title: Improvement in Dissolution Rate of Cefuroxime Axetil by using Poloxamer 188 and Neusilin US2.
abstract: A combination of fusion and surface adsorption techniques was used to enhance the dissolution rate of cefuroxime axetil. Solid dispersions of cefuroxime axetil were prepared by two methods, namely fusion method using poloxamer 188 alone and combination of poloxamer 188 and Neusilin US2 by fusion and surface adsorption method. Solid dispersions were evaluated for solubility, phase solubility, flowability, compressibility, Kawakita analysis, Fourier transform-infrared spectra, differential scanning calorimetry, powder X-ray diffraction study, in vitro drug release, and stability study. Solubility studies showed 12- and 14-fold increase in solubility for solid dispersions by fusion method, and fusion and surface adsorption method, respectively. Phase solubility studies showed negative ΔG (0) tr values for poloxamer 188 at various concentrations (0, 0.25, 0.5, 0.75 and 1%) indicating spontaneous nature of solubilisation. Fourier transform-infrared spectra and differential scanning calorimetry spectra showed that drug and excipients are compatible with each other. Powder X-ray diffraction study studies indicated that presence of Neusilin US2 is less likely to promote the reversion of the amorphous cefuroxime axetil to crystalline state. in vitro dissolution studies, T50% and mean dissolution time have shown better dissolution rate for solid dispersions by fusion and surface adsorption method. Cefuroxime axetil release at 15 min (Q15) and DE15 exhibited 23- and 20-fold improvement in dissolution rate. The optimized solid dispersion formulation was stable for 6 months of stability study as per ICH guidelines. The stability was ascertained from drug content, in vitro dissolution, Fourier transform-infrared spectra and differential scanning calorimetry study. Hence, this combined approach of fusion and surface adsorption can be used successfully to improve the dissolution rate of poorly soluble biopharmaceutical classification system class II drug cefuroxime axetil.
authors.affiliation: Department of Pharmaceutics, Roland Institute of Pharmaceutical Sciences, Ambapua, Khodasingi, Berhampur 760 010, India.
authors.forename: J
authors.initials: J
authors.lastname: Sruti
authors.forename: Ch N
authors.initials: ChN
authors.lastname: Patra
authors.forename: S K
authors.initials: SK
authors.lastname: Swain
authors.forename: S
authors.initials: S
authors.lastname: Beg
authors.forename: H R
authors.initials: HR
authors.lastname: Palatasingh
authors.forename: S C
authors.initials: SC
authors.lastname: Dinda
authors.forename: M E Bhanoji
authors.initials: ME
authors.lastname: Rao
keywords: Fusion method; Kawakita analysis; solubility enhancement; surface adsorption
references.citation: Pharm Dev Technol. 2009;14(4):373-9
references.pmid: 19552551
references.citation: J Pharm Pharmacol. 1975 Jan;27(1):48-9
references.pmid: 235616
references.citation: Pharm Acta Helv. 1996 Oct;71(4):229-35
references.pmid: 8921741
references.citation: J Pharm Sci. 1967 Oct;56(10):1243-52
references.pmid: 6059441
references.citation: Pharm Dev Technol. 2001 Nov;6(4):563-72
references.pmid: 11775957
references.citation: J Pharm Sci. 1999 Oct;88(10):1058-66
references.pmid: 10514356
references.citation: Int J Pharm. 2002 Sep 5;244(1-2):87-98
references.pmid: 12204568
references.citation: Drug Dev Ind Pharm. 2004 Jan;30(1):65-74
references.pmid: 15000431
references.citation: AAPS PharmSciTech. 2008;9(1):100-4
references.pmid: 18446468
references.citation: Int J Pharm. 2007 Oct 1;343(1-2):228-37
references.pmid: 17597315
references.citation: Colloids Surf B Biointerfaces. 2010 Mar 1;76(1):170-8
references.pmid: 19945828
references.citation: Int J Pharm. 2005 Aug 11;299(1-2):167-77
references.pmid: 15996838
references.citation: Drug Dev Ind Pharm. 2000 Nov;26(11):1141-50
references.pmid: 11068687
references.citation: Indian J Pharm Sci. 2011 Mar;73(2):243-7
references.pmid: 22303074
references.citation: Eur J Pharm Sci. 2002 Feb;15(1):71-8
references.pmid: 11803133
references.citation: AAPS PharmSciTech. 2009;10(4):1206-15
references.pmid: 19862626
references.citation: Eur J Pharm Biopharm. 2000 Jul;50(1):47-60
references.pmid: 10840192
references.citation: Pharm Dev Technol. 2008;13(3):255-69
references.pmid: 18484494
references.citation: Eur J Pharm Biopharm. 2010 Oct;76(2):215-21
references.pmid: 20603215
references.citation: Pharm Res. 2006 Oct;23(10):2317-25
references.pmid: 16927179