Measurement of Moisture Content in Pharmaceutical Tablets by Handheld Near-Infrared Spectrometer: Adopting Quality by Design Approach to Analytical Method Lifecycle Management

Abstract

Control of moisture content in pharmaceutical solids (raw materials and solid dosage forms) is a challenge to pharmaceutical development and manufacturing. Pharmaceutical solids come in several forms and presentations requiring different, and often lengthy, sample preparation methods for moisture determination. Rapid screening of samples for their moisture content calls for an analytical method that can provide in-situ measurement with no or minimal sample preparation. We presented a near-infrared (NIR) spectroscopic method for rapid and non-destructive measurement of moisture content in a pharmaceutical tablet product. A handheld NIR spectrometer was selected for the quantitative measurement because of its ease of use, low cost, and high signals selective to water absorption in the NIR spectral range. Analytical quality by design (QbD) principles were explored during method design, qualification, and continued performance verification to increase robustness and promote continuous improvement of the analytical procedure. The International Council for harmonization (ICH) Q2 validation criteria were followed for validation of its linearity, range, accuracy, repeatability, intermediate precision, and method robustness. Limit of detection and limit of quantitation were also estimated based on the multivariate nature of the method. Practical considerations were also given to method transfer and a lifecycle approach to implementation of the method.

Keywords: Analytical method lifecycle; Handheld spectrometer; Method validation; Moisture content; Near-infrared spectroscopy; Pharmaceutical analysis; Quality by design.