(703c) Effect of Particle Properties and Formulation Composition on Sticking Behavior during Pharmaceutical Tabletting

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. While adequate flowability and tabletability are critical to attain during development for 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 investigates the effect of particle properties and formulation composition on sticking behavior during tabletting. Various active pharmaceutical ingredients (API) were blended with commercial grades of microcrystalline cellulose (MCC) ranging in size from 20-110 μm. Effects of particle size and surface area were systematically studied. Inter-particle adhesion was also studied by using a dry-coating technique to modify particle surface properties. This study concludes that both particle size/surface area and inter-particle adhesion force significantly affect sticking behavior. Tablets with higher tensile strength (i.e. higher inter-particle adhesion) comprised of API with lower surface area relative to the excipient surface area resulted in less sticking. This study also found that the difference between the tablet tensile strength of the blend, σ_Blend, and that of the API, σ_API, normalized by the surface area fraction of API in the blend, f_SA,API, correlates well with the rate of mass adhered to the punch. This quantity, referred to as the stinking index (SI), is shown below.

SI=(1/f_SA,API)*(σ_Blend - σ_API)

The sticking index can be used to assess effects of particle properties and formulation composition on sticking. In particular, the sticking index shows that the use of fine particle size/high surface area MCC (d₅₀ = 20 μm) in place of coarser grades of MCC significantly reduce sticking and may offer an effective and practical method of addressing sticking during formulation development.

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.