title: Application of thermal effusivity as a process analytical technology tool for monitoring and control of the roller compaction process.
abstract: The aim of this study was to examine the relationship between physical characteristics of compacted ribbons and their thermal effusivity in an attempt to evaluate the feasibility of using effusivity for in-process monitoring of roller compaction. In this study, thermal effusivity, solid fraction, tensile strength, and Young's modulus of ribbons of microcrystalline cellulose (MCC), anhydrous lactose, and placebo (PBO) formulations containing various ratios of MCC to anhydrous lactose (75:20, 55:40, 40:55, and 20:75) were determined at various compaction pressures (25-150 bars). The effusivity-square root of solid fraction relationship was linear for MCC and all the PBO formulations but was a second-order polynomial function for lactose. This could be due to the predominant deformation of lactose by brittle fracture, which might have significantly increased the number and size of contact points between particles, causing a change in thermal conductivity along with a density change. The effusivity-tensile strength and effusivity-Young's modulus relationships were best described by logarithmic functions for MCC but were linear for lactose up to a compaction pressure of 65 bars. There were similar relationships for effusivity with tensile strength and Young's modulus for all PBO formulations except PBO IV, which might have been due to the deformation of lactose, the largest component in this formulation. Strong correlations between effusivity and physical properties of ribbons were established. Although these correlations were formulation-dependent, they demonstrate the possibility of using effusivity as a tool in monitoring roller compaction.
authors.affiliation: Solids-Pharmaceutical R&D, Chemical and Pharmaceutical Development, Wyeth Research, Pearl River, NY 10965-1299, USA. ghorabm@wyeth.com
authors.forename: Mohamed K
authors.initials: MK
authors.lastname: Ghorab
authors.forename: Ramarao
authors.initials: R
authors.lastname: Chatlapalli
authors.forename: Shamim
authors.initials: S
authors.lastname: Hasan
authors.forename: Arwinder
authors.initials: A
authors.lastname: Nagi
mesh_terms: D000465:Algorithms; D002482:Cellulose / Q000737:chemistry*; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D008422:Materials Testing / Q000379:methods*; D011312:Pressure; D013678:Technology, Pharmaceutical / Q000379:methods*; D013817:Thermography / Q000379:methods*
chemical_list: D004337:Drug Carriers; D005079:Excipients; D002482:Cellulose; C109691:microcrystalline cellulose