Defense Date

6-21-2005

Graduation Date

2005

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Pharmaceutics

School

School of Pharmacy

Committee Chair

James Drennen

Committee Member

Lawrence Block

Committee Member

Carl Anderson

Committee Member

Peter Wildfong

Committee Member

Mitchell Johnson

Keywords

Coating, Near-IR, NIR, Pelletization, Pharmaceutical, Process Control

Abstract

This study explored the potential of near-infrared spectroscopy in the determination of pharmaceutical pellet characteristics and to predict desired process endpoints during fluidized bed drug suspension layering and coating operations. Various strengths of diltiazem HCl pellets were prepared via a tangential-spray rotogranulation process and subsequently coated Eudragit RS30D in a Wurster column. In-line and at-line near-IR process monitoring methods were evaluated. Quantitative calibrations for potency, applied polymer solids and dissolution were developed using several different regression models. Both in-line and at-line determinations of pellet potency were effectively accomplished with average standard errors of prediction of 1.11% and 0.63%, respectively. Near-IR prediction of pellet potency of pilot-scale batches was also achieved using data from laboratory-scale experiments. For Wurster coating operations, in-line and at-line near-IR regression models for predicting applied polymer solids were developed which demonstrated R2 values of 0.98 or greater and standard errors of calibration less than 0.6%. Prediction of a t50% dissolution metric within 7 minutes of actual values was possible for pellets exhibiting 8 to 12 hour release characteristics. Qualitative assessment of applied polymer solids was also accomplished using Mahalanobis distance and bootstrap pattern recognition algorithms. This study has demonstrated the potential of near-IR spectroscopy in quantitative and qualitative assessment of pelletized pharmaceutical product characteristics and in the identification of process endpoints. Future implementation of these techniques could potentially reduce production cycle-times associated with the acquisition of laboratory test results and ensure product quality compliance throughout various stages pellet manufacturing.

Format

PDF

Language

English

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