Development of a Curcumin-Loaded Polymeric Microparticulate Oral Drug Delivery System for Colon Targeting by Quality-by-Design Approach
Dana Hales,
Lucia Ruxandra Tefas,
Ioan Tomuță,
Cristian Moldovan,
Diana Gulei,
Raluca Munteanu,
Alina Porfire
Affiliations
Dana Hales
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Haţieganu”, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
Lucia Ruxandra Tefas
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Haţieganu”, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
Ioan Tomuță
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Haţieganu”, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
Cristian Moldovan
Research Center for Advanced Medicine—MedFUTURE, University of Medicine and Pharmacy “Iuliu Haţieganu”, 4-6 L. Pasteur Street, 400349 Cluj-Napoca, Romania
Diana Gulei
Research Center for Advanced Medicine—MedFUTURE, University of Medicine and Pharmacy “Iuliu Haţieganu”, 4-6 L. Pasteur Street, 400349 Cluj-Napoca, Romania
Raluca Munteanu
Research Center for Advanced Medicine—MedFUTURE, University of Medicine and Pharmacy “Iuliu Haţieganu”, 4-6 L. Pasteur Street, 400349 Cluj-Napoca, Romania
Alina Porfire
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Haţieganu”, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
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.
