Analytical Tools- Driven Compatibility and Processing Methods Study: A Case of Artemether-Lumefantrine Fixed Dose Combination Formulation

Abstract

Administration of Artemisinin based Combination Therapies (ACTs) especially artemether and lumefantrine fixed dose combination as a first line treatment in uncomplicated falciparum malarial illness received global acclamation and recommendation: This study was undertaken to devise the best way to incorporate artemether-lumefantrine (AL) as model drugs during processing without compromising quality. Utilization of analytical tools revealed how compatibility of formulation components and suitability of process methods were monitored and controlled to achieve quality outcome.  Excipients of proven performance in wet granulation method as well as AL as model drugs were designed into six formulations coded F-1 to F-6 to reflect modes of incorporation. Physical mixtures and wet granulated samples at different levels of processing were screened as in-process materials for compatibility and method suitability using Fourier Transform Infrared (FTIR), Differential Scanning Calorimetry (DSC) and High Performance Liquid Chromatography (HPLC) techniques. Assessment of potential risks inherent in formulation and process unit operations was adequately addressed by these instruments. Matching and comparison of spectra, thermograms and chromatograms at different levels of processing indicated that there were no disappearance of old or appearance of new spectral bands; showed reduction of melting endotherm and similar characteristic elution times of AL as they transformed from pure material to physical mixture (PM) and to granules. Results from this work alluded to compatibility of formulation components and suitability of processing techniques to the extent that the resultant granulates were good enough for further processing.