Locally Acting Budesonide-Loaded Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS) for Distal Ulcerative Colitis

Hany SM Ali,1,2 Ahmed F Hanafy,3 Rawan Bafail,1 Hamad Alrbyawi,1 Marey Almaghrabi,1 Yaser M Alahmadi,4 Samar El Achy5 1Department of Pharmaceutics and Pharmaceutical Industries, College of Pharmacy, Taibah University, Madinah, Al-Madinah Al-Munawwarah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt; 3Research and Development Department, Al Andalous Pharmaceutical Industries, Giza, Egypt; 4Department of Pharmacy Practice, College of Pharmacy, Taibah University, Madinah, Al-Madinah Al-Munawarah, 30001, Saudi Arabia; 5Department of Anatomical Pathology, Faculty of Medicine, University of Alexandria, Alexandria, EgyptCorrespondence: Hany SM Ali, Email hsali@taibahu.edu.sa, hafandy2000@yahoo.comBackground: Budesonide (BUD) is a BCS class II medication with poor water solubility and limited oral bioavailability. In this study, innovative solid self-microemulsifying drug delivery systems (BUD-SMEDDS) were developed for effective local management of distal ulcerative colitis (UC).Methods: Based on solubility and emulsification tests, the components of the self-microemulsifying drug delivery system (SMEDDS) were Capryol™ 90, Tween 80, and Transcutol HP. The impacts of BUD-SMEDDS ingredients (as inputs) on the average globule size (AGS), polydispersity index (PDI), and self-emulsification time (SET) as responses were investigated using the Box–Behnken design methodology. Solid rectal systems were then fabricated using the optimized values of SMEDDS components in Lutrol® bases. The developed systems were evaluated for in vitro characteristics and in vivo efficacy using a rat colitis model.Results: For all responses, the greatest impact was attributed to the oil content of SMEDDS. An optimized BUD-SMEDDS with AGS of 33 ± 2.9 nm, PDI of 0.29 ± 0.03 and SET of 25 ± 2.5 s) was selected for rectal formulations. The developed formulations demonstrated acceptable physical characteristics and mucoadhesive abilities. Differential scanning calorimetric (DSC) analysis revealed the absence of BUD crystallinity in the SMEDDS formulations. The drug release patterns could be regulated by selecting the grade and composition of the incorporated Lutrols. Clinical and histopathological assessments revealed considerable improvements in animals treated with BUD-SMEDDS formulations.Conclusion: Overall findings confirmed the superior capability of solid SMEDDS as BUD carriers to manage distal colitis in tested animals.Keywords: Budesonide, SMEDDS, Ulcerative colitis, Box Behnken design, efficacy