(T1530-11-64) A Rational Approach to Scaling-Up Lubrication in Pharmaceutical Tablet Manufacturing

Purpose: Lubricants play a crucial role in manufacturing of oral solid dosage forms, ensuring smooth operation and consistent quality of the final product. Scaling up the lubrication process can pose significant challenges. It impacts the blend and tablet characteristics, such as hardness, disintegration time, and dissolution. This study aims to develop a rational approach, based on Kushner’s lubrication length scale [1] and the Froude number, to maintain consistent blend properties during scale-up and ensure uniform tablet properties.

Methods: This study was designed to identify methods that lead to the efficient scale up of a lubrication process resulting in consistent tablet quality. The amount of shear and the number of revolutions (NOR) are key process parameters that impact tabletability. To understand these effects, two scale-up methodologies were compared: (1) a conventional constant NOR; and (2) a new methodology combining constant Froude number and the lubrication length. This study used powder mixtures of MCC and Lactose with Magnesium Stearate (Mg St) as the lubricant (69.3% w/w MCC PH 102, 29.7% w/w lactose 60M and 1% w/w Mg St). Blending was conducted in 1L and 8L vessels using an Erweka AR 403 BB15 mixer. De-lumping was achieved by hand screening using a 1 mm mesh sieve. Powders were compacted using a compaction simulator (Styl’One™ Evolution) with constant weight filling (300 mg) and 11.28 mm Euro-B FF tooling. Scaling was evaluated from 1L to 8L vessels. Figure 1 shows the blending experiments performed.

Results: Figure 2 summarizes the tablet properties across different scales. The results demonstrate that the methodology combining constant Froude number and the lubrication length provide consistent tabletability while maintaining target hardness with the same compression force. Conversely, the constant NOR approach resulted in decreased hardness showing inconsistent lubrication and tabletability. These results highlighted that the proposed methodology provides a reliable and scalable lubrication approach compared to the NOR method.

Conclusion: The approach of combining constant Froude number and the lubrication length provided a reliable approach to scale-up lubrication process. It demonstrated uniform blend properties across different manufacturing scales and ensured consistent product quality.

References: [1] Joseph Kushner, Francis Moore, Scale-up model describing the impact of lubrication on tablet tensile strength, International Journal of Pharmaceutics, Volume 399, Issues 1–2, 2010, Pages 19-30, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2010.07.033.