Abstract
The purpose of this study was to apply the quality-by-design (QbD) approach for the development of colon-targeted curcumin-loaded polymeric microparticles (Col-CUR-MPs). The proportion of the enterosoluble polymer (Eudragit® FS) in the polymeric matrix, curcumin concentration, and the concentration of the polymer mixture (Eudragit® FS-polycaprolactone) were identified as potential risk factors for the quality of the final product following risk assessment. The influence of these variables on the critical quality attributes (CQAs) of Col-CUR-MPs was investigated. Therefore, a central composite face experimental design was used in order to determine the functional relationships between variables and product CQAs. The obtained regression model and contour plots were used to establish the design space. Finally, the model was validated by preparing two microparticulate formulations, one corresponding to the robust setpoint from within the design space and one outside the established design space, and calculating the percentage bias between the experimental and predicted values. The in vivo study, which was conducted on a fluorescein-loaded formulation that corresponded to the robust setpoint determined by QbD and that contained a mixture of polycaprolactone and Eudragit® FS (60:40, w/w), confirmed the colon-targeting qualities of this formulation.
Highlights
Inflammatory bowel disease (IBD) is a chronic, relapsing, and debilitating inflammatory disorder of the gastrointestinal tract (GIT), presenting two major forms: ulcerative colitis (UC) and Crohn’s disease (CD)
We focused on obtaining curcumin loaded microspheres with the following characteristics: high drug loading and entrapment efficiency, minimum drug release in the gastric simulated environment, and in the first hours spent in intestinal simulated environment and maximum drug release at the end of the 24 h dissolution study
The particle size and particle size distribution, drug loading, drug entrapment efficiency, and percentages of drug released in media simulating the GIT environment were identified as critical quality attributes (CQAs) of the final product, microspheres for colon-specific delivery
Summary
Inflammatory bowel disease (IBD) is a chronic, relapsing, and debilitating inflammatory disorder of the gastrointestinal tract (GIT), presenting two major forms: ulcerative colitis (UC) and Crohn’s disease (CD). The difference between UC and CD is the fact that in UC, the inflammation is limited to the colon, while CD affects any part of the GIT, commonly the terminal ileum or the perianal region [1]. Anti-inflammatory drugs (e.g., corticosteroids), aminosalicylates, immunosuppressants, antibiotics and targeted therapies (e.g., anti-TNF-α monoclonal antibodies) are mainly used in the treatment of IBD. The drawback of these drugs is the fact that they cause serious side effects such as osteoporosis, acute pancreatitis and infection, and diarrhea, the reason being their non-specific delivery at the site of inflammation and the long-term treatment period. The development of alternative agents with high therapeutic efficacy and low side effects on the one hand, and of a delivery system able to selectively target the inflamed colonic tissue on the other hand, are of critical importance [1,2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
