2
292
RESEARCH ARTICLE – Pharmaceutics, Drug Delivery and Pharmaceutical Technology
CONCLUSIONS
14. Pop M, Sieger P, Cains PW. 2009. Tiotropium fumarate:
An interesting pharmaceutical co-crystal. J Pharm Sci 98:1820–
On the basis of the solution 13C NMR spectra, the dipolar-
dephased NMR experiments and the GIPAW calculations we
1834.
15. Diulgheroff N, Scarpitta F, Pontiroli A, Kovacsne-Mezel A, Aron-
13
have assigned C CP/MAS NMR spectra of TIOA and TIOH. hime J, Jegorov A. 2007. Novel forms of tiotropium bromide and pro-
We have demonstrated that looking at the differences in the cesses for preparation thereof. Patent WO2007/075858 A2.
spectra of those polymorphs it is easy to distinguish them us- 16. Allen FH. 2002. The Cambridge Structural Database: A quar-
ter of a million crystal structures and rising. Acta Cryst B58:380–
ing ssNMR spectroscopy. The NMR chemical shifts calculated
388.
on the basis of previously published crystal structures of TIOA
and TIOH did not agree with the experimental values. As the
GIPAW calculations are very sensitive to the atom positions,
those divergent results indicated that the analyzed CSD struc-
tures contain some major errors. Those errors were identified
and corrected by us using the BFGS method of geometry opti-
17. Sieger P, Werthmann U. 2003. Crystalline anticholinergic processes
for preparing it and its use for preparing a pharmaceutical composition.
Patent US6608055 B2.
18. Banholzer R, Sieger P, Kulinna Ch, Trunk M, Graulich M, Specht P,
Meissner H, Mathes A. 2004. Crystalline tiotropium bromide monohy-
drate, processes for the preparation thereof, and pharmaceutical com-
mization employed within the CASTEP code. The accuracy of positions. Patent US6777423 B2.
the optimized structures was confirmed using the ssNMR and 19. Head JD, Zerner MC. 1985. A Broyden-Fletcher-Goldfarb-Shanno
PXRD methods. Therefore, we have shown that this approach optimization procedure for molecular geometries. Chem Phys Lett
1
2
22:264–270.
can be used not only to perform the structural analysis of a drug
compound and to easily differentiate its polymorphs, but also
to verify and improve its already published crystal structure.
¨
0. Nyberg K, Ostman B, Wallerberg G. 1970. Investigations of
dithienylglycolic esters. I. Preparation of methyl dithienylglycolates.
Magnetically nonequivalent protons in dithienylglycolates. Acta Chim
Scand 24:1590–1596.
2
1. Busolli J, Diulgheroff N, Pontiroli A, Scarpitta F, Volonte R. 2008.
REFERENCES
Scopine salts and their use in processes for the preparation of n-
1. de Boer AH, Hagedoorn P. 2015. The role of disposable inhalers in demethyl-tiotropium and tiotropium bromide. Patent WO2008008376
pulmonary drug delivery. Expert Opin Drug Deliv 12:143–157.
A8.
2. Rau JL. 2005. The inhalation of drugs: Advantages and problems. 22. Banholzer R, Bauer R, Reichl R. 1997. Esters of thienyl carboxylic
Respir Care 50:367–382.
acids and amino alcohols and their quaternization products. Patent
3. Ikegami K, Kawashima Y, Takeuchi H, Yamamoto H, Isshiki N, US5610163.
Momose D, Ouchi K. 2002. Improved inhalation behavior of steroid 23. Pines A, Gibby MG, Waugh JS. 1973. Proton-enhanced NMR of
KSR-592 in vitro with Jethaler by polymorphic transformation to dilute spins in solids. J Chem Phys 59:569–590.
needle-like crystals (beta-form). Pharm Res 19:1439–1445.
24. ACD/SpecMenager, version 10.08, Advanced Chemistry Develop-
4. Bauer J, Spanton S, Henry R, Quick J, Dziki W, Porter W, Morris J.
ment, Inc., 2007, http://www.acdlabs.com/.
2
001. Ritonavir: An extraordinary example of conformational polymor- 25. Segall MD, Lindan PJD, Probert MJ, Pickard CJ, Hasnip PJ, Clark
SJ, Payne MC. 2002. First-principles simulation: Ideas, illustrations
. Palmer DS, Llin a` s A, Morao I, Day GM, Goodman JM, Glen RC, and the CASTEP code. J Phys Condens Matter 14:2717–2744.
