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.

中文翻译：

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海藻酸盐颗粒离子交联过程中西地那非的原位结晶

研究了含有药物晶体的水凝胶颗粒，以开发具有改进的可加工性、生物利用度和物理稳定性的药物制剂。然而，由于制备过程及其控制中涉及的各种困难，水凝胶颗粒内部的晶体工程受到限制。该研究通过使用一种简单且可扩展的制备技术证明了海藻酸盐颗粒的交联和颗粒内药物西地那非的同时结晶。药物晶体的粒径成功地降低到亚微米范围，而它们的结晶度可以通过加工参数控制。此外，这些结果被证明是由于聚合物链和药物之间的强相互作用以及溶剂的扩散限制过程，抗溶剂、西地那非、藻酸盐和交联离子 (Ca2+)。这种简单的结晶技术将有助于开发基于水凝胶和药物微晶的新型药物递送系统。