Quality by Design Approach for Optimization of Microbial and pH-Triggered Colon-Targeted Tablet Formulation Using...

ABSTRACT The purpose of this study was to apply the quality by design (QbD) approach in the development of a microbial and pH-triggered colon-targeted budesonide tablet. A retrospective research strategy was used to select various polysaccharide-based natural gums such as tamarind gum, gellan gum, karaya gum, gum ghutti, and khaya gum, which were then evaluated for their effectiveness in microbial degradation and targeting the colon. Viscosity profiles were generated in the presence of a prebiotic culture medium prepared by using the Velgut capsule that mimicked the impact of 4% rat cecal content and helpful in screening of natural polymer. Based on the cumulative drug release data of preliminary batches, carboxymethyl (CM) tamarind gum was identified as a superior and an excellent polymer over the tamarind gum for formulation development. The presence of water as a bridging agent in wet granulation also played an important role in the retardation of drug release. Tablets were supercoated with the enteric polymer, Eudragit S100. The Box-Behnken design was utilized, where the selected independent variables were the proportion of CM tamarind gum, % water proportion, and % weight gain of Eudragit S 100 to optimize the formulation. The optimized design space was generated with the criteria that a drug release should be of less than 5% within the first 2 h, less than 10% within the first 5 h, and more than 70% within the first 8 h, to achieve colon targeting. The optimized batch F3 was found stable as per International Council for Harmonisation guidelines. The roentgenography study for optimized formulation demonstrated that it remained intact for 5 h and, at 7 h, was disseminated completely. CM tamarind gum is efficient for colon targeting, and its proportion in 100 mg along with an enteric coating of 6% led to the optimized formulation.