Microcrystalline cellulose, lactose and lignin blends: Process mapping of dry granulation via roll compaction

In this study, a process map was developed in an effort to improve the understanding of dry granulation of pharmaceutical excipients by roll compaction process, and to implement the quality-by-design (QbD) approach. Through development of the process map, a correlation was made between the critical process parameters (roll pressure, screw speed), and critical quality attributes (density of ribbons and granule size). This method reduces development time, quantity of materials required and cost. A new excipient formulation based on natural polymers (lignin and cellulose) was utilised to improve the properties and reduce costs associated with tablets production. A variety of lignin, microcrystalline cellulose (MCC) and lactose monohydrate formulations were compacted followed by milling to obtain granules. Formulations were also characterised in terms of compressibility and flowability. Density of ribbons as well as granule size distribution were mapped versus critical process parameters. Based on this work as initial study, roll pressure was found to be a critical process parameter, higher ribbon density and larger granule size obtained with higher roll pressure. It was also revealed that the process map is a powerful tool in understanding the dry granulation, and can be used to construct a design space for pharmaceutical manufacturing.