PANTOPRAZOLE SUSTAINED RELEASE TABLETS: QBD-BASED STATISTICAL DEVELOPMENT AND IN VITRO INVESTIGATIONS

Objective: The present study is an attempt to develop and evaluate the sustained release tablet formulations (oral) of pantoprazole sodium utilizing chitosan (CH) based in situ forming polyelectrolyte complex as retardant polymer. Methods: The traditional method of wet granulation was used to create various formulations employing a 1% w/w solution of CH in 1% acetic acid (cooled to about 4°C and neutralized) as a binder. The formulation was optimized using a two-factor, three-level face-centered Central Composite Design. The Design-Expert software (Stat-Ease 360 trial version, Minneapolis, MN) was employed for further analysis of obtained results. For the study of effect of critical material attributes (CMAs) (independent variables) on Critical Quality Attributes (response variables) multiple liner regression analysis was performed through generation of second-order polynomial models using software. The analysis of variance was utilized for validation of generated models. To establish the interaction and main effects of CMAs software generated contour plots and 3D response surface plots were used. The optimized formulations were assessed for a number of characteristics, including thickness, hardness, uniformity of weight, drug content, friability, and in vitro drug release. The pharmacokinetic parameters were examined using various mathematical models to investigate and elucidate the mechanism of drug release from the various formulations. Results: The drug release studies confirmed a zero-order sustained release of drug for 12 h. The polyelectrolyte complex formation (in situ) between anionic polymers and CH had been revealed by X-ray diffraction studies of polyelectrolyte complex gels. Conclusion: The polyelectrolyte complex formed between CH and anionic polymer (sodium starch glycolate) had not only provided a sustained drug release but also prevent the initial burst release of hydrophilic drugs.