Abstract The purpose of this study is to optimize the composition of extragranular excipients (EGE) and mixing time of granules with EGE of paracetamol tablet formulation using Design of Experiments (DoE) approach. The effect of the composition of EGE and the mixing time of granules with EGE on granule and tableting properties of paracetamol tablet formulation was investigated using a combined model of mixture and process factors (Design-Expert 12). A total of 18 tablet formulations were manufactured by wet granulation using varying compositions of EGE and varying mixing time. Granule and tablet properties of each formulation were evaluated as response variables for the design, data generated were fitted into models and analysed to generate a design space that was used for optimization studies. The proposed EGE composition as predicted by the design was confirmed and validated after preparation and evaluation of the granule and tablet properties. The optimized composition for the EGE that yielded granules and tablets of desirable characteristics was found to be maize starch (5 %), talc (4.9 %) and magnesium stearate (0.1 %) with a mixing time of 2 min. The tablets produced with the optimized composition had better mechanical strength and disintegration time than the formulation prepared using an existing formula of maize starch (7.8 %), talc (2 %) and magnesium stearate (0.2 %) that were obtained using the One Variable at a Time (OVAT) approach. This study confirmed the relevance of quality by design in development of pharmaceutical formulations.

ABSTRACT Objective: The aim of this study was to evaluate the performance of maize starch as a multifunctional excipient in metronidazole tablet formulation. Methods: Metronidazole tablets were prepared by wet granulation containing maize starch as diluent (40 %), disintegrant (10 %), and binder (5 %) and compared with a reference formulation containing lactose as diluent (40 %), maize starch as disintegrant (10 %) and acacia as binder (5 %). The granules were analysed for particle size, flow properties, compressibility and moisture content. Tablets weighing 500 mg were compressed for both formulations on a Single Punch Tablet Press using a 12 mm flat-faced punches at 57.5 MPa. The tablets were kept for 24 h to allow for elastic recovery and evaluated for weight and content uniformity, thickness, crushing strength, friability, disintegration time and in vitro drug release. Results: The granule properties revealed differences in mean granule size, angle of repose, bulk and tapped densities for both formulations. Batch I tablets gave rise to better tableting properties compared to batch II tablets. Conclusion: This study confirms the suitability of maize starch as a multifunctional excipient in tablet formulation.

RESUMEN Objetivo: El objetivo de este estudio fue evaluar el rendimiento del almidón de maíz como excipiente multifuncional en la formulación de comprimidos de metronidazol. Métodos: Metronidazol Tabletas En Honorario preparado por granulación húmeda que contiene almidón de maíz como diluyente (40%), desintegrante (10%) y aglutinante (5%) y en comparación con una formulación de referencia que contiene lactosa como diluyente (40%), almidón de maíz como desintegrante (10%) y Acacia como aglutinante (5%). Los gránulos se analizaron para el tamaño de partícula, propiedades de flujo, compresibilidad y contenido de humedad. Las tabletas con un peso de 500 mg fueron comprimidas para ambas formulaciones en una simple Punch Tablet Press usando un punzón de 12 mm de cara plana en 57,5 MPa. Los comprimidos se mantuvieron durante 24 h para permitir la recuperación elástica y evaluar el peso y el contenido uniformidad, espesor, resistencia a la trituración, friabilidad, tiempo de desintegración y in vitro liberación de drogas. Resultados: Las propiedades del gránulo revelaron diferencias en el tamaño medio del gránulo, el ángulo de reposo, las densidades a granel y roscado para ambas formulaciones. Los comprimidos de Batch I dieron lugar a mejores propiedades de comprimidos en comparación con los comprimidos de lote II. Conclusión: Este estudio confirma la idoneidad del almidón de maíz como excipiente multifuncional en la formulación de comprimidos.