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Study of the molecular mobility of (±)-methocarbamol in the amorphous solid state

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Abstract

The experimental techniques of differential scanning calorimetry (DSC) and thermally stimulated depolarization currents (TSDC) were used to study the thermal behavior of the pharmaceutical drug (±)-methocarbamol and its slow molecular mobility (in the 10−3–10−2 Hz range) in the amorphous solid state. The possibility of polymorphism was considered based on the DSC results. The glass forming ability and the glass stability were investigated by DSC, and the general kinetic features of the main relaxation, including the fragility or steepness index, were studied by both experimental techniques. The secondary relaxations detected by TSDC revealed fast and slow (Johari-Goldstein) modes. These secondary relaxations of different nature were assigned based on physical aging studies.

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References

  1. B.C. Hancock, G. Zografi, Characteristics and significance of the amorphous state in pharmaceutical systems, J. Pharm. Sci. 86, 1 (1997)

    Article  Google Scholar 

  2. L. Yu, Amorphous pharmaceutical solids: preparation, characterization and stabilization, Adv. Drug. Delivery Rev. 48, 27 (2001)

    Article  Google Scholar 

  3. A.M. Kaushal, P. Gupta, A.K. Bansal, Amorphous drug delivery systems: molecular aspects, design, and performance, Crit. Rev. Ther. Drug. Carrier Syst. 21, 133 (2004)

    Article  Google Scholar 

  4. P. Karmwar, K. Graeser, K.C. Gordon, C.J. Strachan, T. Rades, Investigation of properties and recrystallisation behaviour of amorphous indomethacin samples prepared by different methods, Int. J. Pharm. 417, 94 (2011)

    Article  Google Scholar 

  5. A.W. Lim, K. Löbmann, H. Grohganz, T. Rades, N. Chieng, Investigation of physical properties and stability of indomethacin-cimetidine and naproxen-cimetidine co-amorphous systems prepared by quench cooling, coprecipitation and ball milling, J. Pharm. Pharmacol. 68, 36 (2016)

    Article  Google Scholar 

  6. S. Bhattacharya, R. Suryanarayanan, Local mobility in amorphous pharmaceuticals-characterization and implications on stability, J. Pharm. Sci. 98, 2935 (2009)

    Article  Google Scholar 

  7. K. Kothari, V. Ragoonanan, R. Suryanarayanan, Influence of molecular mobility on the physical stability of amorphous pharmaceuticals in the supercooled and glassy states, Mol. Pharm. 11, 3048 (2014)

    Article  Google Scholar 

  8. Y. Aso, S. Yoshioka, S. Kojima, Explanation of the crystallization rate of amorphous nifedipine and phenobarbital from their molecular mobility as measured by 13C nuclear magnetic resonance relaxation time and the relaxation time obtained from the heating rate dependence of the glass transition temperature, J. Pharm. Sci. 90, 798 (2001)

    Article  Google Scholar 

  9. S.P. Bhardwaj, K.K. Arora, E. Kwong, A. Templeton, S.D. Clas, R. Suryanarayanan, Correlation between molecular mobility and physical stability of amorphous itraconazole, Mol. Pharm. 10, 694 (2013)

    Article  Google Scholar 

  10. M. Mehta, V. Ragoonanan, G.B. McKenna, R. Suryanarayanan, Correlation between Molecular Mobility and Physical Stability in Pharmaceutical Glasses, Mol. Pharm. 13, 1267 (2016)

    Article  Google Scholar 

  11. M. Yoshioka, B.C. Hancock, G. Zografi, Crystallization of Indomethacin from the Amorphous State Below and Above Its Glass-Transition Temperature, J. Pharm. Sci. 83, 1700 (1994)

    Article  Google Scholar 

  12. K. Grzybowska, M. Paluch, A. Grzybowski, Z. Wojnarowska, L. Hawelek, K. Kolodziejczyk, K.L. Ngai, Molecular Dynamics and Physical Stability of Amorphous Anti-Inflammatory Drug: Celecoxib, J. Phys. Chem. B. 114, 12792 (2010)

