Identification, Characterization and Evaluation of Crystal Forms of Quinine Sulphate

Maninder  Karan; Renu  Chadha; Kunal  Chadha; Poonam  Arora

doi:10.4236/pp.2012.32020

Journals by Subject

Journals by Title

PP Vol.3 No.2 , April 2012

Identification, Characterization and Evaluation of Crystal Forms of Quinine Sulphate

Maninder Karan^*, Renu Chadha, Kunal Chadha, Poonam Arora

Abstract: Crystal engineering concept has been utilized to modify the physico-chemical parameters of a naturally occurring alkaloid, quinine sulphate, by exploring its H-bond interactions to generate different forms. Quinine sulphate is found to exist in four different crystal forms. The Forms I and II depict endo/exo events suggesting conversion of metastable low melting forms to higher melting and stable form indicated by sharp melting endotherms. The low melting form IL is found to be monotropically related to high melting Form IH while low melting Form IIL is enantiotropically related to high melting Form IIH. The Form III and IV showed broad endotherms accompanied by mass loss in TGA prior to melting indicating the existence of solvatomorphism. The solvent molecules are tightly bound in the crystal lattice of the drug molecules which is shown by high values of the binding energies of the solvents in these two forms. The enthalpy of solution was found to be endothermic for all the forms which followed the order: Form O > Form II > Form III > Form I > Form IV and is further related to the lattice energy suggesting Form II to be least crystalline. The solubility for Form II was found to be highest with maximum release rate in dissolution studies. The effectiveness of new polymorphic forms was confirmed by performing in vivo antimalarial activity against P. berghei infection. The studies have shown an increase in antimalarial activity of Form IV concluding a successful development of new polymorphic form.

Keywords: Quinine Sulphate; Enthalpy; Polymorphs; Solvates; Crystals

Cite this paper: M. Karan, R. Chadha, K. Chadha and P. Arora, "Identification, Characterization and Evaluation of Crystal Forms of Quinine Sulphate," Pharmacology & Pharmacy, Vol. 3 No. 2, 2012, pp. 129-138. doi: 10.4236/pp.2012.32020.

References

[1] J. D. Newman and G. M. Cragg, “Natural Products as Sources of New Drugs over the Last 25 Years,” Journal of Natural Products, Vol. 70, No. 3, 2007, pp. 461-477. doi:10.1021/np068054v

[2] J. Kelland, S. Y. Sharp and P. M. Rogers, “DT-Diaphorase Expression and Tumor Cell Sensitivity to 17- Allylamino, 17-Demethoxygeldanamycin, an Inhibitor of Heat Shock Protein 90,” Journal of National Cancer Institute, Vol. 91, No. 22, 1999, pp. 1940-1949. doi:10.1093/jnci/91.22.1940

[3] C. A. Lipinski, F. Lombardo, B. W. Dominy and P. J. Feeney, “Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings,” Advanced Drug Delivery Review, Vol. 46, No. 1-3, 2001, pp. 3-26. doi:10.1016/S0169-409X(00)00129-0

[4] M. R. Roberts and M. Wink, “Alkaloids,” In: T. Acamovic, C. S. Stewart and T. W. Pennycott, Eds., Biochemistry, Ecology and Medical Applications, Plenum Press, New York, 1998.

[5] C. W. Evans, “Trease and Evans Pharmacognosy,” 16th Edition, W. B. Saunders and Company Ltd., London, 2002, pp. 333-393.

[6] A. R. Battersby, “Research on Alkaloids in Retrospect and in Prospect,” Tetrahedron, Vol. 14, No. 1-2, 1961, pp. 1-7. doi:10.1016/0040-4020(61)80082-3

[7] N. Khan and S. Aripov, “The Technological Classification of Alkaloids and Methods of Obtaining Them from Plant,” Chemistry of Natural Compounds, Vol. 13, No. 6, 1984, pp. 624-634.

[8] D. J. Newman and G. M. Cragg, “Natural Products as Sources of New Drugs over the Last 25 Years,” Journal of Natural Products, Vol. 70, No. 3, 2007, pp. 461-477. doi:10.1021/np068054v

[9] L. M. Harwood and C. J. Moody, “Experimental Organic Chemistry: Principles and Practice,” 4th Edition, Blackwell Scientific, Oxford, 2003, pp. 118-122.

[10] W. P. Jones and A. D. Kinghorn, “Extraction of Plant Secondary Metabolites,” Natural Products Isolation, Vol. 20, No. 2, 2005, pp. 323-351.

[11] G. V. Burchianti, C. Marcello, F. De Andrade and R. D. Albuquerque, “Process for the Extraction and Purification of Alkaloids,” U.S. Patent Number 5684155, 1996.

[12] R. J. Parry, “Biosynthesis of the Cinchona Alkaloids: Middle Stages of the Pathway,” Chemical Communications, Vol. 30, 1971, pp. 123-130.

[13] D. J. Berrisford, C. Bolm and K. B. Sharpless, “Ligand-Accelerated Catalysis,” Angewandte Chemie International Edition, Vol. 34, No. 10, 1995, pp. 1059-1070. doi:10.1002/anie.199510591

[14] J. K. Haleblian, “Characterization of Habits and Crystalline Modification of Solids and Their Pharmaceutical Applications,” Journal of Pharmaceutical Sciences, Vol. 64, No. 8, 1975, pp. 1269-1288. doi:10.1002/jps.2600640805

[15] J. Bernstein, “Polymorphism in Molecular Crystals,” Oxford University Press, Oxford, 2002.

[16] K. R. Nielsen, T. Sun, K. Lorimer, K. W. Meyer and S. Watson, “Qunine Sulphate Polymorphs, Process of Preparing, Compositions and Uses Thereof,” US AA61K31439F1, 2009.

[17] A. A. Andradea, F. P. Varottia, I. O. Freitasa, M. V. N. Souzab, T. R. A. Vasconcelosb, N. Boechatb, A. U. Krettlia, “Enhanced Activity of Mefloquine and Artesunic Acid against Plasmodium falciparum in vitro and P. berghei in Mice by Combination with Ciprofloxacin,” European Journal of Pharmacology, Vol. 558, No. 1-3, 2007, pp. 194-198. doi:10.1016/j.ejphar.2006.11.061

[18] D. Giron, “Thermal Analysis and Calorimetric Methods in the Characterization of Polymorphs and Solvates,” Thermochim Acta, Vol. 248, 1995, pp. 1-59. doi:10.1016/0040-6031(94)01953-E

[19] A. Othman, J. S. O. Evans, I. R. Evans and R. K. Harris, “Structural Study of Polymorphs and Solvates of Finasteride,” Journal of Pharmaceutical Sciences, Vol. 96, No. 5, 2007, pp. 1380-1397. doi:10.1002/jps.20940

[20] M. R. Caira, G. Bettinetti, M. Sorrenti and L. Catenacci, “Relationships between Structural and Thermal Properties of Anhydrous and Solvated Crystalline Forms of Brodimoprim,” Journal of Pharmaceutical Sciences, Vol. 96, No. 5, 2007, pp. 996-1007. doi:10.1002/jps.20934

[21] R. Chadha, P. Arora, A. Saini and D. V. S. Jain, “Solvated Crystalline Forms of Nevirapine: Thermoanalytical and Spectroscopic Studies,” AAPS Pharm Sci Tech, Vol. 11, No. 3, 2010, pp. 1328-1339. doi:10.1208/s12249-010-9511-z