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Characterization of Cimetidine–Piroxicam Coprecipitate Interaction Using Experimental Studies and Molecular Dynamic Simulations

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Abstract

The crystalline states of cimetidine and piroxicam, when coprecipitated from solvents containing 1:1 mole ratio, were transformed to amorphous states as observed using powder X-ray diffraction (PXRD). Amorphous forms of drugs generally exhibit higher water solubility than crystalline forms. It is therefore interesting to investigate the interactions that cause the transformation of both the crystalline drugs. Intermolecular interactions between the drugs were determined using Fourier-transform infrared spectroscopy (FTIR) and solid-state 13C CP/MAS NMR. Molecular dynamic (MD) simulation was performed for the first time for this type of study to indicate the specific groups involved in the interactions based on radial distribution function (RDF) analyses. RDF is a useful tool to describe the average density of atoms at a distance from a specified atom. FTIR spectra revealed a shift of the C≡N stretching band of cimetidine. The 13C CP/MAS NMR spectra indicated downfield shifts of C11, C15 and C7 of piroxicam. RDF analyses indicated that intermolecular interactions occurred between the amide oxygen atom as well as the pyridyl nitrogen of piroxicam and H-N3 of cimetidine. The hydrogen atom (O–H) at C7 interacts with the N1 of cimetidine. Since the MD simulation results are consistent with, and complementary to the experimental analyses, such simulations could provide a novel strategy for investigating specific interacting groups of drugs in coprecipitates, or in amorphous mixtures.

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Acknowledgments

This work was supported by Prince of Songkla University, PSU-Grid and the National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Ministry of Science and Technology through its National Nanoscience Consortium (CNC). The authors would like to thank Professor Terrence Cosgrove and Dr. Youssef Espidel for 13C CP/MAS NMR experiments.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand

    Vimon Tantishaiyakul & Krit Suknuntha

  2. School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand

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  1. Vimon Tantishaiyakul
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  2. Krit Suknuntha
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Correspondence to Vimon Tantishaiyakul.

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Tantishaiyakul, V., Suknuntha, K. & Vao-Soongnern, V. Characterization of Cimetidine–Piroxicam Coprecipitate Interaction Using Experimental Studies and Molecular Dynamic Simulations. AAPS PharmSciTech 11, 952–958 (2010). https://doi.org/10.1208/s12249-010-9461-5

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  • DOI: https://doi.org/10.1208/s12249-010-9461-5

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