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DOI: 10.1208/s12249-011-9667-1Pages: 1031-1037

Monitoring Powder Blend Homogeneity Using Light-Induced Fluorescence

1. Campbell University, College of Pharmacy & Health Sciences, Department of Pharmaceutical Sciences

2. Nova Southeastern University School of Pharmacy

3. Biodelivery Sciences International

4. GlaxoSmithKline

Correspondence to:
William C. Stagner
Tel: +1-910-8931836
Fax: +1-910-8931697
Email: stagnerw@campbell.edu

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Abstract

Light-induced fluorescence (LIF) was evaluated as a process analytical technology to monitor blend homogeneity and establish a relationship with high-performance liquid chromatography (HPLC). Secondary aims for this study included a determination of blend steady-state, acceptable mixing time interval, and mixing end point. Also, identification of potential “dead spots” in the 124 L intermediate bulk container mixing tote was explored. Individual samples from 13 sample locations were collected at 0.25, 0.5, 0.75, 1, 2, 5, 10, and 20 min and analyzed using LIF and HPLC. LIF and HPLC methods showed similar mixing profiles. A coefficient of determination (R2) of 0.86 (p value < 0.0001) was obtained for a second-degree polynomial bivariate fit of LIF counts by HPLC percent label claim (%LC). A significant linear relationship was determined between LIF percent relative standard (%RSD) and HPLC %RSD (R2 = 0.97, p < 0.0001). The LIF steady-state, acceptable mixing time interval, and mixing end point were determined to be 1–20, 2–20, and 2 min, respectively. The steady-state, acceptable mixing time interval, and mixing end point determined by HPLC were 1–20, 5–10, and 5 min, respectively. The Tukey–Kramer honestly significant difference analysis of HPLC %LC by sample location at 5 and 10 min mixing times showed that there was a statistical difference between the HPLC %LC group means at two blender locations.

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  • Accepted: Jul 16, 2011
  • Online: Aug 13, 2011

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