title: Monitoring process induced attrition of drug substance particles within formulated blends.
abstract: The aim of the study was to investigate the impact of unit processing steps such as blending, cone milling and powder feeding systems on the particle size of a formulated API. The particle properties of a single component (API) within formulated samples were tracked using an image based particle characterisation system with an integrated Raman probe. In addition to the primary aim, the impact of excipient selection was also assessed. The study demonstrated the ability to track the size and shape of particles of a single component within a blended system. Process induced attrition can affect significant changes in the size and shape characteristics of the API particles. Whilst blending and cone milling were found to have minimal impact on the API properties, significant particle attrition was induced through transmission of the formulations through a powder feeding system. The impact of excipients within the formulated blends on API attrition propensity was observed to be low. The findings suggest that the propensity for particles to undergo process induced attrition should be taken into consideration when designing a manufacturing process and/or relating initial particle properties to the performance of intermediate or final dosage forms.
authors.affiliation: Drug Product Science & Technology, Bristol-Myers Squibb, Reeds Lane, Moreton, Wirral CH46 1QW, UK. Electronic address: john.gamble@bms.com.
authors.forename: John F
authors.initials: JF
authors.lastname: Gamble
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK.
authors.forename: Magnus
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Drug Product Science & Technology, Bristol-Myers Squibb, Reeds Lane, Moreton, Wirral CH46 1QW, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Hughes
authors.affiliation: Drug Product Science & Technology, Bristol-Myers Squibb, Reeds Lane, Moreton, Wirral CH46 1QW, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Hutchins
authors.affiliation: Drug Product Science & Technology, Bristol-Myers Squibb, Reeds Lane, Moreton, Wirral CH46 1QW, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Tobyn
mesh_terms: D002482:Cellulose / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D013229:Stearic Acids; C031183:stearic acid; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose
keywords: Attrition; Imaging; Particle size; Pharmaceuticals; Raman spectroscopy