Dramatic reduction of resources needed to transfer NIR blend analysis methods from laboratory to full-scale equipment (original) (raw)

2014

Abstract

ABSTRACT Here, we describe an approach for creation of matched near-infrared absorption spectra of pharmaceutical powders in a blender by using a small amount of pharmaceutical blends in a die and well-controlled application of force. Recently, pharmaceutical development has followed quality by design (QbD) concepts. Pharmaceutical companies are increasingly using near-infrared spectroscopy (NIRS) as a quality monitoring tool for their products from development stages to commercial productions. Such applications are integral for process control strategies and real time release testing (RTRt). NIRS is a mature process analytical technology (PAT) tool. It has been widely applied for blend-endpoint monitoring. However, the resources required to conduct development experiments at pilot and commercial scale are often prohibitive because of limited supply and costs of active pharmaceutical ingredients (APIs). Such trials are frequently critical because the differences of the process scale have a large impact on NIR spectra. These differences in NIR spectra prevent the simple transfer of a model for predicting concentration from small scale development equipment to pilot or commercial scale. Transfer from the lab scale to larger scale is based on simulating the effect of scale in the laboratory environment using small amounts of material. Careful application of force to pharmaceutical blends in a small die matched conditions of pharmaceutical blends at different scales. A small amount of material in a 5cm die was only used for these blend simulation studies. The impact of this work is that fully transferable methods are developed using small quantities of pharmaceutical blends ( << 1 kg). Principal component analysis (PCA), two-dimensional (2D) correlation spectroscopy analysis and Hotteling’s T2 ellipse results demonstrated that NIR spectra obtained in the experimental apparatus matched NIR spectra in a blender. This approach has the potential to dramatically reduce the material costs used for NIRS research of blending process.

James Drennen hasn't uploaded this paper.

Let James know you want this paper to be uploaded.

Ask for this paper to be uploaded.