title: On the relationship of inter-particle cohesiveness and bulk powder behavior: Flowability of pharmaceutical powders.
abstract: This study investigates the relationship between particle interactions dominated by the cohesive van der Waals force and powder flowability for materials commonly used by the pharmaceutical industry in oral solid dosage formulation. This study first sought to correlate the granular Bond number, defined as the ratio of the inter-particle cohesion force to particle weight, to the flow function coefficient, a metric commonly used to assess powder flowability. However, the granular Bond number which strictly quantifies inter-particle cohesiveness was found to correlate poorly with powder flowability due to the complexity associated with particle assemblies. To account for the multitude of interactions between particles of different sizes within a powder and to more precisely predict bulk powder behavior, a population-dependent granular Bond number was proposed. The population-dependent granular Bond number which explicitly accounts for particle size distribution and described herein as a quantification of powder cohesiveness (instead of inter-particle cohesiveness) was shown to correlate well with the flow function coefficient for a wide variety of materials including four active pharmaceutical ingredients (APIs) and fourteen common pharmaceutical excipients. Due to the success of the population-dependent granular Bond number, it was extended to predict the flowability of powder blends. This so-called population-dependent multi-component granular Bond number takes into account relevant material properties and particle interactions and was used to predict the flowability of 6-component powder blends containing acetaminophen as a model cohesive active pharmaceutical ingredient. Prediction of bulk powder behavior from individual material properties as accomplished here may be highly useful in formulation development.
authors.affiliation: Drug Product Development, Research and Development, AbbVie Inc., North Chicago, IL 60064, United States. Electronic address: maxx.capece@abbvie.com.
authors.forename: Maxx
authors.initials: M
authors.lastname: Capece
authors.affiliation: Lorena School of Engineering, University of São Paulo, Lorena, São Paulo 12.602-810, Brazil.
authors.forename: Karina Ruiz
authors.initials: KR
authors.lastname: Silva
authors.affiliation: Drug Product Development, Research and Development, AbbVie Inc., North Chicago, IL 60064, United States.
authors.forename: Divya
authors.initials: D
authors.lastname: Sunkara
authors.affiliation: Drug Product Development, Research and Development, AbbVie Inc., North Chicago, IL 60064, United States.
authors.forename: John
authors.initials: J
authors.lastname: Strong
authors.affiliation: Drug Product Development, Research and Development, AbbVie Inc., North Chicago, IL 60064, United States.
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011208:Powders; D012212:Rheology / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D011208:Powders
keywords: Flow function coefficient; Formulation development; Granular bond number; Inter-particle cohesion; Powder flowability