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The Scientific World Journal
Volume 2014 (2014), Article ID 248651, 13 pages
http://dx.doi.org/10.1155/2014/248651
Research Article

Design, Synthesis, and In Vitro Kinetics Study of Atenolol Prodrugs for the Use in Aqueous Formulations

1Faculty of Pharmacy, Al-Quds University, P.O. Box 20002, Jerusalem, Palestine
2Department of Sciences, University of Basilicata, Via dell’Ateneo Lucano 10, 85100 Potenza, Italy
3Faculty of Public Health Sciences, Al-Quds University, P.O. Box 20002, Jerusalem, Palestine

Received 10 October 2013; Accepted 1 December 2013; Published 12 January 2014

Academic Editors: R. I. Cukier, E. Gomez-Bengoa, R. Luo, D. Quintanar-Guerrero, and T. Takayanagi

Copyright © 2014 Rafik Karaman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. G. K. McEvoy, AHFS Drug Information 93, American Society of Health System Pharmacists, 1993.
  2. http://homepage.ntlworld.com/bhandari/Imperial/Atenolol/Synthesis.htm.
  3. A. Melander, P. Stenberg, and H. Liedholm, “Food-induced reduction in bioavailability of atenolol,” European Journal of Clinical Pharmacology, vol. 16, no. 5, pp. 327–330, 1979. View at Google Scholar · View at Scopus
  4. J. McAinsh, W. T. Simpson, and B. F. Holmes, “Bioavailability of atenolol formulations,” Biopharmaceutics and Drug Disposition, vol. 1, no. 6, pp. 323–332, 1980. View at Google Scholar · View at Scopus
  5. J. F. Standing and C. Tuleu, “Paediatric formulations—getting to the heart of the problem,” International Journal of Pharmaceutics, vol. 300, no. 1-2, pp. 56–66, 2005. View at Publisher · View at Google Scholar · View at Scopus
  6. S. S. Garner, D. B. Wiest, and E. R. Reynolds Jr., “Stability of atenolol in an extemporaneously compounded oral liquid,” American Journal of Hospital Pharmacy, vol. 51, no. 4, pp. 508–511, 1994. View at Google Scholar · View at Scopus
  7. T. Foppa, F. S. Murakami, and M. A. S. Silva, “Development, validation and stability study of pediatric atenolol syrup,” Pharmazie, vol. 62, no. 7, pp. 519–521, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. D. Patel, D. H. Doshi, and A. Desia, “Short term stability of atenolol in oral liquid formulations,” International Journal of Pharmaceutical Compounding, vol. 1, no. 6, pp. 437–439, 1997. View at Google Scholar
  9. K. Chan and J. Swenden, “Pilot study of the short-term physico-chemical stability of atenolol tablets stored in a multi-compartment compliance aid,” European Journal of Hospital Pharmacy, vol. 13, pp. 60–66, 2007. View at Google Scholar
  10. R. Karaman, K. Dajani, and H. Hallak, “Computer-assisted design for atenolol prodrugs for the use in aqueous formulations,” Journal of Molecular Modeling, vol. 18, pp. 1523–1540, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. B. Anroop, B. Ghosh, V. Parcha, and J. Khanam, “Transdermal delivery of atenolol: effect of prodrugs and iontophoresis,” Current Drug Delivery, vol. 6, no. 3, pp. 280–290, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. H. Sohi, Y. Sultana, and R. K. Khar, “Taste masking technologies in oral pharmaceuticals: recent developments and approaches,” Drug Development and Industrial Pharmacy, vol. 30, no. 5, pp. 429–448, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. W. J. Reilly, “Pharmaceutical necessities,” in Remington: The Science and Practice of Pharmacy, pp. 1018–1020, Mack Publishing Company, 2002. View at Google Scholar
  14. A. A. Fawzy, “Pleasant-tasting aqueous liquid composition of a bitter-tasting drug,” PCT International Applications, WO 1998005312 A1, 1998.
  15. W. G. Gowan, “Aliphatic esters as a solventless coating for pharmaceuticals,” Patent CA 2082137 C, 1993.
  16. K. Gowthamarajan, G. T. Kulkarni, and M. N. Kumar, “Pop the pills without bitterness: taste-masking technologies for bitter drugs,” Resonance, vol. 9, no. 12, pp. 25–32, 2004. View at Publisher · View at Google Scholar
  17. J. A. Bakan, “Microencapsulation,” in Theory and Practice of Industrial Pharmacy, pp. 412–429, 3rd edition, 1986. View at Google Scholar
  18. V. S. Iyer and S. C. Srinivas, “Effervescent granular formulations of antiretroviral drugs,” Patent WO2007060682, 2007.
