At-line monitoring of salification process of the antiretroviral lamivudine-saccharinate salt using FT-MIR spectroscopy with multivariate curve resolution

• Type: Article in International Scientific Journal
• Date: 2020

Authors

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

Journal

Title: Vibrational Spectroscopy

Vol. 106

ISSN: 0924-2031

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00R-D8Y

DOI: 10.1016/j.vibspec.2019.102992

Abstract (EN): This article presents a promising application of Fourier transform-mid infrared (FT-MIR) spectroscopy with multivariate curve resolution - alternating least-squares (MCR-ALS) as an at-line process analytical technology (PAT) to enhancing the understanding and continuous control of a pharmaceutical manufacturing process. Its objective was to monitor the synthesis of pharmaceutical multicomponent crystals in solid-state, namely the mixture between lamivudine (active pharmaceutical ingredient-API) and saccharin (coformer) using liquid assisted grinding (LAG) in proportion of 1:1 in a ball mill. The continuous monitoring of synthesis procedure ensured product quality, revealing some of the events that can be detected during mechanochemical synthesis by FT-MIR spectroscopy with MCR-ALS. The concentration profiles retrieved by MCR-ALS allowed to identify the end of the salt synthesis. In fact, this is one of the advantages of real-time monitoring using FT-MIR spectroscopy and MCR-ALS, because it can be helpful not only to monitor and control a pharmaceutical manufacturing process, but also to optimize efficient use of energy, time and raw materials for lamivudine-saccharinate salt synthesis. Moreover, it allowed to understand that the antiretroviral lamivudine-saccharinate salt synthetized by LAG showed a fast reaction mechanism due to the presence of ethanol as catalyst. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) techniques provided additional information needed to fully characterize pharmaceutical lamivudine-saccharinate salt synthetized by LAG technique.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7