Comprehensive powder flow characterization with reduced testing

Powder flow is a critical attribute of pharmaceutical blends to ensure tablet weight uniformity and production of tablets with consistent and reproducible properties. This study aims at characterizing different powder blends with a number of different rheologic techniques, in order to understand how particles’ attributes and interaction between components within the formulation generate different responses when analysed by different rheological tests. Furthermore, this study intends on reducing the number of tests in early development phases, by selecting the ones that provide the best information about the flowability attributes of the pharmaceutical blends. This work considered two cohesive powders – spray-dried hydroxypropyl cellulose (SD HPMC) and micronized indomethacin (IND) – formulated with other four commonly used excipients [(lactose monohydrated (LAC), microcrystalline cellulose (MCC), magnesium stearate (MgSt) and colloidal silica (CS)].

The experimental results showed that powder flowability may be affected by materials particles’ size, bulk density, morphology, and interactions with lubricant. In detail, parameters, such as angle of repose (AoR), compressibility percentage (CPS), and flow function coefficient (ff_c) have shown to be highly affected by the particle size of the materials present in the blends. On the other hand, the Specific Energy (SE) and the effective angle of internal friction (φe) showed to be more related with particle morphology and materials interaction with the lubricant. Since both ff_c and φe parameters are generated from the yield locus test, data suggest that a number of different powder flow features may be understood only by applying this test, avoiding redundant powder flow characterization, as well as extensive time and material spent in early development formulation stages.

Materials

Tablettose® 100 (LAC, alpha-lactose-monohydrate) was provided by MEGGLE–Pharma (Germany) and VIVAPUR® 101 (MCC, microcrystalline cellulose) was provided by JRS Pharma (Germany). Magnesium Stearate (MgSt) was acquired from Scharlab S.L., (Spain). CAB-O-SIL® M−5P fumed silica (CS, colloidal silica) was acquired from Cabot Corporation (USA). Hydroxypropyl methylcellulose E3 (SD HPMC) was purchased from Dupont (Germany) and Spray-Dried by Hovione Farmaciencia SA. (Portugal).

Catarina Chendo, João F. Pinto, Maria C. Paisana, Comprehensive powder flow characterization with reduced testing,
International Journal of Pharmaceutics, Volume 642, 2023, 123107, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.123107.