Relationship between swelling of hydroxypropylmethylcellulose and the Hansen and Karger partial solubility parameters

Abstract

A model that relates the equilibrium swelling of hydroxypropylmethylcellulose to the partial solubility parameters of both the polymer and the solvents is proposed to interpret and correlate the experimental data. The non-specific interactions are expressed as the dispersion δd and polar δp solubility parameters of Hansen, or as a combination of both. Hydrogen bonding is represented by the acidic δa and the basic δb Karger solubility parameters. The results are compared with models including the same parameters for non-specific interactions (δd and δp) and the Hansen hydrogen bonding parameter δh. Equilibrium swelling of this hydrophilic polymer that is widely used in drug formulation is measured in pure solvents covering a wide polarity range. In a qualitative way, swelling increases in solvents with higher Hildebrand solubility parameters and stronger hydrogen bonding capability, and it decreases in non-polar solvents. Single polarity indexes, such as the Hildebrand solubility parameter or the partition coefficient (PC), do not fit well the overall experimental data. The best correlations were obtained with the proposed model, providing at the same time an interpretation consistent with the physical meaning of the terms included in the equation. Swelling increases as the non-specific interactions of the polymer and the solvents become alike, and as the Lewis acid-base interactions of the polymer (1) and the solvent (2) represented by the products δ1aδ2b and δ1bδ2a become greater. Conversely, hydrogen bonding self association of the solvents (the product δ1aδ1b) lowers swelling. The results show that the Karger hydrogen bonding parameters provide a better approach than the Hansen hydrogen bonding parameter to correlate the swelling behavior of a hydrophilic polymer. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association.