Thermosensitive Hydrogels as crystallization media

crystallization in a gel matrix represents an interesting alternative to solution crystallization, producing crystals with a narrow particle size distribution, regular shape and smooth surface. The origin of this technique goes back to the end of 1800, when the German chemist and photographer Liesegang observed precipitation of salts in gelatin[2]. The technique has been popular in the 60-70 as an easier way in order to obtain perfect, defect free crystalline substances[3]. The gel crystallization has been object of a large number of publications up to the 80, well reviewed by Arora[3], much of them focused on the investigation of the crystals growth mechanism or on the effect of the variables involved. A problem concerning this technique is the procedure for the crystals recovery, which is usually obtained through manually removal of each single crystals, as suggested by Robert [4]. A solution of the problem has been proposed by Zeng, through the use of a pH reversible gel system. This work focus on the use of a thermoreversible gel system able to work as a crystallization media. The gel system is composed by a water dispersion of poloxamer 407, characterized by a temperature dependent behaviour while the model substance for the crystallization process is represented by lactose. In a previously work [] the system water-poloxamer-lactose has been reologically analysed in order to individuate the concentration range able to assure a gel point around 16-20°C. In this work the crystallization system and the quality of the crystal produced are evaluated. Systems water-poloxamer-lactose resulted unsatisfactory due to the poor yield of the process, so part of the water has been substituted with ethanol in order to decrease the lactose solubility (increasing the system supersaturation) without altering the gel point. The crystallization system was left in the incubator at controlled temperature (around 2°C over the gel point) and the crystals recovered filtrating the ungelled solutions obtaind by cooling of the gel system. The recovered crystals were analysed through calorimetry and optical microscopy and compared with the starting materials and with crystals prepared by simply crystallization. DSC results showed as the crystals prepared by gel crystallization are constitute only by-lactose monohydrate without trace of other lactose polymorph of amorph forms, as in the case of the control crystals. The analysis of the crystals through microscopy showed as the materials prepared by gel crystallization is constituted by bigger crystals, with a perfect geometry, smooth and defect free surface, narrow particle size distribution compared with the control crystals or the starting materials. This results suggest as the gel crystallization carried out using a thermoreversible gel based on poloxamer 407 is a performing crystallization system able to generate high quality crystals.