Development of a Near Infrared Spectroscopy method for the in-line quantitative bilastine drug determination during pharmaceutical powders blending

Diletta Biagi; Paolo Nencioni; Maurizio Valleri; Niccolò Calamassi; Paola Mura

doi:10.1016/j.jpba.2021.114277

Development of a Near Infrared Spectroscopy method for the in-line quantitative bilastine drug determination during pharmaceutical powders blending

J Pharm Biomed Anal. 2021 Sep 10:204:114277. doi: 10.1016/j.jpba.2021.114277. Epub 2021 Jul 22.

Authors

Diletta Biagi¹, Paolo Nencioni², Maurizio Valleri², Niccolò Calamassi³, Paola Mura⁴

Affiliations

¹ Menarini Manufacturing Logistic and Services s.r.l. (AMMLS), Via dei Sette Santi 1/3, 50131, Florence, Italy; Department of Chemistry, University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Florence, Italy. Electronic address: diletta.biagi@unifi.it.
² Menarini Manufacturing Logistic and Services s.r.l. (AMMLS), Via dei Sette Santi 1/3, 50131, Florence, Italy.
³ Department of Pharmaceutical Sciences, University of Perugia, via del Liceo 1, 06123, Perugia, Italy.
⁴ Department of Chemistry, University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Florence, Italy.

PMID: 34332309
DOI: 10.1016/j.jpba.2021.114277

Abstract

The Food and Drug Administration (FDA)'s guidelines and the Process Analytical Technology (PAT) approach conceptualize the idea of real time monitoring of a process, with the primary objective of improvement of quality and also of time and resources saving. New instruments are needed to perform an efficient PAT process control and Near Infrared Spectroscopy (NIRS), thanks to its rapid and drastic development of last years, could be a very good choice, in virtue of its high versatility, speed of analysis, non-destructiveness and absence of sample chemical treatment. This work was aimed to develop a NIR analytical method for bilastine assay in powder mixtures for direct compression. In particular, the use of NIR instrumentation should allow to control the bilastine concentration and the whole blending process, assuring the achievement of a homogeneous blend. The commercial tablet formulation of bilastine was particularly suitable for this purpose, due to its simple composition (four excipients) and direct compression manufacturing process. Calibration and validation set were prepared according to a Placket-Burman experimental design and acquired with a miniaturized NIR in-line instrument (MicroNIR by Viavi Solution Inc.). Chemometric was applied to optimize information extraction from spectra, by subjecting them to a Standard Normal Variate (SNV) and a Savitzky-Golay second derivative pre-treatment. This spectra pre-treatment, combined with the most suitable wavelength interval (resulted between 1087 and 1217 nm), enabled to obtain a Partial Least Square (PLS) model with a good predictive ability. The selected model, tried on laboratory and production batches, provided in both cases good assay predictions. Results were confirmed by traditional HPLC (High Performance Liquid Chromatography) API (Active Pharmaceutical Ingredient) content uniformity test on the final product.

Keywords: Bilastine; Chemometric; Near Infrared Spectroscopy; Process Analytical Technology (PAT); Quantitative analysis; Spectra pre-treatment.

MeSH terms

Benzimidazoles
Calibration
Drug Compounding
Least-Squares Analysis
Piperidines
Powders
Research Design
Spectroscopy, Near-Infrared*
Tablets
Technology, Pharmaceutical*

Substances

Benzimidazoles
Piperidines
Powders
Tablets
bilastine