  19. L. Bush, “Bitter taste bypass need for sugar spoon,” Pharm Technol, 2004, http://www.pharmtech.com/pharmtech/data/articlestandard//pharmtech/072004/84521/article.pdf.
  20. “Ion exchange resin complexes: an approach to mask the taste of bitter drugs,” http://www.pharmainfo.net/reviews/ion-exchange-resin-complexes-approach-mask-taste-bitter-drugs.
  21. W. S. Bress, N. Kulkarni, S. Ambike, and M. P. Ramsay, “Fast dissolving orally consumable filsm containing an ion exchange resin as a taste masking agent,” Patent EP1674078, 2006.
  22. W. R. Mendes, Theory and Practice of Industrial Pharmacy, 3rd edition, 1976.
  23. A. M. J. Redondo and L. B. Abanades, “Aqueous base liquid pharmaceutical compositions in suspension form for the oral administration of ibuprofen,” Patent WO 047550, 2003.
  24. N. Kashid, P. Chouhan, and G. Mukherji, “Taste masked pharmaceutical composition for oral solid dosage form and process for preparing the same using magnesium aluminium silicate,” Patent WO2007108010, 2007.
  25. H. Hejaz, R. Karaman, and M. Khamis, “Computer-assisted design for paracetamol masking bitter taste prodrugs,” Journal of Molecular Modeling, vol. 18, no. 1, pp. 103–114, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. S. C. Shin and J. S. Choi, “Enhanced bioavailability of atenolol by transdermal administration of the ethylene-vinyl acetate matrix in rabbits,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 56, no. 3, pp. 439–443, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. A. C. Montes-Gil, M. Zanfolin, C. E. Okuyama et al., “Pharmacokinetic profile of atenolol aspirinate,” Archiv der Pharmazie, vol. 340, no. 9, pp. 445–455, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. V. J. Stella, “Prodrugs as therapeutics,” Expert Opinion on Therapeutic Patents, vol. 14, no. 3, pp. 277–280, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. V. J. Stella, “Prodrugs: some thoughts and current issues,” Journal of Pharmaceutical Sciences, vol. 99, no. 12, pp. 4755–4765, 2010. View at Publisher · View at Google Scholar
  30. K. M. Huttunen, H. Raunio, and J. Rautio, “Prodrugs-from serendipity to rational design,” Pharmacological Reviews, vol. 63, no. 3, pp. 750–771, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. V. J. Stella, R. T. Borchardt, M. Hageman, R. Oliyai, H. Maag, and J. Tilley, Prodrugs: challenges and Rewards Part 1 and Part 2, Springer, New York, NY, USA, 2007. View at Publisher · View at Google Scholar
  32. V. J. Stella, W. N. A. Charman, and V. H. Naringrekar, “Prodrugs. Do they have advantages in clinical practice?” Drugs, vol. 29, no. 5, pp. 455–473, 1985. View at Google Scholar · View at Scopus
  33. P. K. Banerjee and G. L. Amidon, “Design of prodrugs based on enzymes substrate specificity,” in Design of Prodrugs, pp. 93–133, 1985. View at Google Scholar
  34. C. E. Müller, “Prodrug approaches for enhancing the bioavailability of drugs with low solubility,” Chemistry and Biodiversity, vol. 6, no. 11, pp. 2071–2083, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. R. G. Parr and W. Yang, Density Functional Theory of Atoms and Molecules, Oxford University Press, Oxford, UK, 1989.
