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K. Adrjanowicz , Z. Wojnarowska, P. Wlodarczyk, K. Grzybowska, K. Kaminski, M. Paluch

Molecular dynamics in pharmaceutically important hydrochloride salts studied by Dielectric Spectroscopy. K. Adrjanowicz , Z. Wojnarowska, P. Wlodarczyk, K. Grzybowska, K. Kaminski, M. Paluch Institute of Physics, University of Silelesia , Katowice, Poland.

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K. Adrjanowicz , Z. Wojnarowska, P. Wlodarczyk, K. Grzybowska, K. Kaminski, M. Paluch

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  1. Molecular dynamics in pharmaceuticallyimportant hydrochloride saltsstudied by DielectricSpectroscopy K. Adrjanowicz, Z. Wojnarowska, P. Wlodarczyk, K. Grzybowska, K. Kaminski, M. Paluch Institute of Physics, University of Silelesia, Katowice, Poland

  2. Tramadol HCL solubility ->300 mg/ml bioavailability -> 68–72% Increases with repeated dosing. Tramadol Tramadol hydrochloride Examinedcompounds Crystalline VH is soluble in water (i.e. 82 mg/mL at pH 2.32, 0.44 mg/mL at pH=7.32). More than 90% of the oral administer dose is absorbed from the gastrointestinal track, where pH is roughly 2-4. However only 10-20% out of these 90% absorbed from the digestive track get into circulatory system (pH blood about 7.34 – 7.43). Verapamil hydrochloride

  3. Relaxation Dynamics In Tramadol The glass transition temperature Tg was defined as a temperature at which =100s.

  4. Tramadol „Excesswing” in Tramadol The Coupling Model prediction

  5. Tramadol Temperature VFT law: Relaxation map of Tramadol Fragility The Arrhenius equation:

  6. Relaxation Dynamics In Supercooled TH and VH

  7. Theprediction of thenature of b-relaxationin TH The Coupling Model prediction bKWW-M=0.65 The well-separated b-process in TH is the Johari-Goldstein process

  8. Aging at T=313K „Excesswing” in VH The excess wing in VH is the JG process

  9. Temperature VFT law: TH - Relaxation map Fragility The Arrhenius equation:

  10. Relaxation map in VH

  11. Molecularmobility and stabilityagainstcrystallization We link an opposite trend to crystallization of both pharmaceuticals with different local molecular mobility. The ability of amorphous pharmaceuticals to crystallization might be correlate to the asymmetric distribution of structural relaxation time, described by the bKWW parameter - Shamblin S.L., Hancock B.C., Dupuis Y., Pikal M.J., J.Pharm.Sci., 89, 417-427 (1999)

  12. No significant differences between amorphous and crystalline tramadol hydrochloride in intrinsic dissolution test rate were observed Dissolution profile of amorphous Tramadol hydrochloride It was affirmed that amorphous tramadol hydrochloride compacted better than crystalline. Amorphous tramadol hydrochloride requires about 30% less pressure force than the drug in crystalline state to obtain tablets with similar physical parameters Cooperation: Department of Pharmaceutical Technology, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland W. Sawicki , P. Lepek , R. Lunio, J. Mazgalski

  13. Solubility and intrinsic dissolution rate obtained for amorphous verapamil hydrochloride are much better than that derived for crystalline API. It was found the statistically significant difference between IDR calculated for crystalline and amorphous form. The obtained results amounted to 7,61 and 8,89 mg*min-1*cm-1 for crystalline and amorphous form respectively. Solubility and dissolutionrate of amorphous VH Cooperation: Department of Pharmaceutical Technology, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland W. Sawicki , P. Lepek , R. Lunio, J. Mazgalski

  14. 1. We showed that dielectric spectroscopy can be satisfactorily used to follow dynamics of hydrochloride salts, despite theirs ionic character. Up to know BDS was used to measure only pure API’s, while in the case of their salts this experimental technique failed because of great contribution of the dc conductivity to the loss spectra.Presentation of the dielectric data in modulus representation enabled us to get valuable information about dynamics of the investigated system Summary 2. Chemical transition of drug from monohydrate into hydrochloride salt results in significant increase of its glass transition. As a consequence it is possible to prepare its oral dosage form completely amorphous in the room temperature and even human body temperature. 3. Both analyzed by us compounds differ in separation of JG relaxation. Thus, we relate completly opposite trend to crystallization of both pharmaceuticals with different local molecular mobility. 4. Amorphous drugs can be alternative even for the well solved pharmaceuticals

  15. The authors are deeply thankful for the financial support of their research within the framework of the project entitled /From Study of Molecular Dynamics in Amorphous Medicines at Ambient  and Elevated Pressure to Novel Applications in Pharmacy/, which is operated within the Foundation for Polish Science Team Programme co-financed by the EU European Regional Development Fund. Acknowledgments

  16. Thank you for yourattention

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