International E-publication: Publish Projects, Dissertation, Theses, Books, Souvenir, Conference Proceeding with ISBN.  International E-Bulletin: Information/News regarding: Academics and Research

Preparation, Characterization of Hydrates and Anhydrous Forms of Anti migraine Drug-Frovatriptan Succinate

Author Affiliations

  • 1 Chemical Process Research Laboratory, USV Limited, A.V. Gandhi Chowk, B.S.D. Marg, Govandi, Mumbai–400 088, MS, INDIA

Res. J. of Pharmaceutical Sci., Volume 2, Issue (5), Pages 1-10, June,30 (2013)


Frovatriptan succinate (FS) is administrated in monohydrate form. A new dihydrate form of FS is crystallized using acetone and water solvent combination. Interestingly, FS can be crystallized as monohydrate and dihydrate using acetone and water solvent combination. The process conditions are studied and optimized w.r.t. temperature of crystallization and % concentration of water, to get the desired hydrate. The result showed that the concentration of water is deciding factor for the formation of monohydrate and dihydrate of FS. Two different anhydrous forms were produced from two hydrates, by solvent mediated and solid-state transformation techniques. Effect of relative humidity on the anhydrous forms is also investigated. On exposure to humidity both the anhydrous forms are found to be unstable and convert to their corresponding hydrated form. Two hydrated forms and the two anhydrous forms obtained are characterized using X-Ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and Fourier Transform Infra-red (FTIR).


