title: Effect of particle shape of active pharmaceutical ingredients prepared by fluidized-bed jet-milling on cohesiveness.
abstract: Milling is a common procedure to improve bioavailability of many active pharmaceutical ingredients (APIs), which typically have low solubility in water. But such micronization can yield an increase in the cohesiveness of particles. Although particle cohesiveness is desirable for tablet strength in the subsequent formulation process, increased particle cohesiveness can lead to operational difficulties in a milling equipment due to compaction of particles inside. In this article, the impact of milling via a fluidized-bed jet-mill on the cohesive strength and interparticle force was studied using Ethenzamide as a pharmaceutical model compound. As a result, the particle shape was found to affect both the tensile strength of powder bed and the interparticle cohesive force. A powder bed, having relatively high void fraction by direct tensile test, shows a positive correlation between the cohesive force and the particle sphericity, while powders with low void fraction by diametral compression test show a positive correlation between the cohesive force and the angularity of the particle.
authors.affiliation: Banyu Pharmaceutical Co., Ltd., 9-1, Kamimutsuna 3-Chome, Okazaki, Aichi 444-0858, Japan. tadashi_fukunaka@merck.com
authors.forename: Tadashi
authors.initials: T
authors.lastname: Fukunaka
authors.forename: Kohta
authors.initials: K
authors.lastname: Sawaguchi
authors.forename: Boris
authors.initials: B
authors.lastname: Golman
authors.forename: Kunio
authors.initials: K
authors.lastname: Shinohara
mesh_terms: D000269:Adhesives; D000465:Algorithms; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D010316:Particle Size; D012457:Salicylamides / Q000737:chemistry; D013718:Tensile Strength; D014961:X-Ray Diffraction
chemical_list: D000269:Adhesives; D012457:Salicylamides; C018935:ethenzamide