Effect of starch, cellulose and povidone based superdisintegrants in a QbD-based approach for the development and optimization of Nitazoxanide orodispersible tablets: Physicochemical characterization, compaction behavior and in-silico PBPK modeling of its active metabolite Tizoxanide

The objective of the study was to develop a QbD based orodispersible Nitazoxanide 200 mg tablets its in-silico PBPK modeling. The central composite design was applied to study the effect of four different superdisintegrant i.e., starch and cellulose based (sodium starch glycolate, pre-gelatinized starch, croscarmellose sodium), and crospovidone with microcrystalline cellulose as independent variables on disintegration time and % drug release. The Heckel analysis was applied to determine the compression behavior of the formulations which revealed a yield pressure in the range of ∼119 MPa–∼138 MPa. Moreover, the hardness of the tablets increased with the compression force and was largely independent of the disintegration time (<3 min for a maximum pressure of ∼138 MPa) owing to the role of superdisintrgrants in the formulations. The quality attributes suggest that the formulations containing microcrystalline cellulose (11–15%) with sodium starch glycolate (8%), pregelatinized starch (7.185%), croscarmellose sodium (2.755%), and crospovidone (5%) at the maximum desirability (0.799–0.902) exhibited minimum disintegration time and maximum % drug release. Their dissolution data (pH 1.2) were applied to predict the pediatric plasma profile of the active metabolite Tizoxanide by PBPK modeling. The QbD-based approach was successfully applied in designing Nitazoxanide 200 mg orodispersible tablets.