International Journal of Pharmaceutics 419 (2011) 107–113 Contents lists available at ScienceDirect International Journal of Pharmaceutics jo ur nal homep a ge: www.elsevier.com/locate/ijpharm Characterization of melt extruded and conventional Isoptin formulations using Raman chemical imaging and chemometrics Balázs Vajna ∗ , Hajnalka Pataki, Zsombor Nagy, István Farkas, György Marosi Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budafoki út 8., H-1111 Budapest, Hungary a r t i c l e i n f o Article history: Received 7 February 2011 Received in revised form 14 July 2011 Accepted 15 July 2011 Available online 23 July 2011 Keywords: Micro-Raman Hyperspectral imaging Chemometrics Pharmaceutical MCR–ALS Extrusion a b s t r a c t Isoptin SR-E (Meltrex ® ) extruded tablets were assumed in a recent paper to be prepared with a compo- sition different from a conventional (Isoptin SR) formulation. This study reveals, however, using Raman mapping and chemometric evaluation, that in fact the same composition, comprising Na alginate as poly- mer matrix, is used in both products. It means that only the difference in the manufacturing technology causes the reported sustained release of verapamil hydrochloride even in ethanol containing dissolution media. The products are compared based on the obtained Raman chemical images, which allowed con- cluding in a new structure-based explanation for the differences in the dissolution profiles in the presence of ethanol. It is also shown that extrusion technology influences the dissolution profile effectively, even in the cases when solid solution is formed only partially. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Chemical imaging (CI) and chemometrics is a rapidly emerg- ing combination to characterize pharmaceutical products. This family of analytical methods couples a vibrational spectrometric (mid-infrared, near-infrared or Raman) technique with appropriate optics ( ˇ Saˇ si´ c, 2010), enabling the acquisition of visualized images of the samples containing chemical information. There are a vast number of combinations for the different spectrometric techniques and sampling methods (e.g. point-by-point mapping and global imaging), which are extensively described in numerous recent review papers (Gowen et al., 2008; Gendrin et al., 2008a; Amigo, 2010; Gordon and McGoverin, 2010). All CI techniques create sepa- rate vibrational spectra corresponding to each point of the analysed surface, the dataset of which is processed then to provide image of the spatial distribution of the components. When formulations under development or final products are subjects of such an analysis, a wide range of attributes can be char- acterized. Numerous solid dispersions have been studied, where the aim was to distribute the API homogeneously in a polymer matrix (Breitenbach et al., 1999; Nagy et al., 2010) and to keep the drug in stable amorphous phase (Docoslis et al., 2007; Karavas et al., 2007; Furuyama et al., 2008). The physical morphology of the active (or any other) ingredient in multicomponent formula- tions can be determined this way with high sensitivity (Lin et al., ∗ Corresponding author. Tel.: +36 1 463 5918; fax: +36 1 463 3648. E-mail address: balazs.vajna@gmail.com (B. Vajna). 2006). Most frequently the spatial distribution of a certain com- ponent is studied for troubleshooting of manufacturing processes (Clarke, 2004), monitoring blend homogeneity (Ravn et al., 2008) or to reveal the internal structure ( ˇ Saˇ si´ c et al., 2004; ˇ Saˇ si´ c, 2007) and understand the physical attributes of the products (Chan et al., 2003). Based on the spatial distribution of the ingredients, vari- ous formulations of the same composition can be compared (Vajna et al., 2010) and counterfeit products can be distinguished from the original (Puchert et al., 2010). The primary motivation of the present study arose on the basis of a recent paper published by Roth et al. (2009). The authors of the mentioned paper investigated the dissolution characteristics of different formulations containing verapamil hydrochloride, one of which was manufactured via melt extrusion (Meltrex ® ) technol- ogy. The extruded product, named Isoptin SR-E, was compared to the conventional sustained release Isoptin SR formulation. It was stated in the paper, that Isoptin SR-E (melt extruded) contained verapamil hydrochloride in a hydroxypropylcellulose (HPC) and hypromellose (HPMC) matrix, while Isoptin SR (sustained release) contained verapamil hydrochloride in a natrium-alginate retarding agent. This change in the excipients posed the most significant dif- ference between the two products. The SR-E formulation was found to keep its dissolution characteristics unchanged even in dissolu- tion media of high (40%) ethanol concentration, while the other conventional verapamil formulations (including Isoptin SR) lost their capability for sustained release under these circumstances. The aim we intended to achieve by the determination of the real composition of the extruded pharmaceutical, was two-fold: (1) to demonstrate the fact that the pure spectrum and the 0378-5173/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2011.07.023