Abstract

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.

By Asma Irshad, Rabia Ismail Yousuf, Muhammad Harris Shoaib, Faaiza Qazi, Muhammad Talha Saleem, Fahad Siddiqui, Farrukh Rafiq Ahmed, Rauf-ur-Rehman, Sabahat Jabeen, Sadaf Farooqi, Momina Zarish Khan & Rida Masood