The development of printable hydrogel inks for extrusion-based 3D printing is opening new possibilities to the production of new and/or improved pharmaceutical forms, specifically for topical application. Alginate and starch are natural polysaccharides that have been extensively exploited due to their biocompatibility, biodegradability, viscosity properties, low toxicity, and relatively low cost. This research work aimed to study the physicochemical and release kinetic effects of starch incorporation in alginate-based 3D hydrogel patches for topical delivery using a quality by design approach. The incorporation of a pregelatinized starch is also proposed as a way to improve the properties of the drug delivery system while maintaining the desired quality characteristics. Critical material attributes and process parameters were identified, and the sensitivity and adequacy of each parameter were statistically analyzed. The impact of alginate, starch, and CaCl₂·2H₂O amounts on relevant quality attributes was estimated crosswise. The amount of starch revealed a synergetic impact on porosity (p = 0.0021). An evident increase in the size and quantity of open pores were detected in the as printed patches as well as after crosslinking (15.6 ± 5.2 µm). In vitro drug release studies from the optimized alginate-starch 3D hydrogel patch, using the probe Rhodamine B, showed an initial high burst release, followed by a controlled release mechanism. The results obtained also showed that the viscoelastic properties, printing accuracy, gelation time, microstructure, and release rates can be modulated by varying the amount of starch added to the system. Furthermore, these results can be considered an excellent baseline for future drug release modulation strategies.

中文翻译：

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淀粉掺入对用于局部递送的基于藻酸盐的3D水凝胶贴剂的理化性质和释放动力学的影响。

用于基于挤出的3D打印的可印刷水凝胶油墨的开发为生产新的和/或改进的药物形式（特别是局部应用）开辟了新的可能性。海藻酸盐和淀粉是天然多糖，由于其生物相容性，生物降解性，粘度特性，低毒性和相对较低的成本而被广泛开发。这项研究工作旨在研究质量纳入设计方法的基于藻酸盐的3D水凝胶贴剂中淀粉掺入的物理化学和释放动力学效应，以进行局部递送。还提出了预糊化淀粉的掺入作为改善药物递送系统的性质同时保持所需质量特性的方法。确定了关键的材料属性和工艺参数，并对每个参数的敏感性和充分性进行统计分析。海藻酸盐，淀粉和氯化钙的影响对相关质量属性的₂ ·2H ₂ O量进行了交叉估计。淀粉的量显示出对孔隙率的协同作用（p = 0.0021）。在印刷中检测到开孔的大小和数量明显增加。以及交联后（15.6±5.2 µm）。使用罗丹明B探针从优化的藻酸盐-淀粉3D水凝胶贴剂进行的体外药物释放研究显示，初始高突发释放，然后是受控释放机制。获得的结果还表明，可以通过改变添加到体系中的淀粉的量来调节粘弹性，印刷精度，胶凝时间，微结构和释放速率。此外，这些结果可被视为未来药物释放调节策略的极佳基线。