Thermogravimetric detection of incompatibilities between atenolol and excipients using multivariate techniques

Marek Wesolowski,Barbara Rojek

doi:10.1007/s10973-013-3070-y

Abstract

The purpose of this research study was evaluation of the utility of two common multivariate techniques, agglomerative cluster analysis (CA) and principal component analysis (PCA), as supplementary means of detecting incompatibilities, which can occur between active pharmaceutical ingredients and excipients at the preformulation stage of a solid dosage form. For the detection of incompatibilities between atenolol (beta blocker) and selected excipients (mannitol, lactose, starch, methylcellulose, β-cyclodextrin, meglumine, chitosan, polyvinylpyrrolidone and magnesium stearate), the thermogravimetry (TG), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were chosen. The results have shown that compatibility between atenolol and an excipient can be identified in a CA dendrogram by two large clusters, from which one groups an excipient and physical mixtures with a high concentration of the excipient. Another cluster encompasses atenolol and mixtures with a high content of the drug. In the PCA plot, all samples are located along the first principal component axis (PC1), beginning from a single component located with the most negative PC1 value, through mixtures with gradually varying concentration of both ingredients, till the second component located close to the most positive PC1 values. The results have shown that CA and PCA fulfil their role as supporting techniques in the interpretation of the data acquired from the TG curves, and the obtained data are compatible with the results of DSC and FTIR analyses.

Highlights

In the preformulation study of solid dosage forms one major concern is whether the active pharmaceutical ingredient (API) will be compatible with any of the excipients, or in the case of combination drug products whether APIs are compatible with each other [1, 2]
The purpose of this research study was evaluation of the utility of two common multivariate techniques, agglomerative cluster analysis (CA) and principal component analysis (PCA), as supplementary means of detecting incompatibilities, which can occur between active pharmaceutical ingredients and excipients at the preformulation stage of a solid dosage form
The results have shown that CA and PCA fulfil their role as supporting techniques in the interpretation of the data acquired from the TG curves, and the obtained data are compatible with the results of differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) analyses

Summary

Introduction

In the preformulation study of solid dosage forms (tablets, capsules, granules or powders) one major concern is whether the active pharmaceutical ingredient (API) will be compatible with any of the excipients, or in the case of combination drug products whether APIs are compatible with each other [1, 2]. For the rapid and accurate evaluation of the possible compatibility of APIs with excipients and selecting excipients with suitable compatibility, a variety of techniques have been used, including thermal methods of analysis, i.e., differential scanning calorimetry (DSC), differential thermal analysis (DTA), and thermogravimetry (TG) as well as hot stage microscopy (HSM), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM) [3,4,5,6,7]. Evaluations and conclusions are made on the basis of the modifications observed in thermal curves of API in the absence and in the presence of excipient

Methods

Results

Conclusion