Aim: Etoricoxib is a selective inhibitor of COX-2 enzyme. It is proposed as a potent anti-inflammatory drug intended for the control of irritable bowel syndrome. The current work aimed at developing etoricoxib-loaded nanoparticles for colon- targeting.
Materials and Methods: PLGA nanoparticles were developed via nano-spray drying technique. The D-optimal design was adopted for the investigation of the influence of i) DL-lactide-coglycolide (PLGA) concentration, ii) polyvinylpyrrolidone K30 (PVP K30) concentration and iii) lactide:glycolide ratio in the copolymer chain on the yield%, the encapsulation efficiency (EE%), particle size (PS) and percentage of drug release after 2h (P_2h), 4h (P_4h) and 12h (P_12h). To promote colon targeting of the systems, the best achieved system (M14) was either directly coated with poly(methacrylic acid-co-methyl methacrylate) [Eudragit^®-S100] or loaded into hard gelatin capsules and the capsules were coated with poly(methacrylic acid-co-methyl methacrylate) (E-M14C). The pharmacokinetic parameters of etoricoxib following oral administration of E-M14C in healthy volunteers were assessed relative to commercial etoricoxib tablets.
Results: M14 system was prepared using PLGA (0.5% w/v) at a lactide:glycolide ratio of 100:0, in the presence of PVP K30 (2% w/v). M14 system was nano-spherical particles of 488 nm size possessing promising yield% (63.5%) and EE% (91.2%). The percentage drug released after 2, 4 and 12 hours were 43.41%, 47.34 and 64.96%, respectively. Following M14-loading into hard gelatin capsules and coating with poly(methacrylic acid-co-methyl methacrylate) [Eudragit-S100], the respective P_2h, P_4h and P_12h were 10.1%, 28.60% and 65.45%. Significant (p < 0.05) differences between the pharmacokinetic parameter of E-M14C in comparison with the commercial product were revealed with a delay in T_max (from 2.5h to 6h), a prolongation in MRT_0-∞ (from 24.4h to 34.7h) and an increase in the relative oral bioavailability (4.23 folds).
Conclusion: E-M14C is a potential system for possible colon targeting of etoricoxib.

Keywords: colon targeting, etoricoxib, nano spray drying, PLGA, Eudragit-S100


中文翻译：

---

Eudragit®-S100 包被的 PLGA 纳米颗粒用于依托考昔的结肠靶向：健康人类志愿者的优化和药代动力学评估。

目的：依托考昔是一种选择性COX-2酶抑制剂。它被提议作为一种有效的抗炎药，用于控制肠易激综合征。目前的工作旨在开发用于结肠靶向的载有依托考昔的纳米颗粒。
材料与方法： PLGA纳米粒子是通过纳米喷雾干燥技术开发的。采用 D 优化设计来研究 i) DL-丙交酯-共乙交酯 (PLGA) 浓度、ii) 聚乙烯吡咯烷酮 K30 (PVP K30) 浓度和 iii) 共聚物链中丙交酯:乙交酯比对产率的影响、2h (P _2h )、4h (P _4h )和12h (P _12h )后的包封率(EE%)、粒径(PS)和药物释放百分比）。为了促进系统的结肠靶向，获得最佳的系统 (M14) 直接涂有聚（甲基丙烯酸-共-甲基丙烯酸甲酯）[Eudragit ^® -S100] 或装入硬明胶胶囊中，胶囊涂有聚（甲基丙烯酸-共-甲基丙烯酸甲酯) (E-M14C)。相对于市售的依托考昔片剂，评估了健康志愿者口服 E-M14C 后依托考昔的药代动力学参数。
结果：在 PVP K30 (2% w/v) 存在下，使用 PLGA (0.5% w/v) 以 100:0 的丙交酯:乙交酯比率制备 M14 系统。M14体系是488 nm大小的纳米球形颗粒，具有良好的产率%（63.5%）和EE%（91.2%）。2、4和12小时后药物释放的百分比分别为43.41%、47.34和64.96%。在将 M14 装入硬明胶胶囊并用聚（甲基丙烯酸-共-甲基丙烯酸甲酯）[Eudragit-S100] 包衣后，P _2h、P _4h和 P _12h分别为 10.1%、28.60% 和 65.45%。与商业产品相比，E-M14C 的药代动力学参数存在显着差异( p < 0.05)，T _max延迟（从 2.5 小时到 6 小时），MRT _0-∞的延长（从 24.4 小时到 34.7 小时）和相对口服生物利用度的增加（4.23 倍）。
结论： E-M14C是依托考昔可能的结肠靶向系统。

关键词：结肠靶向，依托考昔，纳米喷雾干燥，PLGA，Eudragit-S100