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Molecules 2016, 21(4), 509;

Properties of the Sodium Naproxen-Lactose-Tetrahydrate Co-Crystal upon Processing and Storage

Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
Author to whom correspondence should be addressed.
Academic Editor: Sohrab Rohani
Received: 21 March 2016 / Revised: 8 April 2016 / Accepted: 11 April 2016 / Published: 19 April 2016
(This article belongs to the Special Issue Crystallization of Pharmaceuticals)
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Co-crystals and co-amorphous systems are two strategies to improve the physical properties of an active pharmaceutical ingredient and, thus, have recently gained considerable interest both in academia and the pharmaceutical industry. In this study, the behavior of the recently identified sodium naproxen-lactose-tetrahydrate co-crystal and the co-amorphous mixture of sodium, naproxen, and lactose was investigated. The structure of the co-crystal is described using single-crystal X-ray diffraction. The structural analysis revealed a monoclinic lattice, space group P21, with the asymmetric unit containing one molecule of lactose, one of naproxen, sodium, and four water molecules. Upon heating, it was observed that the co-crystal transforms into a co-amorphous system due to the loss of its crystalline bound water. Dehydration and co-amorphization were studied using synchrotron X-ray radiation and thermogravimetric analysis (TGA). Subsequently, different processing techniques (ball milling, spray drying, and dehydration) were used to prepare the co-amorphous mixture of sodium, naproxen, and lactose. X-ray powder diffraction (XRPD) revealed the amorphous nature of the mixtures after preparation. Differential scanning calorimetry (DSC) analysis showed that the blends were single-phase co-amorphous systems as indicated by a single glass transition temperature. The samples were subsequently tested for physical stability under dry (silica gel at 25 and 40 °C) and humid conditions (25 °C/75% RH). The co-amorphous samples stored at 25 °C/75% RH quickly recrystallized into the co-crystalline state. On the other hand, the samples stored under dry conditions remained physically stable after five months of storage, except the ball milled sample stored at 40 °C which showed signs of recrystallization. Under these dry conditions, however, the ball-milled co-amorphous blend crystallized into the individual crystalline components. View Full-Text
Keywords: co-crystal 1; co-amorphous 2; dehydration 3 co-crystal 1; co-amorphous 2; dehydration 3

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Sovago, I.; Wang, W.; Qiu, D.; Raijada, D.; Rantanen, J.; Grohganz, H.; Rades, T.; Bond, A.D.; Löbmann, K. Properties of the Sodium Naproxen-Lactose-Tetrahydrate Co-Crystal upon Processing and Storage. Molecules 2016, 21, 509.

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