Multivariate calibration of energy-dispersive X-ray diffraction data for predicting the composition of pharmaceutical tablets in packaging

Robert D Speller,Chiaki Crews,Daniel O’Flynn,Peter S Kenny

doi:10.1016/j.jpba.2017.12.036

Abstract

A system using energy-dispersive X-ray diffraction (EDXRD) has been developed and tested using multivariate calibration for the quantitative analysis of tablet-form mixtures of common pharmaceutical ingredients. A principal advantage of EDXRD over the more traditional and common angular dispersive X-ray diffraction technique (ADXRD) is the potential of EDXRD to analyse tablets within their packaging, due to the higher energy X-rays used.In the experiment, a series of caffeine, paracetamol and microcrystalline cellulose mixtures were prepared and pressed into tablets. EDXRD profiles were recorded on each sample and a principal component analysis (PCA) was carried out in both unpackaged and packaged scenarios. In both cases the first two principal components explained >98% of the between-sample variance. The PCA projected the sample profiles into two dimensional principal component space in close accordance to their ternary mixture design, demonstrating the discriminating potential of the EDXRD system.A partial least squares regression (PLSR) model was built with the samples and was validated using leave-one-out cross-validation. Low prediction errors of between 2% and 4% for both unpackaged and packaged tablets were obtained for all three chemical compounds. The prediction capability through packaging demonstrates a truly non-destructive method for quantifying tablet composition and demonstrates good potential for EDXRD to be applied in the field of counterfeit medicine screening and pharmaceutical quality control.

Highlights

energy-dispersive XRD (EDXRD) is a powerful tool for characterizing the chemical composition of crystalline materials
Materials which fall into this category include powder-form illicit drugs and plastic explosives, both of which have been studied using EDXRD [1,2,3]
A recent study has demonstrated that chemically-relevant features from EDXRD data can be observed for aspirin tablets when they are within blister packaging [4]

Summary

Introduction

EDXRD is a powerful tool for characterizing the chemical composition of crystalline materials. Materials which fall into this category include powder-form illicit drugs and plastic explosives, both of which have been studied using EDXRD [1,2,3]. The advantages of this technique include the use of high-energy photons which are capable of penetrating the surface of materials and characterising the layers beneath. This is a highly attractive capability in security screening contexts and for the determination of medicine quality. A quantitative analysis of unpackaged pharmaceutical formulations using EDXRD and mul-

Methods

Results

Conclusion