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Polymer-directed Crystallization of Sibutramine using Cellulose Derivatives

  • Bae, Ha-Rim (Department of Chemical Engineering and Materials Science, Chung-Ang University) ;
  • Lee, Hye-Seung (Department of Chemical Engineering and Materials Science, Chung-Ang University) ;
  • Lee, Min-Kyung (Department of Chemical Engineering and Materials Science, Chung-Ang University) ;
  • Lee, Jong-Hwi (Department of Chemical Engineering and Materials Science, Chung-Ang University)
  • Received : 2010.12.02
  • Accepted : 2011.01.27
  • Published : 2011.02.20

Abstract

Nonclassical pathway of crystallization has been utilized to modify the properties and morphologies of inorganic and organic/inorganic materials. In here, the polymer-directed crystallization method has been applied to the pharmaceutical active ingredient to assess the applicability for as a particle engineering tool. The polymer-directed crystallization was successful to modifying the crystal size, habit and morphology, but it was not effective to discover the novel polymorphs of Sibutramine (SB). SB was selected as a model drug and polyacrylic acid (PAA), polyethylene imine (PEI) and chitosan (CHI) were added as a crystallization pathway modifier. SB was crystallized via drowning crystallization using methanol or ethanol as a solvent and water as a non-solvent. The significant interactions between polymer and the drug were confirmed by measuring the solubility of the drug in presence of polymer during the crystallization. The crystal forms of SB are characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) and optical microscope (OM). The polymer-directed crystallization seems to be able to modify the crystal properties of pharmaceutical active ingredient, which is critical in determining the bioavailability, processability, and stability.

References

  1. Adam, L.G., Adam, J. M., 2007. New form discovery for the analgesics flurbiprofen and sulindac facilitated by polymerinduced heteronucleation. J. Pharm. Sci. 96, 2978-2986. https://doi.org/10.1002/jps.20954
  2. Brittain, H.G., Grant, D.J.W., 1999. Effects of polymorphism and solid-state solvation on solubility and dissolution rate. In: Swarbrick, J. (Ed.), Polymorphism in Pharmaceutical Solids. Marcel Dekker, New York, pp. 279-330.
  3. Chao, R.S., Vail, K.C., 1987. Polymorphism of 1,2-dihydro-6-neopentyl-2-oxonicotinic acid: characterization, interconversion, and quantitation. Pharm. Res. 4, 429-432. https://doi.org/10.1023/A:1016498731952
  4. Grzesiak, A.L., Matzger, A.J., 2007. Selection and discovery of polymorphs of platinum complexes facilitated by polymerinduced heteronucleation. Inorg. Chem. 46, 453-457. https://doi.org/10.1021/ic061323k
  5. Grzesiak, A.L., Uribe, F.J., Ockwig, N.W., Yaghi, O.M.,Matzger, A.J., 2006. Polymer-induced heteronucleation for the discovery of new extended solids. Angew. Chem. Int. Edit 45, 2553-2556. https://doi.org/10.1002/anie.200504312
  6. Lang, M., Grzesiak, A.L., Matzger, A.J., 2002. The use of polymer heteronuclei for crystalline polymorph selection. J. Am. Chem. Soc. 124, 14834-14835. https://doi.org/10.1021/ja0286526
  7. Price, C.P., Grzesiak, A.L., Kampf, J.W., Matzger, A.J., 2003. Maize 1: A trimorphic azo pigment. Cryst. Growth Des. 3, 1021-1025. https://doi.org/10.1021/cg025610k
  8. Price, C.P., Grzesiak, A.L., Lang, M., Matzger, A.J., 2002. Polymorphism of abumetone. Cryst. Growth Des. 2, 501-503. https://doi.org/10.1021/cg0255568
  9. Price, C.P., Grzesiak, A.L., Matzger, A.J., 2005. Crystalline polymorph selection and discovery with polymer heteronuclei. J. Am. Chem. Soc. 127, 5512-5517. https://doi.org/10.1021/ja042561m
  10. Rodriguez-Spong, B., Price, C.P., Jayasankar, A., Matzger, A.J., Rodriguez-Hornedo, N., 2004. Generalprinciples of pharmaceutical solid polymorphism: A supramolecular perspective. Adv. Drug Delivery Rev. 56, 241-274. https://doi.org/10.1016/j.addr.2003.10.005
  11. Tiwary, A.K., 2001. Modification of crystal habit and its role in dosage form performance. Drug Dev. Ind. Pharm. 27, 699-709. https://doi.org/10.1081/DDC-100107327