The aim of this study was to investigate and compare the physical stability and solubility of the liquid crystalline form of fenoprofen calcium as pure drug and in a proprietary tablet formulation (Nalfon), and to investigate if a simple heat treatment of a proprietary tablet containing fenoprofen calcium may lead to a physically stable formulation with enhanced dissolution rate and apparent solubility. The liquid crystalline form of fenoprofen calcium (thermotropic mesophase) was prepared by heating the crystalline drug to 125 degrees C to remove the water of crystallisation. Differential scanning calorimetry investigation revealed an endothermic peak at 89 degrees C upon heating (liquid crystal formation) attributable to water loss from the crystalline dihydrate. The liquid crystalline order was maintained upon cooling. No interference of tablet excipients with the thermal behaviour of the drug in the tablet formulation was observed. The crystalline dihydrate and liquid crystalline forms of fenoprofen calcium could be differentiated by diffuse reflectance infra-red spectroscopy and X-ray powder diffraction, both as pure drug and in tablet formulation. The supercooled liquid crystal (thermotropic reversed hexagonal phase) alone and in preheated and ground tablets was physically stable when stored in a dry environment or at 33% relative humidities (RH) at both 20 and 40 degrees C for 2 months. At 40 degrees C and 75% RH the supercooled mesophase extensively converted to the crystalline dihydrate within 6 days. Liquid crystalline fenoprofen calcium stored at 20 degrees C and 75% RH showed only partial dihydrate conversion after 2 months of storage. The solubility of the crystalline dihydrate alone and from the tablet formulation was 2.8+/-0.2 mg/ml and 3.0+/-0.2 mg/ml (mean+/-s.d.), respectively, (not significantly different), whereas the maximum solubility of the liquid crystal was 5.0+/-0.3 mg/ml (mean+/-s.d.) and 6.9+/-0.6 mg/ml (mean+/-s.d.), respectively (significantly different). The difference in maximum solubility between the crystalline dihydrate form of fenoprofen calcium and the fenoprofen calcium mesophase was highly significant, for both the pure drugs and the tablet formulations. The dissolution rate of the liquid crystalline fenoprofen calcium in preheated, intact tablets was significantly lower than that of the crystalline form in non-preheated tablets. Gross visual changes and scanning electron microscopy indicated that the disintegration properties of the tablet may be detrimentally effected by heating the tablet to 125 degrees C, diminishing the beneficial effect of improved solubility of the liquid crystal. The study has shown that conversion of the crystalline form of fenoprofen calcium to the liquid crystal can enhance the apparent solubility of the pure drug and the drug in presence of tablet excipients, but that the conversion should be performed before tablet formulation in order to increase dissolution of this poorly water-soluble drug.