    Article  Google Scholar 

  13. G. Van den Mooter, The use of amorphous solid dispersions: A formulation strategy to overcome poor solubility and dissolution rate, Drug. Discovery Today: Technologies 9, e79 (2012)

    Article  Google Scholar 

  14. T. Vasconcelos, S. Marques, J. das Neves, B. Sarmento, Amorphous solid dispersions: Rational selection of a manufacturing process, Adv. Drug. Delivery Rev. 100, 85 (2016)

    Article  Google Scholar 

  15. M.K. Riekes, A. Engelen, B. Appeltans, P. Rombaut, H.K. Stulzer, G. Van den Mooter, New Perspectives for Fixed Dose Combinations of Poorly Water-Soluble Compounds: a Case Study with Ezetimibe and Lovastatin, Pharm Res 33, 1259 (2016)

    Article  Google Scholar 

  16. S.J. Dengale, H. Grohganz, T. Rades, K. Löbmann, Recent advances in co-amorphous drug formulations, Adv. Drug. Delivery Rev. 100, 116 (2016)

    Article  Google Scholar 

  17. S. Alessi-Severini, F. Jamali, R.T. Coutts, F.M. Pasutto, Methocarbamol (Academic Press, San Diego, 1994), pp. 371–399

  18. A.A. Bredikhin, Z.A. Bredikhina, D.V. Zakharychev, A.V. Pashagin, Chiral drugs related to guaifenesin: synthesis and phase properties of methocarbamol and mephenoxalone, Tetrahedron: Asymmetry 18, 1239 (2007)

    Article  Google Scholar 

  19. J.J. Moura Ramos, R. Taveira-Marques, H.P. Diogo, Estimation of the fragility index of indomethacin by DSC using the heating and cooling rate dependency of the glass transition, J. Pharm. Sci. 93, 1503 (2004)

    Article  Google Scholar 

  20. H.P. Diogo, M.T. Viciosa, J.J. Moura Ramos, Thermally Stimulated Currents: principles, methods for data processing and significance of the information provided, Supplementary Data to Thermochimica Acta 623, 29 (2016)

    Article  Google Scholar 

  21. G. Teyssedre, C. Lacabanne, Some considerations about the analysis of thermostimulated depolarization peaks, J. Phys. D: Appl. Phys. 28, 1478 (1995)

    Article  ADS  Google Scholar 

  22. J. van Turnhout, Thermally Stimulated Discharge of Polymer Electrets (Elsevier Sci. Pub. Co., Amsterdam, 1975)

  23. R. Chen, Y. Kirsh, Analysis of Thermally Stimulated Processes (Pergamon Press, Oxford, 1981)

  24. J. van Turnhout, Thermally stimulated discharge of electrets, in G.M. Sessler, editor. Electrets (Springer, Berlin, Heidelberg, 1987), pp. 81–lpg215

  25. V.M. Gun’ko, V.I. Zarko, E.V. Goncharuk, L.S. Andriyko, V.V. Turov, Y.M. Nychiporuk, R. Leboda, Skubiszewska-J. Zieba, A.L. Gabchak, V.D. Osovskii, Y.G. Ptushinskii, G.R. Yurchenko, O.A. Mishchuk, P.P. Gorbik, P. Pissis, J.P. Blitz, TSDC spectroscopy of relaxational and interfacial phenomena, Adv. Colloid. Interface Sci. 131, 1 (2007)

    Article  Google Scholar 

  26. B.B. Sauer, Thermally Stimulated Currents: recent developments in characterisation and analysis of polymers, in Applications to Polymers and Plastics, edited by S.Z.D. Cheng (Elsevier, Amsterdam, 2002), pp. 653–711

