Pharmaceutical applications of vibrational chemical imaging and chemometrics: a review.

The emergence of chemical imaging (CI) has gifted spectroscopy an additional dimension. Chemical imaging systems complement chemical identification by acquiring spatially located spectra that enable visualization of chemical compound distributions. Such techniques are highly relevant to pharmaceutics in that the distribution of excipients and active pharmaceutical ingredient informs not only a product's behavior during manufacture but also its physical attributes (dissolution properties, stability, etc.). The rapid image acquisition made possible by the emergence of focal plane array detectors, combined with publication of the Food and Drug Administration guidelines for process analytical technology in 2001, has heightened interest in the pharmaceutical applications of CI, notably as a tool for enhancing drug quality and understanding process. Papers on the pharmaceutical applications of CI have been appearing in steadily increasing numbers since 2000. The aim of the present paper is to give an overview of infrared, near-infrared and Raman imaging in pharmaceutics. Sections 2 and 3 deal with the theory, device set-ups, mode of acquisition and processing techniques used to extract information of interest. Section 4 addresses the pharmaceutical applications.

Monitoring galenical process development by near infrared chemical imaging: one case study.

The objective of this study is to evaluate by NIR imaging the homogeneity of process intermediates obtained with different process parameters during the development of a new pharmaceutical solid form. The process under investigation is a solid dosage form based on extrusion. The parameters are two kinds of crystallizations, two sizes of particle of API, two screw speeds during the extrusion and two milling screens used to reduce the extrudates into a granulate form. Two kinds of intermediates are evaluated: the extrudates and the cores. Two approaches are used to analyze the data: the univariate NIR analysis which consists in wavelength selection and multivariate analysis, i.e., Classical Least Squares (CLS), which takes into account the whole spectra. The univariate method reveals good chemical homogeneity of the extrudates but differences in their physical aspect. CLS shows well-distributed excipients for all the cores; differences in the sizes of the granules have also been revealed. The univariate method can be applied on simple chemical systems such as binary mixtures. When complex samples are analyzed, multivariate analysis is the method of choice. This study demonstrates that NIR imaging can be a useful tool for the optimization of the process and for the selection of the final parameters of the process.

Characterizing process effects on pharmaceutical solid forms using near-infrared spectroscopy and infrared imaging.

Near-infrared spectroscopy (NIRS) has become a widely used analytical technique in the pharmaceutical industry, serving for example to determine the active substance or water content of tablets. Its great advantage lies in the minimal sample preparation required and speed of measurement. In a study designed to detect the effects of process on tablet dissolution, we describe the application of NIRS to the detection and identification of changes in uncoated and coated tablets in response to pilot-scale changes in process parameters during melt granulation, compression, and coating. Beginning with a qualitative comparison between pharmaceutical batches, we show that NIRS and principal component analysis can separate batches produced with different melt granulation parameters and differentiate between cores compressed with different compaction forces. Complementary infrared imaging can also explain the difference in dissolution properties between samples produced with different melt granulation parameters. NIRS is sensitive to changes in coating formulation, the quality of a coating excipient (hydroxypropyl methylcellulose), and coating time. In a concluding quantitative analysis, we demonstrate the feasibility of NIRS in a manufacturing context for predicting coating time and detecting production cores failing to meet dissolution test specifications.

Near infrared spectroscopy for qualitative comparison of pharmaceutical batches.

Pharmaceuticals are produced according to current pharmacopoeias, which require quality parameters. Tablets of identical formulation, produced by different factories should have the same properties before and after storage. In this article, we analyzed samples having two different origins before and after storage (30 degrees C, 75% relative moisture). The aim of the study is to propose two approaches to understand the differences between origins and the storage effect by near infrared spectroscopy. In the first part, the main wavelengths are identified in transmittance and reflectance near infrared spectra in order to identify the major differences between the samples. In this paper, this approach is called fingerprinting. In the second part, principal component analysis (PCA) is computed to confirm the fingerprinting interpretation. The two interpretations show the differences between batches: physical aspect and moisture content. The manufacturing process is responsible for the physical differences between batches. During the storage, changes are due to the increase of moisture content and the decrease of the active content.