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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CHAPTER 2: DISSOLUTION ENHANCEMENT OF POORLY WATER-SOLUBLEAPIs PROCESSED BY HOT-MELT EXTRUSION (HME) USING HYDROPHILICPOLYMERS1.0 IntroductionWith <strong>the</strong> recent start <strong>of</strong> high throughput screening <strong>of</strong> potential <strong>the</strong>rapeutically activeingredients, <strong>the</strong> number <strong>of</strong> poorly soluble drug candidates h<strong>as</strong> incre<strong>as</strong>ed sharply (about 25% to40%). The availability <strong>of</strong> water insoluble APIs into systemic circulation is highly controlled anddependent on its aqueous solubility and <strong>the</strong>re<strong>for</strong>e incre<strong>as</strong>ing <strong>the</strong> solubility/dissolution <strong>of</strong> poorlysoluble subtances <strong>for</strong> oral delivery is a challenging t<strong>as</strong>k in pharmaceutical processing anddevelopment. The manufacture <strong>of</strong> solid dispersions is considered one <strong>of</strong> <strong>the</strong> most attractiveapproaches to incre<strong>as</strong>e solubility and thus bioavailability <strong>of</strong> poorly soluble APIs [1] . Soliddispersions have been prepared by employing various approaches such <strong>as</strong> co-evaporation [2] , <strong>hot</strong>spin mixing [3] , roll-mixing or co-milling [4] , freeze-drying [5] , spray drying [6,7] and supercriticalfluid processing (SFP) [8] .Hot-<strong>melt</strong> <strong>extrusion</strong> (HME) is considered <strong>as</strong> an effective process in pharmaceuticalindustry <strong>for</strong> <strong>the</strong> <strong>for</strong>mation <strong>of</strong> molecular dispersions in order to improve <strong>the</strong> bioavailabity <strong>of</strong> drugcomponents which have low water solubility [9] . The <strong>melt</strong> <strong>extrusion</strong> process <strong>of</strong>fers variousadvantages over conventional approaches such <strong>as</strong> it is a solvent-free process and <strong>the</strong>re<strong>for</strong>eenvironmental friendly. Relatively low heat sensitive substances can be e<strong>as</strong>ily processed byHME <strong>as</strong> <strong>the</strong> exposure <strong>of</strong> <strong>the</strong> APIs is very short and processing temperatures can be lowered byselecting <strong>the</strong> appropriate drug carrier. Moreover, <strong>the</strong> <strong>melt</strong> <strong>extrusion</strong> process helps to convertcrystalline active substances into <strong>the</strong> amorphous state <strong>as</strong> well <strong>as</strong> <strong>of</strong>fers a chance to dissolve <strong>the</strong>drugs in <strong>the</strong> inert polymer matrix through <strong>the</strong> <strong>for</strong>mation <strong>of</strong> solid solutions. Different c<strong>as</strong>e studieshave been reported to incre<strong>as</strong>e solubility <strong>of</strong> various poorly soluble drugs [10] by HME includingnifedipine, tolbutamide, lacidipine [11, 12] , itraconazole [13, 14] and nitrendipine [15] .Famotidine (FMT) is a histamine H2-receptor antagonist (H2RA) mainly used <strong>for</strong> <strong>the</strong>treatment <strong>of</strong> g<strong>as</strong>tric-duodenal ulcers, symptomatic g<strong>as</strong>tro-oesophageal reflux dise<strong>as</strong>e (GERD),erosive oesophagitis, management <strong>of</strong> hypersecretory conditions [16, 17] <strong>for</strong> paediatric populations[17] . According to <strong>the</strong> Biopharmaceutical Cl<strong>as</strong>sification System (BCS) FMT is cl<strong>as</strong>sified <strong>as</strong> acl<strong>as</strong>s IV drug (low solubility, low permeability) [18] . Indomethacin (INM) is a non-steroidal antiinflammatorydrug (NSAID) used to treat rheumatoid arthritis, osteoarthritis, alkylosing19 | P a g e