Studying of crystal growth and overall crystallization of naproxen from binary mixtures

E Kaminska; O Madejczyk; M Tarnacka; K Jurkiewicz; K Kaminski; M Paluch

doi:10.1016/j.ejpb.2016.12.014

Studying of crystal growth and overall crystallization of naproxen from binary mixtures

Eur J Pharm Biopharm. 2017 Apr:113:75-87. doi: 10.1016/j.ejpb.2016.12.014. Epub 2016 Dec 27.

Authors

E Kaminska¹, O Madejczyk², M Tarnacka², K Jurkiewicz², K Kaminski², M Paluch²

Affiliations

¹ Department of Pharmacognosy and Phytochemistry, Medical University of Silesia in Katowice, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, ul. Jagiellonska 4, 41-200 Sosnowiec, Poland. Electronic address: ekaminska@sum.edu.pl.
² Institute of Physics, University of Silesia in Katowice, ul. Uniwersytecka 4, 40-007 Katowice, Poland; Silesian Center for Education and Interdisciplinary Research, University of Silesia, ul. 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.

PMID: 28034808
DOI: 10.1016/j.ejpb.2016.12.014

Abstract

Broadband dielectric spectroscopy (BDS) and differential scanning calorimetry (DSC) were applied to investigate the molecular dynamics and phase transitions in binary mixtures composed of naproxen (NAP) and acetylated saccharides: maltose (acMAL) and sucrose (acSUC). Moreover, the application of BDS method and optical microscopy enabled us to study both crystallization kinetics and crystal growth of naproxen from the solid dispersions with the highest content of modified carbohydrates (1:5wt ratio). It was found that the activation barriers of crystallization estimated from dielectric measurements are completely different for both studied herein mixtures. Much higher E_a (=205kJ/mol) was obtained for NAP-acMAL solid dispersion. It is probably due to simultaneous crystallization of both components of the mixture. On the other hand, lower value of E_a in the case of NAP-acSUC solid dispersion (81kJ/mol) indicated, that naproxen is the only crystallizing compound. This hypothesis was confirmed by X-ray diffraction studies. We also suggested that specific intermolecular dipole-dipole interactions between active substance and excipient may be an alternative explanation for the difference between activation barrier obtained for NAP-acMAL and NAP-acSUC binary mixtures. Furthermore, optical measurements showed that the activation energy for crystal growth of naproxen increases in binary mixtures. They also revealed that both excipients: acMAL and acSUC move the temperature of the maximum of crystal growth towards lower temperatures. Interestingly, this maximum occurs for nearly the same structural relaxation time, which is a good approximation of viscosity, for all samples. Finally, it was also noticed that although naproxen crystallizes to the same polymorphic form in both systems, there are some differences in morphology of obtained crystals. Thus, the observed behavior may have a significant impact on the bioavailability and dissolution rate of API produced in that way.

Keywords: Acetylated disaccharides; Crystal growth; Kinetics of crystallization; Molecular dynamics; Naproxen.

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / chemistry*
Calorimetry, Differential Scanning
Crystallization
Crystallography, X-Ray
Kinetics
Naproxen / chemistry*

Substances

Anti-Inflammatory Agents, Non-Steroidal
Naproxen