A QbD Approach for the Formulation and Control of Triclabendazole in Uncoated Tablets: From Polymorphs to Drug...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Analytical Chemistry

Background:

• Fascioliasis, a neglected tropical disease, is treated with triclabendazole (TCB).
• Optimizing TCB immediate-release tablet formulations requires understanding critical material attributes (CMAs) and critical process parameters (CPPs).
• Quality by Design (QbD) principles offer a systematic approach to pharmaceutical development and process control.

Purpose of the Study:

• To apply QbD principles for investigating the impact of TCB polymorphism and pharmacotechnical variables on immediate-release tablet development.
• To identify critical process parameters (CPPs) and critical material attributes (CMAs) affecting TCB tablet dissolution.
• To develop predictive models for TCB dissolution behavior and establish a green analytical method for CPP analysis.

Main Methods:

• Screening of CPPs and CMAs (polymorph type, excipients, compression force) using Plackett-Burman design.
• Development of a mathematical model linking CPPs to dissolution using multiple linear regression (MLR) and a central composite design.
• Establishment of a near-infrared spectroscopy coupled to partial least squares (NIR-PLSs) method for CPP analysis.

Main Results:

• Polymorphic purity and cornstarch were identified as critical process parameters (CPPs).
• The developed NIR-PLSs model accurately predicted CPPs in new samples (100 ± 3%).
• MLR dissolution predictions closely matched actual dissolution profiles (f2 = 85), validating the predictive model.

Conclusions:

• The integrated QbD approach provides a robust framework for TCB tablet formulation development and control.
• The study successfully linked TCB polymorphic composition and processing parameters to dissolution outcomes.
• The developed models serve as valuable tools for ensuring consistent pharmaceutical quality and targeted drug release.