Tawfeek Hesham M, Abdellatif Ahmed A H, Dennison Thomas J, Mohammed Afzal R, Sadiq Younis, Saleem Imran Y
Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt; Department of Pharmaceutics, Faculty of Pharmacy, Qassim University, Buraydah, Saudi Arabia.
Int J Pharm. 2017 Oct 5;531(1):80-89. doi: 10.1016/j.ijpharm.2017.08.069. Epub 2017 Aug 15.
The aim of this work was to investigate the efficient targeting and delivery of indometacin (IND), as a model anti-inflammatory drug to the colon for treatment of inflammatory bowel disease. We prepared fast disintegrating tablets (FDT) containing IND encapsulated within poly(glycerol-adipate-co-ɷ-pentadecalactone), PGA-co-PDL, microparticles and coated with Eudragit L100-55 at different ratios (1:1.5, 1:1, 1:0.5). Microparticles encapsulated with IND were prepared using an o/w single emulsion solvent evaporation technique and coated with Eudragit L-100-55 via spray drying. The produced coated microparticles (PGA-co-PDL-IND/Eudragit) were formulated into optimised FTD using a single station press. The loading, in vitro release, permeability and transport of IND from PGA-co-PDL-IND/Eudragit microparticles was studied in Caco-2 cell lines. IND was efficiently encapsulated (570.15±4.2μg/mg) within the PGA-co-PDL microparticles. In vitro release of PGA-co-PDL-IND/Eudragit microparticles (1:1.5) showed significantly (p<0.05, ANOVA/Tukey) lower release of IND 13.70±1.6 and 56.46±3.8% compared with 1:1 (89.61±2.5, 80.13±2.6%) and 1:0.5 (39.46±0.9 & 43.38±3.12) after 3 and 43h at pH 5.5 and 6.8, respectively. The permeability and transport studies indicated IND released from PGA-co-PDL-IND/Eudragit microparticles had a lower permeability coefficient of 13.95±0.68×10cm/s compared to free IND 23.06±3.56×10cm/s. These results indicate the possibility of targeting anti-inflammatory drugs to the colon using FDTs containing microparticles coated with Eudragit.
本研究旨在探讨将作为模型抗炎药物的吲哚美辛（IND）有效靶向递送至结肠以治疗炎症性肠病。我们制备了快速崩解片（FDT），其包含包裹在聚（甘油己二酸酯 - 共 - ω - 十五内酯）（PGA - co - PDL）微粒中的IND，并以不同比例（1:1.5、1:1、1:0.5）用尤特奇L100 - 55包衣。采用水包油单乳液溶剂蒸发技术制备包裹IND的微粒，并通过喷雾干燥用尤特奇L - 100 - 55包衣。将制备的包衣微粒（PGA - co - PDL - IND/尤特奇）使用单冲压片机配制成优化的FTD。在Caco - 2细胞系中研究了IND从PGA - co - PDL - IND/尤特奇微粒中的载药量、体外释放、渗透性和转运情况。IND被有效地包裹在PGA - co - PDL微粒中（570.15±4.2μg/mg）。PGA - co - PDL - IND/尤特奇微粒（1:1.5）的体外释放在pH 5.5和6.8条件下3小时和43小时后，与1:1（89.61±2.5，80.13±2.6%）和1:0.5（39.46±0.9 & 43.38±3.12）相比，IND的释放量显著较低（p<0.05，方差分析/ Tukey检验），分别为13.70±1.6和56.46±3.8%。渗透性和转运研究表明，与游离IND 23.06±3.56×10cm/s相比，从PGA - co - PDL - IND/尤特奇微粒中释放的IND的渗透系数较低，为13.95±0.68×10cm/s。这些结果表明，使用含有用尤特奇包衣微粒的FDT将抗炎药物靶向递送至结肠是有可能的。