  36. U. Burker and N. L. Allinger, Molecular Mechanics, American Chemical Society, Washington, DC, USA, 1982.
  37. A. Warshel and M. Levitt, “Theoretical studies of enzymatic reactions: dielectric, electrostatic and steric stabilization of the carbonium ion in the reaction of lysozyme,” Journal of Molecular Biology, vol. 103, no. 2, pp. 227–249, 1976. View at Google Scholar · View at Scopus
  38. A. J. Kirby and P. W. Lancaster, “Structure and efficiency in intramolecular and enzymic catalysis. Catalysis of amide hydrolysis by the carboxy-group of substituted maleamic acids,” Journal of the Chemical Society, Perkin Transactions 2, no. 9, pp. 1206–1214, 1972. View at Google Scholar · View at Scopus
  39. R. Karaman, “Analyzing the efficiency in intramolecular amide hydrolysis of Kirby's N-alkylmaleamic acids—a computational approach,” Computational and Theoretical Chemistry, vol. 974, no. 1–3, pp. 133–142, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. S. E. Barber, K. E. S. Dean, and A. J. Kirby, “A mechanism for efficient proton-transfer catalysis. Intramolecular general acid catalysis of the hydrolysis of 1-arylethyl ethers of salicylic acid,” Canadian Journal of Chemistry, vol. 77, no. 5-6, pp. 792–801, 1999. View at Google Scholar · View at Scopus
  41. A. J. Kirby, M. F. Lima, D. da Silva, C. D. Roussev, and F. Nome, “Efficient intramolecular general acid catalysis of nucleophilic attack on a phosphodiester,” Journal of the American Chemical Society, vol. 128, no. 51, pp. 16944–16952, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. A. J. Kirby and N. H. Williams, “Efficient intramolecular general acid catalysis of enol ether hydrolysis. Hydrogen-bonding stabilization of the transition state for proton transfer to carbon,” Journal of the Chemical Society, Perkin Transactions 2, vol. 2, pp. 643–648, 1994. View at Publisher · View at Google Scholar
  43. A. J. Kirby and N. H. Williams, “Efficient intramolecular general acid catalysis of vinyl ether hydrolysis by the neighbouring carboxylic acid group,” Journal of the Chemical Society D, no. 22, pp. 1643–1644, 1991. View at Publisher · View at Google Scholar · View at Scopus
  44. A. J. Kirby, “Enzyme Mechanisms, Models, and Mimics,” Angewandte Chemie, vol. 35, no. 7, pp. 707–724, 1996. View at Google Scholar · View at Scopus
  45. T. H. Fife and T. J. Przystas, “Intramolecular general acid catalysis in the hydrolysis of acetals with aliphatic alcohol leaving groups,” Journal of the American Chemical Society, vol. 101, no. 5, pp. 1202–1210, 1979. View at Google Scholar · View at Scopus
  46. A. J. Kirby, “Efficiency of proton transfer catalysis in models and enzymes,” Accounts of Chemical Research, vol. 30, no. 7, pp. 290–296, 1997. View at Google Scholar · View at Scopus
  47. R. Karaman, “The efficiency of proton transfer in Kirby's enzyme model, a computational approach,” Tetrahedron Letters, vol. 51, no. 16, pp. 2130–2135, 2010. View at Publisher · View at Google Scholar · View at Scopus
  48. R. Karaman, “The effective molarity (EM) puzzle in proton transfer reactions,” Bioorganic Chemistry, vol. 37, no. 4, pp. 106–110, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. F. M. Menger and M. Ladika, “Fast hydrolysis of an aliphatic amide at neutral pH and ambient temperature. A peptidase model,” Journal of the American Chemical Society, vol. 110, no. 20, pp. 6794–6796, 1988. View at Google Scholar · View at Scopus
  50. F. M. Menger, “On the source of intramolecular and enzymatic reactivity,” Accounts of Chemical Research, vol. 18, no. 5, pp. 128–134, 1985. View at Google Scholar · View at Scopus
  51. F. M. Menger, J. F. Chow, H. Kaiserman, and P. C. Vasquez, “Directionality of proton transfer in solution. Three systems of known angularity,” Journal of the American Chemical Society, vol. 105, no. 15, pp. 4996–5002, 1983. View at Google Scholar · View at Scopus
  52. F. M. Menger, A. L. Galloway, and D. G. Musaev, “Relationship between rate and distance,” Chemical Communications, vol. 9, no. 18, pp. 2370–2371, 2003. View at Google Scholar · View at Scopus
  53. R. Karaman, “Analysis of Menger's 'spatiotemporal hypothesis',” Tetrahedron Letters, vol. 49, no. 41, pp. 5998–6002, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. S. Milstien and L. A. Cohen, “Concurrent general-acid and general-base catalysis of esterification,” Journal of the American Chemical Society, vol. 92, no. 14, pp. 4377–4382, 1970. View at Google Scholar · View at Scopus