Mitchell JB. 2008. Predicting intrinsic aqueous solubility by a thermo- 26. Yates JR, Pickard CJ, Mauri F. 2007. Calculation of NMR chemical
dynamic cycle. Mol Pharm 5:266–279.
shifts for extended systems using ultrasoft pseudopotentials. Phys Rev
. Pindelska E, Dobrzycki L, Wo z´ niak K, Kolodziejski W. 2011. Poly- B 76:024401 .
morphism of crystalline 4-amino-2-nitroacetanilide. Cryst Growth Des 27. Materials Studio v 6.1 Copyright Accelrys Software Inc. 2013,
phism. Pharm Res 18:859–866.
5
6
1
7
1
1:2074–2083.
http://accelrys.com/products/materials-studio/.
. Zieli n´ ska-Pisklak M, Pisklak DM, Wawer I. 2012. Application of 28. Tkatchenko A, Scheffler M. 2009. Accurate molecular van der Waals
3C CPMAS NMR for qualitative and quantitative characterization of interactions from ground-state electron density and free-atom refer-
carvedilol and commercial formulations. J Pharm Sci 101:1763–1772.
ence data. Phys Rev Lett 102073005.
. Pindelska E, Szeleszczuk L, Pisklak DM, Mazurek A, Kolodziejski 29. Pickard CJ, Mauri F. 2001. All-electron magnetic response with
8
W. 2015. Solid-state NMR as an effective method of polymorphic anal-
pseudopotentials: NMR chemical shifts. Phys Rev B 63:2451011–
ysis: Solid dosage forms of clopidogrel hydrogensulfate. J Pharm Sci
2451013.
104:106–113.
30. Pearson M. 2004. Chronic obstructive pulmonary disease: National
9. Barnes PJ. 2000. The pharmacological properties of tiotropium. clinical guideline on management of chronic obstructive pulmonary
Chest 117:63S–66S.
disease in adults in primary and secondary care. Thorax 59:1–232.
10. Casaburi R, Mahler DA, Jones PW, Wanner A, San PG, ZuWallack
31. Guilbaud JB, Clark BC, Meehan E, Hughes L, Saiani A, Khimyak
RL, Menjoge SS, Serby CW, Witek Jr. T. 2002. A long-term evalua- YZ. 2010. Effect of encapsulating a pseudo-decapeptide containing argi-
tion of once-daily inhaled tiotropium in chronic obstructive pulmonary nine on PLGA: A solid-state NMR study. J Pharm Sci 99:2681–2696.
disease. Eur Respir J 19:217–224.
32. Pindelska E, Sokal A, Szeleszczuk L, Pisklak DM, Kolodziejski W.
1. Friedman M, Menjoge SS, Anton SF, Kesten S. 2004. Healthcare 2014. Solid-state NMR studies of theophylline co-crystals with dicar-
1
costs with tiotropium plus usual care versus usual care alone following
boxylic acids. J Pharm Biomed Anal 100:322–328.
1
year of treatment in patients with chronic obstructive pulmonary 33. Mazur L, Jarz e˛ bska KN, Kami n´ ski R, Wo z´ niak K, Pindelska E,
disorder (COPD). Pharmacoeconomics 22:741–749.
Zieli n´ ska-Pisklak M. 2014. Substituent and solvent effects on in-
12. Rice KL, Kunisaki KM, Niewoehner DE. 2007. Role of tiotropium in termolecular interactions in crystals of N-acylhydrazone derivatives:
the treatment of COPD. Int J Chron Obstruct Pulmon Dis 22:95–105.
Single-crystal X-ray, solid-state NMR, and computational studies.
Cryst Growth Des 14:2263–2281.
13. D’Souza AO, Smith MJ, Miller LA, Kavookjian J. 2006. An ap-
praisal of pharmacoeconomic evidence of maintenance therapy for 34. Bak B, Christensen D, Hansen-Nygaard L, Rastrup-Andersen J.
COPD. Chest 129:1693–1708.
1961. The structure of thiophene. J Mol Spectr 7:58–63.
Pindelska et al., JOURNAL OF PHARMACEUTICAL SCIENCES 104:2285–2292, 2015
DOI 10.1002/jps.24490