Solubility parameter determined for different materials can be used for estimating various physicochemical parameters, e.g. surface free energy, surface tension [1]. The solubility parameter concept has also been used to estimate the miscibility of different species [2]. Two materials having close values of solubility parame- ter are likely to be compatible and should be miscible when mixed together. Thus, solubility parameter has been used in coating indus- try for selection of solvents in paint formulation [3,4] or matching a binder to pigment [5], in printing industry for selection of the best cleaning agent for binder(s) [6] as well as for characterization of different additives (plasticizers, antistatic agents) used in polymers [7]. The concept of the solubility parameter was proposed by Scatchard et al. and initially applied to systems whose cohesion arises only from dispersion forces. This solubility parameter is the square root of cohesive energy density (CED) [8]. ı = (CED) 1/2 = H - RT V m 1/2 = E V m 1/2 (1) where ı = solubility parameter, R = gas constant, T = temperature, H = enthalpy of vaporization, V m = molar volume and E = energy of vaporization. Corresponding author. Tel.: +48 608 55 17 99; fax: +48 61 665 36 49. E-mail address: kaska.adamska@wp.pl (K. Adamska). For low- or non-volatile compounds it is impossible. There- fore, different methods were elaborated to facilitate the estimation of solubility parameter for this group of materials. These were: swelling measurements [9], group additive methods [10–12], where knowledge of the molecular structure of a material is required; viscosity measurements [13,14] and inverse gas chro- matography (IGC) [15–20]. Hansen introduced three dimensional solubility parameter or the Hansen solubility parameters (HSP) [21]. According to the Hansen theory, the cohesive energy can be considered as a sum of contributions from dispersive (E d ), polar (E p ) and hydrogen bond- ing (E h ) interactions: -E coh =-E d - E p - E h (2) and the total solubility parameter (ı T ) is expressed as ı 2 T = ı 2 d + ı 2 p + ı 2 h (3) where ı p , ı p , ı h denote dispersive, polar and hydrogen bonding contribution, respectively. Hansen solubility parameters could be determined by, e.g. solu- bility measurement and fit of data. A number of solvents are chosen in which the new substance with unknown Hansen parameters is solved and the solubility is measured. Depending on the sub- stances the fraction of the dissolved substance is determined by HPLC (actives, solids), GC (surfactants, solvents) or by balance mea- surements (solids/high boiling substances in volatile solvents) [21]. The solubility data are used to calculate the stability radius which define a sphere around the solvents in the Hansen “room”. The 0021-9673/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.chroma.2008.05.020