title: Effect of tapped density, compacted density, and drug concentration on light-induced fluorescence response as a process analytical tool.
abstract: The effect of tapped density, compacted density, and fluorescent drug concentration on the light-induced fluorescence (LIF) response is reported. The fluorescent response to powder mixtures containing 0.25%-10.00% w/w fluorescent active pharmaceutical ingredient (API) was evaluated over a density range of about 0.641-1.370 g/cm(3) . Blend concentrations up to 4.00% w/w API showed a linear trend in LIF response with increasing tapped and compacted density. API concentrations of 4.00% w/w or greater exhibited a negative parabolic trend in LIF response. The LIF responses were fitted to a quadratic model equation that included an interaction term between material density and API concentration (adjusted R(2) = 0.975 and p < 0.0001). All model terms were highly significant, including the material density-API concentration interaction (p < 0.0001). Being aware of the sensitivity of the LIF response to material density changes and the related changes in apparent concentration are important in implementing LIF as a process analytical tool for processes such as blending, roller compaction, and tableting.
authors.affiliation: Campbell University College of Pharmacy and Health Sciences, Department of Pharmaceutical Sciences, Buies Creek, North Carolina; PRA Health Sciences, Data and Clinical Programming Department, Horsham, Pennsylvania.
authors.forename: Ishan G
authors.initials: IG
authors.lastname: Shah
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Ely
authors.forename: William C
authors.initials: WC
authors.lastname: Stagner
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005453:Fluorescence; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations
keywords: compacted density; compaction; content uniformity; fluorescence spectroscopy; light-induced fluorescence (LIF); mathematical model; process analytical technology (PAT); processing; tapped density