  55. S. Milstien and L. A. Cohen, “Rate acceleration by stereopopulation control: models for enzyme action,” Proceedings of the National Academy of Sciences of the United States of America, vol. 67, no. 3, pp. 1143–1147, 1970. View at Google Scholar · View at Scopus
  56. S. Milstien and L. A. Cohen, “Stereopopulation control. I. Rate enhancement in the lactonizations of o-hydroxyhydrocinnamic acids,” Journal of the American Chemical Society, vol. 94, no. 26, pp. 9158–9165, 1972. View at Google Scholar · View at Scopus
  57. R. Karaman, “Proximity vs. strain in intramolecular ring-closing reactions,” Molecular Physics, vol. 108, no. 13, pp. 1723–1730, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. R. F. Brown and N. M. van Gulick, “The geminal alkyl effect on the rates of ring closure of bromobutylamines,” Journal of Organic Chemistry, vol. 21, no. 9, pp. 1046–1049, 1956. View at Google Scholar · View at Scopus
  59. T. C. Bruice and U. K. Pandit, “The effect of geminal substitution ring size and rotamer distribution on the intra molecular nucleophilic catalysis of the hydrolysis of monophenyl esters of dibasic acids and the solvolysis of the intermediate anhydrides,” Journal of the American Chemical Society, vol. 82, no. 22, pp. 5858–5865, 1960. View at Publisher · View at Google Scholar
  60. T. C. Bruice and U. K. Pandit, “Intramolecular models depicting the kinetic importance of “Fit” in enzymatic catalysis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 46, pp. 402–404, 1960. View at Publisher · View at Google Scholar
  61. C. Galli and L. Mandolini, “The role of ring strain on the ease of ring closure of bifunctional chain molecules,” European Journal of Organic Chemistry, no. 18, pp. 3117–3125, 2000. View at Google Scholar · View at Scopus
  62. R. Karaman, “Prodrugs of aza nucleosides based on proton transfer reaction,” Journal of Computer-Aided Molecular Design, vol. 24, no. 12, pp. 961–970, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. R. Karaman, W. Amly, S. A. Bufo, and L. Scrano, “Computationally designed prodrugs of statins based on Kirby's enzyme model,” Journal of Molecular Modeling, vol. 19, no. 9, pp. 3969–3982, 2013. View at Publisher · View at Google Scholar
  64. R. Karaman, D. Karaman, and I. Zeiadeh, “Computationally-designed phenylephrine prodrugs—a model for enhancing bioavailability,” Molecular Physics, vol. 111, no. 21, pp. 3249–3264, 2013. View at Publisher · View at Google Scholar
  65. R. Karaman, H. Ghareeb, K. K. Dajani et al., “Design, synthesis and in-vitro kinetic study of tranexamic acid prodrugs for the treatment of bleeding conditions,” Journal of Computer-Aided Molecular Design, vol. 27, no. 7, pp. 615–635, 2013. View at Publisher · View at Google Scholar
  66. R. Karaman, K. K. Dajani, A. Qtait, and M. Khamis, “Prodrugs of acyclovir—a computational approach,” Chemical Biology and Drug Design, vol. 79, no. 5, pp. 819–834, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. R. Karaman, “Prodrugs for masking bitter taste of antibacterial drugs—a computational approach,” Journal of Molecular Modeling, vol. 19, no. 6, pp. 2399–2412, 2013. View at Publisher · View at Google Scholar
  68. R. Karaman, “Computational-aided design for dopamine prodrugs based on novel chemical approach,” Chemical Biology and Drug Design, vol. 78, no. 5, pp. 853–863, 2011. View at Publisher · View at Google Scholar · View at Scopus
  69. Y. Zhao and D. G. Truhlar, “Density functionals with broad applicability in chemistry,” Accounts of Chemical Research, vol. 41, no. 2, pp. 157–167, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. Y. Zhao and D. G. Truhlar, “Exploring the limit of accuracy of the global hybrid meta density functional for main-group thermochemistry, kinetics, and noncovalent interactions,” Journal of Chemical Theory and Computation, vol. 4, no. 11, pp. 1849–1868, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. J. Zheng, Y. Zhao, and D. G. Truhlar, “The DBH24/08 database and its use to assess electronic structure model chemistries for chemical reaction barrier heights,” Journal of Chemical Theory and Computation, vol. 5, no. 4, pp. 808–821, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. M. J. Frisch, G. W. Trucks, H. B. Schlegel et al., Gaussian 09, Revision A.1, Gaussian Inc., Wallingford, Conn, USA, 2009.
