(W1030-08-52) Optimization of Roller Compaction Process Parameters and Roller Design of Poorly Flowing Powder Blend

Purpose: To optimize roller compaction parameters and roller design of poorly flowing blend.

Methods: The formulation and manufacturing process were developed at small-scale, containing about 50% of a poorly flowing excipient. The manufacturing process consisted of dry granulation followed by encapsulation and check weighing. The granulation using Gerteis Minipactor® with knurled rollers resulted in challenges producing ribbons and granules at consistent parameters due to poor blend flow. To address this technical challenge, an additional study was designed with four selected process parameters (roller design, roller gap, roller force and roller speed). The impact of these process parameters was evaluated on the ribbon and milled granule properties. A total of seven (7) sublots including a center point were granulated as summarized in Attachment 1. Roller gap and roller forces were studied at 2 levels (low and high), roller speed was studied at 1 level (high), and roller design was studied at 2 levels (knurled rollers and axial grooved rollers). The tamp auger torque and gap range during roller compaction, ribbon envelope density, granule particle size distribution, and bulk/tapped density were measured for each sublot.

Results: The data collected from these experiments using Gerteis Minipactor® with axial grooved rollers was compared with the historical data collected from Gerteis Minipactor® with knurled rollers. Results from the Gerteis Minipactor® displayed the impact of roller design on the ability for the roller compactor to form granules during manufacturing. Both gap width (Attachment 2) and tamp auger torque (Attachment 3) showed relatively lower variance with axial grooved rollers compared to knurled rollers. Gap width variance decreased from 0.5 – 6.0 mm to 0.5 – 2.2 mm and tamp auger torque decreased from 0 – 18 Nm to 0.5 – 9 Nm with axial grooved rollers. Results from ribbon density tests showed that while density fluctuated slightly as process parameters were altered (~0.5 g/cm3), no observable trend was seen across trials. The same effect was observed in the particle size distribution (PSD) data. The proportion of milled granules retained on the # 200 mesh varied by ~4 %, however there was no observable trend towards any of the tested parameters. While there were clear improvements in ribbon/granule formation during the granulation process using axial grooved rollers, this effect was not shown to impact ribbon density or PSD data.

Conclusion: The study results indicated that the usage of axial grooved rollers for dry granulation of the pre-blend on Gerteis Minipactor® positively impacted the granulation process by minimizing variation in parameters such as gap width and tamp auger torque. The studied ranges of roller compaction parameters using axial grooved rollers showed minimal to no impact on physical properties of the blend. Therefore, the studied ranges of roller compaction parameters are recommended for future manufacturing batches.

Attachment 1: Study Design for Process Parameters

Attachment 2: Gap Width Results Using Knurled and Axial Grooved Rollers on Gerteis Minipactor

Attachment 3: Tamp Auger Torque Results Using Knurled and Axial Grooved Rollers on Gerteis Minipactor