Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Department of Pharmacy, East Jeddah Hospital, Ministry of Health, Jeddah 22253, Saudi Arabia.
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
Eur J Pharm Biopharm. 2022 Aug;177:211-223. doi: 10.1016/j.ejpb.2022.07.003. Epub 2022 Jul 11.
Fixed-dose combinations (FDCs) achieve optimal goals for treatment with minimal side effects, decreased administration of large number of tablets, thus, greater convenience, and improved patient compliance. However, conventional FDCs do not have a guaranteed place in the future of patient-centered drug development because of the difficulty in achieving dose titration of each drug for individualized specific health needs and desired therapeutic outcomes. In the current study, FDCs of two antihypertensive drugs were fabricated with two distinct compartments using fused deposition modeling three-dimensional printing (FDM-3DP). Atorvastatin calcium and Amlodipine besylate loaded filaments were prepared by hot-melt extrusion. Shell-core FDC tablets were designed to have different infills for individualized dosing. Differential scanning calorimetry and powder X-ray diffraction revealed that both drugs were transformed into amorphous forms within the polymeric carriers. The fabricated tablets met the United States Pharmacopeia acceptance criteria for friability, content uniformity, and dissolution testing. The fabricated tablets were stable at room temperature with respect to drug content and thermal behavior over six months. This dynamic dosage form provides flexibility in dose titration and maintains the advantages of FDCs, thus achieving optimal therapeutic outcomes in different healthcare facilities.
固定剂量复方制剂（FDCs）以最小的副作用实现最佳的治疗目标，减少了大量片剂的服用，因此更加方便，提高了患者的依从性。然而，由于难以针对个体特定的健康需求和期望的治疗效果实现每种药物的剂量滴定，传统的 FDC 在以患者为中心的药物开发的未来中并没有一个确定的位置。在本研究中，使用熔融沉积建模三维打印（FDM-3DP）技术，用两种不同的隔室制造了两种降压药物的 FDC。阿托伐他汀钙和氨氯地平贝那普利负载长丝通过热熔挤出法制备。壳核 FDC 片剂设计为具有不同的填充，以实现个体化给药。差示扫描量热法和粉末 X 射线衍射表明，两种药物都在聚合物载体中转化为无定形形式。所制备的片剂符合美国药典关于脆碎度、含量均匀度和溶出度测试的接受标准。在六个月的时间里，所制备的片剂在室温下的药物含量和热行为方面均稳定。这种动态剂型在剂量滴定方面具有灵活性，并保持了 FDC 的优势，从而在不同的医疗机构实现最佳的治疗效果。
