M Tawfeek Hesham, Hassan Yasser A, Aldawsari Mohammed F, H Fayed Mohamed
Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 35523, Egypt.
Pharmaceuticals (Basel). 2020 Dec 5;13(12):446. doi: 10.3390/ph13120446.
Sulpiride (SUL) is a dopamine D-receptor antagonist used for management of GIT disturbance and it has anti-psychotic activities based on the administered dose. SUL undergoes P-glycoprotein efflux, which lead to poor bioavailability and erratic absorption. Therefore, the objective of this research was an attempt to enhance the oral bioavailability of SUL via formulation of fast disintegrating tablets (SUL-FDTs) with a rapid onset of action. A 3 full-factorial design was performed for optimization of SUL-FDTs using desirability function. The concentration of superdisintegrant (X) and Prosolv (X) were selected as independent formulation variables for the preparation and optimization of SUL-FDTs using direct compression technique. The prepared SUL-FDTs were investigated regarding their mechanical strength, disintegration time, drug release and in vivo pharmacokinetic analysis in rabbits. The optimized formulation has hardness of 4.58 ± 0.52 KP, friability of 0.73 ± 0.158%, disintegration time of 37.5 ± 1.87 s and drug release of 100.51 ± 1.34% after 30 min. In addition, the optimized SUL-FDTs showed a significant ( < 0.01) increase in C and AUC() and a relative bioavailability of about 9.3 fold compared to the commercial product. It could be concluded that SUL-FDTs are a promising formulation for enhancing the oral bioavailability of SUL concomitant with a fast action.
舒必利（SUL）是一种多巴胺D受体拮抗剂，用于治疗胃肠道紊乱，根据给药剂量具有抗精神病活性。SUL会经历P-糖蛋白外排，这导致生物利用度低和吸收不稳定。因此，本研究的目的是尝试通过制备起效迅速的快速崩解片（SUL-FDTs）来提高SUL的口服生物利用度。采用期望函数对SUL-FDTs进行优化，进行了三因素全因子设计。选择超级崩解剂（X）和Prosolv（X）的浓度作为独立的处方变量，采用直接压片技术制备和优化SUL-FDTs。对制备的SUL-FDTs进行了机械强度、崩解时间、药物释放和家兔体内药代动力学分析。优化后的制剂硬度为4.58±0.52 KP，脆碎度为0.73±0.158%，崩解时间为37.5±1.87 s，30分钟后药物释放率为100.51±1.34%。此外，优化后的SUL-FDTs的C和AUC（）显著增加（<0.01），与市售产品相比相对生物利用度约为9.3倍。可以得出结论，SUL-FDTs是一种有前途的制剂，可提高SUL的口服生物利用度并伴随快速起效。
