International Journal of Pharmaceutics 460 (2014) 189–195 Contents lists available at ScienceDirect International Journal of Pharmaceutics j o ur nal ho me page: www.elsevier.com/locate/ijpharm Impact of differential surface molecular environment on the interparticulate bonding strength of celecoxib crystal habits Sameer R. Modi, Kailas S. Khomane, Arvind K. Bansal ∗ Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S. A. S. Nagar, Mohali, Punjab, India a r t i c l e i n f o Article history: Received 12 September 2013 Received in revised form 9 October 2013 Accepted 13 October 2013 Available online 20 October 2013 Keywords: Surface anisotropy Bonding strength Compactibility Crystal habits Milling Cleavage plane a b s t r a c t The present work investigates the impact of milling on differential compactibility behavior of celecoxib (CEL) crystal habits. Plate shaped (CEL-P) crystals showed better compactibility over acicular (CEL-A) crystals. Milling improved the compactibility of both the forms. However, despite similar particle shape, size, and surface area, milled fractions of the two habits showed significantly different interparticulate bonding strength. The greater bonding strength of milled CEL-P (MCEL-P) over milled CEL-A (MCEL- A) was attributed to the differential cleavage behavior of the two habits that conferred the different surface molecular environment to the milled powders. The preferred cleavage of CEL-P across {020} plane exposed the -CF 3 group and the methyl phenyl ring on the surface of MCEL-P. On the other hand, CEL-A preferentially fractured along their shortest axis that increased the exposure of {100} plane on the surface of MCEL-A, which exposed the -CF 3 group and the pyrazole ring. Surface free energy quantified by determining advancing contact angle revealed greater dispersive component of MCEL-P over MCEL-A. This is consistent with the differential cleavage behavior of CEL-P and CEL-A. This confirmed the role of dispersive component of surface free energy in governing interparticulate bonding strength of CEL. The study supports the postulate that tablet tensile strength is governed by the dispersive intermolecular interactions formed over the interparticulate bonding area. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Structure property relationship helps in designing a quality product. Successful tablet formulation development requires opti- mum tensile strength. Hence, it is important to understand material attributes that govern the tensile strength. Interparticulate bonding area and bonding strength contribute to the tablet tensile strength (Sun, 2011). Particle level properties like particle shape and particle size distribution are known to influence interparticulate bonding area (Patel et al., 2006). Interparticulate bonding strength is an inherent material prop- erty and is governed by intermolecular interactions (Sun, 2011). Among various bonding mechanism like solid bridge, intermolec- ular interactions, and mechanical interlocking, intermolecular interactions predominates in pharmaceutical materials (Nystrom et al., 1993). The dispersive (nonpolar) interactions, like van der Waals interactions, are isotropic in nature and are primarily respon- sible for particle–particle interactions (Derjaguin, 1960; Hiestand, ∗ Corresponding author. Tel.: +91 172 2214682 2126; fax: +91 172 2214692. E-mail address: akbansal@niper.ac.in (A.K. Bansal). 1997b; Israelachvili and Tabor, 1973). In contrast, polar inter- actions like hydrogen bonding, being anisotropic (directional) in nature, contribute least as only few atoms near the contact perime- ter would have the required spacing and juxtaposition (Hiestand, 1997a). Random particle reorientation during compaction further reduces the probability of these polar interactions. Recently, our group has reported correlationship between molecular packing density (true density) and interparticulate bonding strength of the pharmaceutical polymorphs (Khomane and Bansal, 2013a,b; Khomane et al., 2012, 2013; Upadhyay et al., 2013). Closed crystal packing (higher true density) offered greater number of isotropic molecular contacts. Few reports also corre- lated interparticulate bonding strength to the dispersive surface energy (van der Waals forces) of the materials (Chamarthy et al., 2009; Fichtner et al., 2008). Overall, tablet tensile strength is gov- erned by the dispersive intermolecular interactions formed over the interparticulate bonding area. Present work investigates the impact of milling on compactibil- ity of plate and acicular crystal habit of celecoxib (CEL) form III. The differential cleavage properties of the two crystal habits offered different chemical environment at the particle surface. This enabled us to study the contribution of differential surface 0378-5173/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ijpharm.2013.10.029