QUALITY BY DESIGN-BASED FORMULATION AND OPTIMIZATION OF ARTEMETHER - LUMEFANTRINE FIXED DOSE COMBINATION: TABLETS EVALUATION
Abstract
Platform of quality by design (QbD) was explored to demonstrate within design space (DS) how inherent variations in materials and process were monitored and controlled to achieve robust process and quality product. This study was undertaken to evaluate tablets of Artemether - Lumefantrine (AL) fixed dose combination with a view to establish the fitness for purpose designed and built into the tablets. Tablets were compressed at predetermined compression force (40 MN/m2) and qualities were profiled in line with predefined Quality Target Product Profile (QTPP) and DS. Analytical tools such as Fourier Transform Infra-Red (FTIR) and Differential scanning calorimetry (DSC) were engaged to elucidate what transpired during tablet processing; evaluation of potential risks to predefined QTPP and critical quality attributes (CQAs) was done and documented. Optimization process was concluded within DS and observed quality features demonstrated the criticality of process unit operations. Evidence from screening showed that inherent potential risks to tablets were properly curtailed to the extent that fairly good tablets from F-4 and F-6 were alluded to. FTIR spectral bands showed no disappearance of important old peaks and no appearance of new ones as DSC thermograms indicated no thermal disequilibrium but better pharmaceutical parameters arising from reduction in melting endotherm. It is opined that tableting as a process was robust and capable of delivering good performance on a reproducible basis given the observed quality attributes of the 2 formulations.
Keywords: Design space, quality, robustness, performance, processing, optimization
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