  1. Brittain H.G. (Ed.), Polymorphism in Pharmaceutical Solids, Marcel Dekker, New York (1999)
  2. Hilfiker R., Polymorphism in pharmaceutical Industry, Wiley-VCH (2006)
  3. Vippaguntaa S.R., Brittain H.G. and Grant D.J.W., Crystalline Solids, Adv. Drug Del. Rev., 48, 3-26 (2001)
  4. Henck J.O., Griesser U.J., and Bruger A., Polymorphie von Arzneistoffen. Eine wirtschaftliche Herausforderung, Pharm. Ind., 59, 165–169 (1997)
  5. Karpinski P.H., Polymorphism of Active Pharmaceutical Ingredients, Chem. Eng. Technol., 29, 233-237 (2006)
  6. Bugay D.E., Characterization of the solid-state: spectroscopic techniques, Adv. Drug Del. Rev., 48, 43-65 (2001)
  7. Raw A.S., Furness M.S., Gill D.S., Adams R.C., Holcombe Jr. F.O. and Yu L.X., Regulatory considerations of pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs), Adv. Drug Del. Rev., 56, 397-414 (2004)
  8. Bauer J., Spanton S., Henry R., Quick J., Dziki W., Porter W. and Morris J., Ritonavir: An Extraordinary Example of Conformational Polymorphism, Pharm. Res., 18, 859-866 (2001)
  9. Byrn S., Pfeiffer R., Ganey M., Hoiberg C. and Poochikian G., Pharmaceutical solids: a strategic approach to regulatory considerations, Pharm. Res., 12, 945-954 (1995)
  10. Yu L.X., Furness M.S., Raw A., Outlaw K.P.W., Nashed N. E., Ramos E., Miller S.P.F, Adams R.C., Fang F., Patel R.M., Holcombe Jr. F.O., Chiu Y.Y. and Hussain A.S., Scientific Considerations of Pharmaceutical Solid Polymorphism in Abbreviated New Drug Applications, Pharm. Res., 20, 531-536 (2003)
  11. Cimarosti Z., Castagnoli C., Rossetti M., Scarati M., Day C., Johnson B. and Westerduin P., Development of Drug Substances as Mixture of Polymorphs: Studies to Control Form 3 in Casopitant Mesylate, Org. Process Res. Dev., 14, 1337-1346 (2010)
  12. Lionberger R. A., Lee S. L., Lee L., Raw A. and Yu L.X., Quality by Design: Concept for ANDAs, Am. Ass. Pharm. Sci. J., 10, 268-276 (2008)
  13. Aguiar A. J., John Krc. Jr., Kinkel A. W. and Samyn J. C., Effect of polymorphism on the absorption of chloramphenicol from chloroamphenicol maleate, J. Pharm. Sci., 56, 847-853 (1967)
  14. Kobayashi Y., Ito S., Itai S. and Yamamoto K., Phtsicochemical properties and bioavailability of carbamazepine polymorphs and dihydrate, Int. J. Pharm., 193,137-146 (2000)
  15. Lee A. Y., Erdemir D. and Myerson A. S., Crystal polymorphism in chemical process development, Annu. Rev. Chem. Biomol. Eng., 2, 259-280 (2011)
  16. Huang L. F. and Qin (Tony) Tong W., Impact of solid state properties on developability assessment of drug candidates, Adv. Drug Del. Rev., 56, 321-334 (2004)
  17. Vishweshwar P., McMahon J.A., Oliveira M., Peterson M.L. and Zaworotko M.J., The predicatably Elusive Form II of Aspirin, J. Am. Chem. Soc., 127, 16802-16803 (2005)
  18. Thallapally P.K., Jetti R.K.R., Katz A.K., Carrell H.L., Singh K., Lahiri K., Kotha S., Boese R. and Desiraju G R., Polymorphism of 1,3,5-Trinitrobenzene Induced by a trisindane additive, Angew. Chem., 116,1169 (2004) Angew. Chem. Int. Ed. 43, 1149-1155 (2004)
  19. David W. I. F., Shankland K., Pulham C. R., Blagden N., Davey R. J. and Song M., Polymorphism in Benzamide, Angew. Chem., 117, 7194 (2005). Angew. Chem. Int. Ed., 44, 7032-7035 (2005)
  20. Day G.M., Trask A.V., Motherwell W.D.S. and Jones W., Investigting the latent polymorphism of maleic acid, Chem. Commun., 54-56 (2006)
  21. Gaonkar S.L., Mahendra M., Nanjunda S. S. and Shetty N. S., synthesis and crystal structure studies of Diethyl-(6-chloro-2-carbazolyl)methyl malonate an intermediate in the synthesis of Anti-inflammatory drug Carprofen, Res. J. Pharmaceutical Sci., 1(1), 16-22 (2012)
  22. Chaturvedula V.S.P and Indra P., Isolation and structural characaterization of lupane Triterpenes from polypodium vulgare, Res. J. Pharmaceutical Sci., 1(1), 23-27 (2012)
  23. (2013)
  24. Borrett G. T., Kitteringham J., Shipton M. R., Vimal M. and Young R.C., Enantiomers of carbazole derivatives as 5-HT1-lke agonists, U.S. Patent 5,616,603. Apr 1, (1997)
  25. Stahly G. P., Diversity in single- and multiple- componet crystals. The search for and prevalence of polymorphs and Cocrystals, Cryst. Growth Des., 7, 1007-1026 (2007)
  26. Zhang G.G.Z., Law D., Schmitt E.A. and Qiu Y., Phase transformation considerations during process development and manufacture of solid oral dosage forms, Adv. Drug Del. Rev., 56, 371-390 (2004)
  27. Christopher D. and Ronald J.O., Indole derivative. U.S.Patent 7, 238, 723 B2, Jul 3, (2007)
  28. Giron D., Goldbronn Ch., Mutz M., Pfeffer S. and Piechon Ph., Solid State Characterizations of Pharmaceutical Hydrates, J. of Therm. Anal. Cal., 68, 453-465 (2002)
  29. Albers D., Galgoci M., King D., Miller D., Newman R., Peerey L., Tai E. and Wolf R., Characterization of the polymorphic behavior of an organic compound using a dynamic thermal and X-ray powder diffraction technique, Org. Process Res. Dev., 11, 846-860 (2007)
  30. Haleblian J.K., Characterization of habits and crystalline modification of solid and their pharmaceutical applications, J. Pharm. Sci., 64, 1269-1288 (1975)
  31. Lutker K.M., Quinones R., Xu J., Ramamoorthy A. and Matzger A. J., Polymorphs and hydrates of acyclovir, J. Pharm. Sci., 100, 949-963 (2011)
  32. Behera A. L., Sahoo S K. and Patil S.V., Enhancement of solubility: A Pharmaceutical overview, Der Pharmaci Lett., 2, 310-318 (2010)
  33. Brown J., monohydrate lisinopril, U.S.patent 6, 465, 615 (2002)