466116 Development of a Model Predictive Tool for Continuous Manufacturing of Solid Oral Dosage Forms Via Roller Compaction
Monday, November 14, 2016
Grand Ballroom B (Hilton San Francisco Union Square)
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Continuous Manufacturing (CM) is currently receiving significant attention in the pharmaceutical industry. In the past, common manufacturing processes for oral solid dosage (OSD) forms relied on batch processing followed by final product testing to ensure the desired quality has been achieved. This approach is considered inefficient due to increased material consumption and prolonged processing times. Therefore, it is crucial to take a step towards model predictive CM to enable prediction of the final tablet critical quality attributes (CQAs). To develop a quality by design (QbD) framework, a compaction and compression integrated work stream has been developed to enable prediction of compaction and compression behaviour of various powders and their blends. The blends consist of varying amounts of active pharmaceutical ingredient (API), 1 wt% lubricant and as remainder microcrystalline cellulose (MCC). These are either directly compressed or compressed after dry granulation via roller compaction. This work develops a real time control tool to predict final tablet CQAs based on powders with varying properties. This tool will ultimately provide control of roller compaction and tablet press settings to produce desired tablet properties. For the development of this tool a detailed understanding of the impact of powder properties on the compression and compaction behaviour was established. Three different model APIs were used in this study to establish the production limits and to define the optimised process settings of the roller compactor and tablet press. Each API displays a different morphological structure (spherical, monocline and needle shaped) that produces varying flow, compaction and compression characteristics. Experimental work was carried out using various (10 – 40 wt%) API loadings to establish the optimal compaction and compression conditions. The resulting experimental data was analysed to identify the key process parameters, which were linked to the model predictive tool. A top fed roller compactor was used under ambient conditions with varying screw speed (12 – 24 rpm), roller speed (3 - 5 rpm) and roller pressure (10 - 20 bar) for ribbon production. The ribbon density, which is a key factor of roller compaction, was analysed with a GeoPyc 1360 envelope density analyser. The ribbons were granulated in a conical mill (Comil) and analysed for particle size distribution using sieving and a Microtrac Particle Size Analyser. The granule produced was compacted into tablets using various die sizes (6, 8, 10 and 12 mm) and a single punch Manesty F3 tablet press. Displacement measurements were assessed using commercial and custom built compaction testing equipment to determine compaction behaviour of powders and their blends. The tablets were tested for properties, including weight consistency, hardness, thickness, diameter, friability, dissolution and disintegration time.