Critical review of near-infrared spectroscopic methods validations in pharmaceutical applications.
ABSTRACT Based on the large number of publications reported over the past five years, near-infrared spectroscopy (NIRS) is more and more considered an attractive and promising analytical tool regarding Process Analytical Technology and Green Chemistry. From the reviewed literature, few of these publications present a thoroughly validated NIRS method even if some guidelines have been published by different groups and regulatory authorities. However, as any analytical method, the validation of NIRS method is a mandatory step at the end of the development in order to give enough guarantees that each of the future results during routine use will be close enough to the true value. Besides the introduction of PAT concepts in the revised document of the European Pharmacopoeia (2.2.40) dealing with near-infrared spectroscopy recently published in Pharmeuropa, it agrees very well with this mandatory step. Indeed, the latter suggests to use similar analytical performance characteristics than those required for any analytical procedure based on acceptance criteria consistent with the intended use of the method. In this context, this review gives a comprehensive and critical overview of the methodologies applied to assess the validity of quantitative NIRS methods used in pharmaceutical applications.
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ABSTRACT: Abstract Context: Near-Infrared (NIR) spectroscopy is an important component of a Process Analytical Technology (PAT) toolbox and is a key technology for enabling the rapid analysis of pharmaceutical tablets. Objective: The aim of this research work was to develop and validate NIR-chemometric methods not only for the determination of active pharmaceutical ingredients content but also pharmaceutical properties (crushing strength, disintegration time) of meloxicam tablets. Materials and methods: The development of the method for active content assay was performed on samples corresponding to 80%, 90%, 100%, 110% and 120% of meloxicam content and the development of the methods for pharmaceutical characterization was performed on samples prepared at seven different compression forces (ranging from 7 to 45 kN) using NIR transmission spectra of intact tablets and PLS as a regression method. Results: The results show that the developed methods have good trueness, precision and accuracy and are appropriate for direct active content assay in tablets (ranging from 12 to 18 mg/tablet) and also for predicting crushing strength and disintegration time of intact meloxicam tablets. Discussion: The comparative data show that the proposed methods are in good agreement with the reference methods currently used for the characterization of meloxicam tablets (HPLC-UV methods for the assay and European Pharmacopeia methods for determining the crushing strength and disintegration time). Conclusion: The results show the possibility to predict both chemical properties (active content) and physical/pharmaceutical properties (crushing strength and disintegration time) directly, without any sample preparation, from the same NIR transmission spectrum of meloxicam tablets.Drug Development and Industrial Pharmacy 04/2013; · 1.54 Impact Factor
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ABSTRACT: This paper describes the development, validation and application of NIR-chemometric methods for API content and pharmaceutical characterization (disintegration time and crushing strength) of indapamide intact tablets. Development of the method for chemical characterization was performed on samples corresponding to 80, 90, 100, 110 and 120% of indapamide content and for pharmaceutical characterization on samples prepared at nine different compression forces (covering the interval 7-45kN). NIR spectra of prepared tablets were recorded in transmission mode, and partial least-squares followed by leave-one-out cross-validation were used to develop models for the prediction of the drug content and the pharmaceutical properties of tablets. All developed models were validated in terms of trueness, precision and accuracy. No statistical differences were found between results predicted by NIR-chemometric methods and the ones determined by reference methods. Therefore, the developed NIR-chemometric methods meet the requirements of a high-throughput method for the determination of drug content, pharmaceutical properties of indapamide tablets.Journal of pharmaceutical and biomedical analysis 12/2012; · 2.45 Impact Factor
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ABSTRACT: Pharmaceutical companies are progressively adopting and introducing Process Analytical Technology (PAT) and Quality-by-Design (QbD) concepts promoted by the regulatory agencies, aiming the building of the quality directly into the product by combining thorough scientific understanding and quality risk management. An analytical method based on near infrared (NIR) spectroscopy was developed as a PAT tool to control on-line an API (active pharmaceutical ingredient) manufacturing crystallization step during which the API and residual solvent contents need to be precisely determined to reach the predefined seeding point. An original methodology based on the QbD principles was designed to conduct the development and validation of the NIR method and to ensure that it is fitted for its intended use. On this basis, Partial least squares (PLS) models were developed and optimized using chemometrics methods. The method was fully validated according to the ICH Q2(R1) guideline and using the accuracy profile approach. The dosing ranges were evaluated to 9.0–12.0% w/w for the API and 0.18–1.50% w/w for the residual methanol. As by nature the variability of the sampling method and the reference method are included in the variability obtained for the NIR method during the validation phase, a real-time process monitoring exercise was performed to prove its fit for purpose. The implementation of this in-process control (IPC) method on the industrial plant from the launch of the new API synthesis process will enable automatic control of the final crystallization step in order to ensure a predefined quality level of the API. In addition, several valuable benefits are expected including reduction of the process time, suppression of a rather difficult sampling and tedious off-line analyses.Talanta 01/2014; 120:114–125. · 3.50 Impact Factor
De Bleye C, Chavez P.-F., Mantanus J., Marini R., Hubert Ph., Rozet E.,
Ziemons E., Critical review of Near-infrared spectroscopic methods
validations in pharmaceutical applications, Journal of Pharmaceutical and
Biomedical Analysis 69, 2012, 125-132.
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