At-line green synthesis monitoring of new pharmaceutical co-crystals lamivudine:theophylline polymorph I and II, quantification of polymorph I among its APIs using FT-IR spectroscopy and MCR-ALS

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Mazivila, SJ (Author) Other; Castro, RAE (Author) Other; Leitao, JMM (Author) Other; Joaquim C G E Esteves da Silva (Author) FCUP

Journal

Title: Journal of Pharmaceutical and Biomedical Analysis

Vol. 169

Pages: 235-244

ISSN: 0731-7085

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 12 Citations

Other information

Authenticus ID: P-00Q-G0Z

DOI: 10.1016/j.jpba.2019.03.014

Abstract (EN): This paper, reports for the first time the green synthesis of the polymorphs I and II of new pharmaceutical co-crystals lamivudine:theophylline in solid-phase, through the mixture between lamivudine and theophylline (both active pharmaceutical ingredients-APIs) in the proportion of 1:1 by neat grinding and liquid assisted grinding (10 mu L ethanol). Fourier transform-infrared (FT-IR) spectroscopy and multivariate curve resolution with alternating least-squares (MCR-ALS) were employed as non-invasive analytical methodology for the at-line green synthesis monitoring of the novels lamivudine:theophylline co-crystals. By MCR-ALS it was possible to identify each component present in a complex matrix, with strong spectral overlapping, containing lamivudine, theophylline, and the novel lamivudine:theophylline co-crystal with high confidence based on the comparison of the pure and recovered spectral and concentration profiles. This model allowed to identify the end of the reaction and understand the mechanism involved in the synthesis through the identification of the intermediates present in the synthesis process. Also, MCR-ALS model estimated the concentration of co-crystal polymorph I with a root mean square error of prediction (RMSEP) and the percentage relative error of prediction (REP%) equal to 3.323 (w/w) and 9.9%, respectively. These were good results since the spectral profile of cocrystal and the physical mixture of its APIs present strong spectral overlapping in their spectral domain. Therefore, the quantification of the co-crystal between its APIs (lamivudine and theophylline) certified that the co-crystal as final product was obtained, collaborating with the results obtained by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10