(301d) The Use of Fine Excipients to Improve the Manufacturability of Pharmaceutical Tablets

Tablets comprise the majority of pharmaceutical products for oral solid dosage forms in part due to their low cost of manufacturing, convenience of dosing to patients, and high stability. Tablets are typically produced by compacting powders or granules in a die using a rotary press. The formulation intended for tabletting must have adequate flow properties to consistently fill a tabletting die from a hopper and must also have sufficient compression properties to form a tablet with the mechanical strength to undergo subsequent coating, packaging, and handling. Because the drug substance is often poorly flowing and poorly compactable, it is necessary to add fillers, glidants, lubricants, or other excipients to obtain a manufacturable formulation.

The recent work of Capece et al. [1] showed that the tabletability of formulations can be significantly improved by using fine sized excipients (20 μm) while also maintaining adequate flowability. This novel approach is contrasted by the common and conventional formulation strategy of using coarse sized excipients which usually have a mean size of about 100 μm. Due to the greater number of high strength bonds provided by contacts between fine excipients, tablet tensile strength is increased even at high drug loadings (>50%). In addition, the use of fine excipients can also enable the use a direct compaction process.

While adequate flowability and tabletability are critical to attain during development for all formulations intended for tableting, some drug substances may also have a propensity to adhere to the tableting punch. So-called sticking can result in cosmetic defects or can prevent manufacturing altogether for an otherwise acceptable formulation. This work further investigates the use of fine excipients to improve the manufacturability of tablets with a focus on sticking. The effect of various sizes of a common excipient, microcrystalline cellulose, on the sticking propensity of a proprietary pharmaceutical active is investigated. To quantify sticking propensity, a removable-tip punch is used to quantify the mass of material adhered to the punch surface. The work shows that fine sized excipients can reduce and prevent sticking while also improving tabletability. This is due to the reduction of surface area of the sticky drug substance relative to the non-sticky excipient as well as the increase in the number of high strength bonds in the formulation. The reduction in sticking and the increase in tabletability give further credence to a formulation strategy that uses fine sized excipients in place of more commonly used coarse sized excipients.

[1] M. Capece, Z. Huang, R. Davé. Insight into a novel strategy for the design of tablet formulations intended for direct compression. J. Pharm. Sci. 106 (2017) 1608-1617.

All authors are employees of AbbVie. The design, study conduct, and financial support for this research was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.