Development of hot-melt extrusion as a novel technique for the ...

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17. Woertz K,Tissen C, Kleinebudde P, Breitkreutz J. Performance qualification of anelectronic tongue based on ICH guideline Q2. J Pharm Biomed Anal. 2010; 51: pp.497–506.18. Hansen CM. The universality of the solubility parameter. Ind Eng Chem Res Dev.1969; 8: 2-11.19. Hoftyzer PJ, VanKrevelen DW. Properties of polymers, Elsevier, Amsterdam, 1976.20. Bagley EB, Nelson TP & Scigliano JM. Three-dimensional solubility parameters andtheir relationship to internal pressure measurements in polar and hydrogen bondingsolvents. J Paint Technol. 1971; 43: 35-42.21. Maniruzzaman M, Rana MM, