Development of hot-melt extrusion as a novel technique for the ...
Development of hot-melt extrusion as a novel technique for the ...
Development of hot-melt extrusion as a novel technique for the ...
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4.0 ConclusionsIn <strong>the</strong> current chapter HME processing w<strong>as</strong> employed <strong>as</strong> a means to incre<strong>as</strong>e <strong>the</strong>dissolution rates <strong>of</strong> two water insoluble drugs. INM and FMT were extruded with SOL, VA64and S630 at different loadings up to 40% without <strong>the</strong> presence <strong>of</strong> traditional pl<strong>as</strong>ticizers. The<strong>extrusion</strong> process w<strong>as</strong> optimized to produce amorphous solid dispersions <strong>of</strong> <strong>the</strong> drug substances.Fur<strong>the</strong>r physico-chemical characterization studies confirmed <strong>the</strong> <strong>the</strong>oretical drug – polymermiscibility <strong>for</strong> all binary mixtures <strong>as</strong> predicted by Greenhalgh and Bagley approaches. Inaddition, INM and FMT demonstrated pl<strong>as</strong>ticization effects and were found to be molecularlydispersed within <strong>the</strong> polymer matrices. Incre<strong>as</strong>ed aqueous solubility w<strong>as</strong> observed in both APIsmixtures with all three polymers and <strong>the</strong> extruded solid dispersions resulted in greaterdissolution rates over <strong>the</strong> bulk drugs.There<strong>for</strong>e, through <strong>the</strong> appropriate selection <strong>of</strong> a polymeric carrier solid dispersions <strong>of</strong>both INM and FMT can be prepared by <strong>hot</strong>-<strong>melt</strong> <strong>extrusion</strong> to improve <strong>the</strong> dissolution properties<strong>of</strong> <strong>the</strong> poorly water-soluble drugs. Fur<strong>the</strong>r work is warranted to determine whe<strong>the</strong>r <strong>the</strong> oralbioavailability <strong>of</strong> INM/FMT is incre<strong>as</strong>ed <strong>for</strong> <strong>the</strong> solid dispersions with enhanced dissolutioncharacteristics.5.0 References1. Leuner C & Dressman J. Improving drug solubility <strong>for</strong> oral delivery using soliddispersions. Eur J Pharm Biopharm 2000; 50: 47–60.2. Hong SW, Lee BS, Park SJ, Jeon HR, Moon KY, Kang MH, Park SH, Choi SU, SongWH, Lee J, Choi YW. Solid dispersion <strong>for</strong>mulations <strong>of</strong> megestrol acetate withcopovidone <strong>for</strong> enhanced dissolution and oral bioavailability. Arch Pharm Res 2011;34(1):127-35.3. Dittgen M, Fricke S, Gerecke H, Osterwald H. Hot spin mixing: a new technology tomanufacture solid dispersions. Pharmazie 1995; 50(3): 225–226.4. Breitenbach J. Melt <strong>extrusion</strong>: from process to drug delivery technology. Eur J PharmBiopharm 2002; 54(2): 107–117.5. Sekikawa H, Fukyda W, Takada M, Ohtani K, Arita T, Nakano M. Dissolution behaviorand g<strong>as</strong>trointestinal absorption <strong>of</strong> dicumarol from solid dispersion systems <strong>of</strong> dicumarolpolyvinylpyrrolidineand dicumarol-beta-cyclodextrin. Chem Pharm Bull 1983; 31(4):1350–1356.38 | P a g e