  73. C. J. Casewit, K. S. Colwell, and A. K. Rappé, “Application of a universal force field to main group compounds,” Journal of the American Chemical Society, vol. 114, no. 25, pp. 10046–10053, 1992. View at Google Scholar · View at Scopus
  74. J. N. Murrell and K. J. Laidler, “Symmetries of activated complexes,” Transactions of the Faraday Society, vol. 64, pp. 371–377, 1968. View at Publisher · View at Google Scholar · View at Scopus
  75. K. Muller, “Reaction paths on multidimensional energy hypersurfaces,” Angewandte Chemie, vol. 19, no. 1, pp. 1–13, 1980. View at Publisher · View at Google Scholar
  76. E. Cancès, B. Mennucci, and J. Tomasi, “A new integral equation formalism for the polarizable continuum model: theoretical background and applications to Isotropic and anisotropic dielectrics,” Journal of Chemical Physics, vol. 107, no. 8, pp. 3032–3041, 1997. View at Google Scholar · View at Scopus
  77. B. Mennucci and J. Tomasi, “Continuum solvation models: a new approach to the problem of solute's charge distribution and cavity boundaries,” Journal of Chemical Physics, vol. 106, no. 12, pp. 5151–5158, 1997. View at Google Scholar · View at Scopus
  78. B. Mennucci, E. Cancès, and J. Tomasi, “Evaluation of solvent effects in isotropic and anisotropic dielectrics and in ionic solutions with a unified integral equation method: theoretical bases, computational implementation, and numerical applications,” Journal of Physical Chemistry B, vol. 101, no. 49, pp. 10506–10517, 1997. View at Google Scholar · View at Scopus
  79. J. Tomasi, B. Mennucci, and E. Cancès, “The IEF version of the PCM solvation method: an overview of a new method addressed to study molecular solutes at the QM ab initio level,” Journal of Molecular Structure, vol. 464, no. 1–3, pp. 211–226, 1999. View at Publisher · View at Google Scholar · View at Scopus
  80. J. McAinsh, W. T. Simpson, and B. F. Holmes, “Bioavailability of atenolol formulations,” Biopharmaceutics and Drug Disposition, vol. 1, no. 6, pp. 323–332, 1980. View at Google Scholar · View at Scopus
  81. H. Vergin and V. Nitsche, “Oral bioavailability of atenolol,” Journal of International Medical Research, vol. 17, no. 5, pp. 417–425, 1989. View at Google Scholar · View at Scopus
  82. http://en.wikipedia.org/wiki/atenolol.
  83. R. Hipple and M. Nahahta, “Atenolol oral suspension,” in Pediatric Drug Formulations, 4th edition, 2000. View at Google Scholar
  84. http://www.assistpainrelief.com/dyn/304/Paracetamol.html.
  85. http://www.chemicalbook.com/ChemicalProductProperty_EN_CB6141828.htm.
  86. http://www.chemicalall.com/chemicals-name-a/acetanilide.html.
  87. T. Katagi, “AM1 study of acid-catalyzed hydrolysis of maleamic (4-amino-4-oxo-2-butenoic) acids,” Journal of Computational Chemistry, vol. 11, no. 9, pp. 1094–1100, 1990. View at Publisher · View at Google Scholar
  88. R. Kluger and J. Chin, “Carboxylic acid participation in amide hydrolysis. Evidence that separation of a nonbonded complex can be rate determining,” Journal of the American Chemical Society, vol. 104, no. 10, pp. 2891–2897, 1982. View at Google Scholar · View at Scopus
  89. R. Karaman, “Effects of substitution on the effective molarity (EM) for five membered ring-closure reactions—a computational approach,” Journal of Molecular Structure, vol. 939, no. 1–3, pp. 69–74, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. R. Karaman, “The effective molarity (EM) puzzle in intramolecular ring-closing reactions,” Journal of Molecular Structure, vol. 940, no. 1–3, pp. 70–75, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. R. Karaman, “The effective molarity (EM)-A computational approach,” Bioorganic Chemistry, vol. 38, no. 4, pp. 165–172, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. A. J. Kirby, “Effective molarities for intramolecular reactions,” Journal of Physical Organic Chemistry, vol. 18, pp. 101–278, 2005. View at Google Scholar