In-situ crystallization of sildenafil during ionic crosslinking of alginate granules

Hydrogel particles containing drug crystals were investigated for the development of drug formulations with improved processability, bioavailability, and physical stability. However, crystal engineering inside hydrogel particles has been limited due to various difficulties involved in the preparation processes and their control. This study demonstrates the crosslinking of alginate granules and the simultaneous crystallization of a drug, sildenafil, inside the granules by using a simple and scalable preparation technique. The particle size of the drug crystals was successfully decreased to the submicron range while their crystallinity could be controlled by the processing parameters. Moreover, these results are shown to be due to the strong interactions between the polymer chains and the drug as well as the diffusion-limited processes of solvent, antisolvent, sildenafil, alginate, and crosslinking ions (Ca²⁺). This simple crystallization technique will be useful for the development of novel drug delivery systems based on hydrogels and drug crystallites.