Highly stable glasses of celecoxib: Influence on thermo-kinetic properties, microstructure and response towards crystal growth C. Rodríguez-Tinoco a , M. Gonzalez-Silveira a , J. Ràfols-Ribé a , G. Garcia a , J. Rodríguez-Viejo a,b, ⁎ a Grup de Nanomaterials i Microsistemes, Departament de Física, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain b MATGAS Research Centre, Campus UAB, 08193 Bellaterra, Spain abstract article info Article history: Received 28 May 2014 Received in revised form 21 July 2014 Accepted 23 July 2014 Available online xxxx Keywords: Ultrastable glasses; Glass transition; Crystallization; Celecoxib; Anisotropy Celecoxib, an anti-inflammatory drug widely used as a pharmaceutical product, is known for its poor ability to form a glass and its high tendency towards crystallization. Here, we report the preparation of vapor-deposited ultrastable glasses of Celecoxib with an onset temperature of the glass transition 20 K above its conventional value and a high thermodynamic stability. The time required for the loss of molecular anisotropy is 3 orders of magnitude higher than the time scales required for the alpha relaxation. We also report the influence of the stability of the glass on the surface crystallization at temperatures below the glass transition temperature. The growth of surface crystals is 30% faster in conventional glasses prepared from the liquid than in highly stable glasses. © 2014 Published by Elsevier B.V. 1. Introduction Pharmaceutical products are typically formed by crystalline drugs that are poorly water-soluble and show limited bioavailability [1]. On the contrary, amorphous forms show improved solubility [2]. However, their limited stability hinders widespread commercialization. Unfortu- nately, the amorphous state has higher energy than the crystalline state and may undergo crystallization during processing, storage and use of the product. Therefore, amorphous materials with enhanced stability could be the basis of a new generation of pharmaceutical drugs. Traditionally, the two ways to obtain very stable glasses were by reducing the cooling rate, though this approach is limited by the onset of crystallization, and by aging the glass at temperatures below the glass transition temperature, a very slow kinetical process. In addi- tion, crystallization can be activated if Johari-Goldstein relaxation mechanisms are active at the aging temperature [3]. Very recently, a new methodology to prepare highly stable glasses has emerged [4] and now it is well consolidated within the scientific community. This methodology employs physical vapor deposition at deposition temperatures slightly below the glass transition temperature, Tg, i.e. T dep = 0.8–0.9Tg, as a route to obtain thin film glasses with a re- markable enhancement of their kinetic and thermodynamic stability. Glasses grown in these conditions rival in stability with natural ambers aged during millions of years [5]. This behavior was initially observed for 1,3-bis-(1-naphthyl)-5-(2-naphthyl)benzene (TNB) [6] and indo- methacin (IMC) [4], but later on it has been corroborated for many other organic molecules such as toluene [7], ethylbenzene [7] or even mixtures of cis/trans-Decalin [8], in what seems to be a general trend for organic molecules [9]. This methodology has been successfully ex- tended to produce highly stable polymers [10] and metallic glasses [11,12]. Besides the enhancement in thermodynamic and kinetic stability, vapor-deposited ultrastable glasses exhibit other remarkable properties when compared to the conventional glass, such as higher thermal sta- bility [13], higher density [14], lower thermal expansion coefficient [15] and a growth front transformation mechanism into the liquid that initiates at free surfaces [16,17]. A striking property observed in thin film highly stable glasses of certain molecules is the existence of molecular anisotropy that produces a low-q extra peak in X-ray diffrac- tion patterns [18–20] and birefringence in ellipsometric experiments [14,15]. The primary goal of this paper is to analyze the feasibility of preparing highly stable glasses of a poor glass former such as celecoxib, CXIB. This molecule, largely used as a nonsteroidal anti-inflammatory drug, shows a prompt tendency to crystallization, inhibiting commercialization in the amorphous form [2]. We determine the kinetic and thermodynamic stability of the molecule by differential scanning calorimetry, DSC. Our results indicate that it is indeed possible to form ultrastable thin film glasses of this molecule and that the optimum substrate temperature is around 0.85 Tg, in agreement with a number of previous reports on other molecules [4]. We also use synchrotron X-ray diffraction to moni- tor the evolution of the anisotropic molecular packing during annealings Journal of Non-Crystalline Solids xxx (2014) xxx–xxx ⁎ Corresponding author at: Grup de Nanomaterials i Microsistemes, Departament de Física, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain. E-mail address: javier.rodriguez@uab.es (J. Rodríguez-Viejo). NOC-17041; No of Pages 6 http://dx.doi.org/10.1016/j.jnoncrysol.2014.07.031 0022-3093/© 2014 Published by Elsevier B.V. Contents lists available at ScienceDirect Journal of Non-Crystalline Solids journal homepage: www.elsevier.com/ locate/ jnoncrysol Please cite this article as: C. Rodríguez-Tinoco, et al., Highly stable glasses of celecoxib: Influence on thermo-kinetic properties, microstructure and response towards crystal growth, J. Non-Cryst. Solids (2014), http://dx.doi.org/10.1016/j.jnoncrysol.2014.07.031