Effect of Biopolymer on the Dissolution and Stability of Itraconazole

Abstract:

traconazole (ITZ) polyethylene glycol 4000 (PEG) solid dispersions (SDs) containing hydroxypropyl methylcellulose (HPMC) and/or low methoxy pectin (LMP) were prepared by melting method at a ratio of drug to carrier of 1:9. ITZPEG formulations showed the highest drug release (83.51%) when compared to the formulations containing HPMC and/or pectin (i.e., 43.02%, 40.64% and 59.94% for those containing HPMC, LMP and HPMC+LMP, respectively). Powder X-ray diffractograms of all formulations revealed that the drug was present in an amorphous form while a crystalline form was observed only in ITZ or its physical mixture. After storage at accelerated condition (40°C, 75%RH) for 2 and 12 months, the crystalline of ITZ was clearly not observed in all SDs. All formulations showed an increase in mean dissolution time (MDT) but the formulations containing biopolymer showed the lower MDT than that containing no biopolymer. The results suggested that either HPMC or LMP in SDs can help to inhibit the recrystallization of amorphous ITZ in SD, probably by a polymer anti-plasticizing effect.

• Periodical: Advanced Materials Research (Volume 747)
• Pages: 115-118
• DOI: https://doi.org/10.4028/www.scientific.net/AMR.747.115
• Online since: August 2013
• Authors: Benchawan Chamsai, Pornsak Sriamornsak
• Keywords: Biopolymer, Solid Dispersion, Traconazole (ITZ)

References

[1] G. Verreck, K. Six, G. Van den Mooter, L. Baert, J. Peeters, M.E. Brewster, Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion-part I, Int. J. Pharm. 251 (2003) 165-174.

DOI: 10.1016/s0378-5173(02)00591-4

[2] S. Janssens, H. Novoa de Armas, C. J. Roberts, G. Van den Mooter, Characterization of ternary solid dispersions of itraconazole, PEG 6000, and HPMC 2910 E5, J. Pharm. Sci. 97 (2008) 2110-2120.

DOI: 10.1002/jps.21128

[3] K.A. Overhoff, A. Moreno, D.A. Miller, K.P. Johnston, R.O. Williams III, Solid dispersions of itraconazole and enteric polymers made by ultra-rapid freezing, Int. J. Pharm. 336 (2007) 122-132.

DOI: 10.1016/j.ijpharm.2006.11.043

[4] S. Janssens, C. Roberts, E.F. Smith, G. Van den Mooter, Physical stability of ternary solid dispersions of itraconazole in polyethyleneglycol 6000/ hydroxypropyl methylcellulose 2910 E5 blends, Int. J. Pharm. 355 (2008) 100 -107.

DOI: 10.1016/j.ijpharm.2007.11.054

[5] F. Jijun, Z. Lili, G. Tingting, T. Xing, H. Haibing, Stable nimodipine tablets with high bioavailability containing NM-SD prepared by hot-melt extrusion, Powder Tech. 204 (2010) 214-221.

DOI: 10.1016/j.powtec.2010.08.003

[6] P. Sriamornsak, J. Nunthanid, M. Luangtana-anan, S. Puttipipatkhachorn, Alginate-based pellets prepared by extrusion/spheronization: A preliminary study on the effect of additive in granulating liquid, Eur. J. Pharm. Biopharm. 67 (2007) 227-235.

DOI: 10.1016/j.ejpb.2006.11.007