title: Effect of milling temperatures on surface area, surface energy and cohesion of pharmaceutical powders.
abstract: Particle bulk and surface properties are influenced by the powder processing routes. This study demonstrates the effect of milling temperatures on the particle surface properties, particularly surface energy and surface area, and ultimately on powder cohesion. An active pharmaceutical ingredient (API) of industrial relevance (brivanib alaninate, BA) was used to demonstrate the effect of two different, but most commonly used milling temperatures (cryogenic vs. ambient). The surface energy of powders milled at both cryogenic and room temperatures increased with increasing milling cycles. The increase in surface energy could be related to the generation of surface amorphous regions. Cohesion for both cryogenic and room temperature milled powders was measured and found to increase with increasing milling cycles. For cryogenic milling, BA had a surface area ∼ 5× higher than the one obtained at room temperature. This was due to the brittle nature of this compound at cryogenic temperature. By decoupling average contributions of surface area and surface energy on cohesion by salinization post-milling, the average contribution of surface energy on cohesion for powders milled at room temperature was 83% and 55% at cryogenic temperature.
authors: Surfaces and Particle Engineering Laboratory (SPEL), Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors: Umang V
authors: UV
authors: Shah
authors: Surfaces and Particle Engineering Laboratory (SPEL), Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors: Zihua
authors: Z
authors: Wang
authors: Bristol-Myers Squibb Co., One Squibb Drive, New Brunswick, NJ 08902, USA.
authors: Dolapo
authors: D
authors: Olusanmi
authors: Bristol-Myers Squibb Co., One Squibb Drive, New Brunswick, NJ 08902, USA.
authors: Ajit S
authors: AS
authors: Narang
authors: Bristol-Myers Squibb Co., One Squibb Drive, New Brunswick, NJ 08902, USA.
authors: Munir A
authors: MA
authors: Hussain
authors: Bristol-Myers Squibb Pharmaceuticals, Reeds Lane, Moreton, Wirral CH46 1QW, UK.
authors: Michael J
authors: MJ
authors: Tobyn
authors: Surfaces and Particle Engineering Laboratory (SPEL), Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Electronic address: jerry.heng@imperial.ac.uk.
authors: Jerry Y Y
authors: JYY
authors: Heng
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D010316:Particle Size; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D014227:Triazines / Q000737:chemistry*
chemical_list: D014227:Triazines; C509922:brivanib; D000409:Alanine
keywords: Cohesion; Milling temperature; Milling time; Silanisation; Surface area; Surface energy