  27. A. Vassilikou-Dova, I.M. Kalogeras, Dielectric analysis (DEA), in Thermal Analysis of Polymers: Fundamentals and Applications, edited by J.D. Menczel, R.B. Prime, 1st edn (John Wiley, Hoboken, New Jersey, 2009), pp. 497–613

  28. N. Boutonnet-Fagegaltier, A. Lamure, J. Menegotto, C. Lacabanne, A. Caron, H. Duplaa, M. Bauer, The use of thermally stimulated current spectroscopy in the pharmaceutical sciences, in Thermal Analysis of Pharmaceuticals, edited by D.Q.M. Craig, M. Reading (CRC Press, Boca Raton, 2007), pp. 359–382

  29. S. Baker, M.D. Antonijevic, Thermal analysis - dielectric techniques, in Solid State Characterization of Pharmaceutics, edited by R.A. Storey, I. Ymén (Wiley, Chichester, UK, 2011), pp. 187–206

  30. M.K. Saini, S.S.N. Murthy, Study of glass transition phenomena in the supercooled liquid phase of methocarbamol, acetaminophen and mephenesin, Thermochim Acta 575, 195 (2014)

    Article  Google Scholar 

  31. K.C. Mercado, G.A. Rodríguez, D.R. Delgado, F. Martínez, A. Romdhani, Solution thermodynamics of methocarbamol in some ethanol + water mixtures, Quím. Nova 35, 1967 (2012)

    Article  Google Scholar 

  32. A.A. Bredikhin, A.T. Gubaidullin, Z.A. Bredikhina, D.B. Krivolapov, A.V. Pashagin, I.A. Litvinov, Absolute configuration and crystal packing for three chiral drugs prone to spontaneous resolution: Guaifenesin, methocarbamol and mephenesin, J. Molec. Struct. 920, 377 (2009)

    Article  ADS  Google Scholar 

  33. J.J. Moura Ramos, H.P. Diogo, M.H. Godinho, C. Cruz, K. Merkel, Anomalous thermal behavior of salicylsalicylic acid and evidence for a monotropic transition to a nematic phase, J. Phys. Chem. B 108, 7955 (2004)

    Article  Google Scholar 

  34. R. Svoboda, J. Málek Description of enthalpy relaxation dynamics in terms of TNM model, J. Non-Cryst Solids 378, 186 (2013)

    Article  ADS  Google Scholar 

  35. R. Svoboda, How to determine activation energy of glass transition, J. Therm. Anal. Calorim. 118, 1721 (2014)

    Article  Google Scholar 

  36. C.T. Moynihan, A.J. Easteal, J. Wilder, J. Tucker, Dependence of the glass transition temperature on heating and cooling rate, J. Phys. Chem. 78, 2673 (1974)

    Article  Google Scholar 

  37. C.A. Angell, Relaxation in liquids, polymers and plastic crystals – strong/fragile patterns and problems, J. Non-Cryst. Solids 131–133, 13 (1991)

    Article  Google Scholar 

  38. R. Böhmer, C.A. Angell, Local and global relaxations in glass-forming materials, in Disorder Effects on Relaxational Processes, edited by R. Richert, A. Blumen (Springer-Verlag, Berlin, 1994), pp. 11–54

  39. L.M. Wang, C.A. Angell, Response to Comment on Direct determination of the fragility indices of glassforming liquids by differential scanning calorimetry: Kinetic versus thermodynamic fragilities, J. Chem. Phys. 118, 10351 (2003)

    Article  Google Scholar 

  40. L.M. Wang, C.A. Angell, R. Richert, Fragility and thermodynamics in nonpolymeric glass-forming liquids, J. Chem. Phys. 125, 074505 (2006)

    Article  ADS  Google Scholar 

  41. X. Xia, P.G. Wolynes, Fragilities of liquids predicted from the random first order transition theory of glasses, Proc. Natl. Acad. Sci. USA 97, 2990 (2000)

    Article  ADS  Google Scholar 

  42. N.T. Correia, C. Alvarez, J.J. Moura Ramos, Fragility in side-chain liquid crystalline polymers: the TSDC contribution, Polymer 41, 8625 (2000)

