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 1: INTRODUCTION1.0 BackgroundOver <strong>the</strong> l<strong>as</strong>t three decades <strong>hot</strong>-<strong>melt</strong> <strong>extrusion</strong> (HME) h<strong>as</strong> emerged <strong>as</strong> an influentialprocessing technology in developing molecular dispersions <strong>of</strong> active pharmaceutical ingredients(APIs) into polymer matrices and h<strong>as</strong> already been demonstrated to provide time controlled,modified, extended and targeted drug delivery resulting in improved bioavailability [1, 2, 3, 4] .HME h<strong>as</strong> now provided opportunity <strong>for</strong> use <strong>of</strong> materials in order to m<strong>as</strong>k <strong>the</strong> bitter t<strong>as</strong>te <strong>of</strong>active substances [4] . Since <strong>the</strong> industrial application <strong>of</strong> <strong>the</strong> <strong>extrusion</strong> process back in <strong>the</strong> 1930‘s,HME h<strong>as</strong> received considerable attention from both <strong>the</strong> pharmaceutical industries and academiain a range <strong>of</strong> applications <strong>for</strong> pharmaceutical dosage <strong>for</strong>ms, such <strong>as</strong> tablets, capsules, films andimplants <strong>for</strong> drug delivery via oral, transdermal and transmucosal routes [5] . This makes HME anexcellent alternative to o<strong>the</strong>r conventionally available <strong>technique</strong>s such <strong>as</strong> solvent evaporation,freeze drying, spray drying and so on (Table 1.1). In addition to being a proven manufacturingprocess, HME meets <strong>the</strong> goal <strong>of</strong> <strong>the</strong> US Food and Drug Administration's (FDA) processanalytical technology (PAT) scheme <strong>for</strong> designing, analyzing <strong>as</strong> well <strong>as</strong> controlling <strong>the</strong>manufacturing process via quality control me<strong>as</strong>urements during active <strong>extrusion</strong> process [6] . Inthis chapter, <strong>the</strong> <strong>hot</strong>-<strong>melt</strong> <strong>extrusion</strong> <strong>technique</strong> is reviewed b<strong>as</strong>ed on a holistic perspective <strong>of</strong> itsvarious components, processing technologies <strong>as</strong> well <strong>as</strong> <strong>the</strong> materials and <strong>novel</strong> <strong>for</strong>mulationdesign and developments in its varied applications in oral drug delivery systems.1.1 Hot-<strong>melt</strong> <strong>extrusion</strong> (HME): Process technologyJoseph Brama first invented <strong>the</strong> <strong>extrusion</strong> process <strong>for</strong> <strong>the</strong> manufacturing <strong>of</strong> lead pipes at<strong>the</strong> end <strong>of</strong> <strong>the</strong> eighteenth century [7] . Since <strong>the</strong>n, it h<strong>as</strong> been used in <strong>the</strong> pl<strong>as</strong>tic, rubber and foodmanufacturing industry to produce items ranging from pipes to sheets and bags. With <strong>the</strong> advent<strong>of</strong> high throughput screening, currently more than half <strong>of</strong> all pl<strong>as</strong>tic products including bags,sheets, and pipes are manufactured my HME and <strong>the</strong>re<strong>for</strong>e various polymers have been used to<strong>melt</strong> and <strong>for</strong>m different shapes <strong>for</strong> a variety <strong>of</strong> industrial and domestic applications. Thetechnology h<strong>as</strong> proven to be a robust method <strong>of</strong> producing numerous drug delivery systems and<strong>the</strong>re<strong>for</strong>e it h<strong>as</strong> been found to be useful in <strong>the</strong> pharmaceutical industry <strong>as</strong> well [8] . Extrusion is <strong>the</strong>process <strong>of</strong> pumping raw materials at elevated controlled temperature and pressure through aheated barrel into a product <strong>of</strong> uni<strong>for</strong>m shape and density [9] . Breitenbach first introduced <strong>the</strong>development <strong>of</strong> <strong>melt</strong> <strong>extrusion</strong> process in pharmaceutical manufacturing operationshowever, Follonier and his co-workers first examined <strong>the</strong> <strong>hot</strong> <strong>melt</strong> technology to manufacture1 | P a g e[10] ,