    Article  Google Scholar 

  43. N.T. Correia, C. Alvarez, J.J. Moura Ramos, M. Descamps, Molecular motions in molecular glasses as studied by thermally stimulated depolarisation currents (TSDC), Chem. Phys. 252, 151 (2000)

    Article  ADS  Google Scholar 

  44. J.J. Moura Ramos, N.T. Correia, The Deborah number, relaxation phenomena and thermally stimulated currents, Phys. Chem. Chem. Phys. 3, 5575 (2001)

    Article  Google Scholar 

  45. H.W. Starkweather, Simple and complex relaxations, Macromolecules 14, 1277 (1981)

    Article  ADS  Google Scholar 

  46. H.W. Starkweather, Noncooperative relaxations, Macromolecules 21, 1798 (1988)

    Article  ADS  Google Scholar 

  47. H.W. Starkweather, Aspects of simple, non-cooperative relaxations, Polymer 32, 2443 (1991)

    Article  Google Scholar 

  48. N.T. Correia, J.J. Moura Ramos, On the cooperativity of the β-relaxation: A discussion based on dielectric relaxation and thermally stimulated depolarisation currents data, Phys. Chem. Chem. Phys. 2, 5712 (2000)

    Article  Google Scholar 

  49. J.J. Moura Ramos, H.P. Diogo, S.S. Pinto Local motions in L-iditol glass: identifying different types of secondary relaxations, Thermochim. Acta 467, 107 (2008)

    Article  Google Scholar 

  50. S.S. Pinto, J.J. Moura Ramos, H.P. Diogo, The slow molecular mobility in poly(vinyl acetate) revisited: new contributions from Thermally Stimulated Currents, Eur. Polym. J. 45, 2644 (2009)

    Article  Google Scholar 

  51. E. Mora, H.P. Diogo, J.J. Moura Ramos, The slow molecular dynamics in amorphous probucol, Thermochim. Acta 595, 83 (2014)

    Article  Google Scholar 

  52. H.P. Diogo, J.J. Moura Ramos, Contribution of the technique of thermostimulated currents for the elucidation of the nature of the Johari-Goldstein and other secondary relaxations in the vitreous state, IEEE Trans. Dielect. Elect. Insul. 21, 2301 (2014)

    Article  Google Scholar 

  53. M. Paluch, C.M. Roland, S. Pawlus, J. Ziolo, K.L. Ngai, Does the Arrhenius temperature dependence of the Johari-Goldstein relaxation persist above T(g)? Phys. Rev. Lett. 91, 115701 (2003)

    Article  ADS  Google Scholar 

  54. K.L. Ngai, Relaxation and diffusion in complex systems (Springer, New York, 2011)

  55. K.L. Ngai, An extended coupling model description of the evolution of dynamics with time in supercooled liquids and ionic conductors, J. Phys.: Condens. Matter 15, S1107 (2003)

    ADS  Google Scholar 

  56. S. Capaccioli, K.L. Ngai, Relation between the alpha-relaxation and Johari-Goldstein beta-relaxation of a component in binary miscible mixtures of glass-formers, J. Phys. Chem. B 109, 9727 (2005)

    Article  Google Scholar 

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Authors and Affiliations

  1. CQFM – Centro de Química-Física Molecular and IN – Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, 1049-001, Lisboa, Portugal

    Joaquim J. Moura Ramos

  2. CQE – Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, 1049-001, Lisboa, Portugal

    Hermínio P. Diogo

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  1. Joaquim J. Moura Ramos
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Correspondence to Hermínio P. Diogo.

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Moura Ramos, J.J., Diogo, H.P. Study of the molecular mobility of (±)-methocarbamol in the amorphous solid state. Eur. Phys. J. Spec. Top. 226, 889–904 (2017). https://doi.org/10.1140/epjst/e2016-60233-y

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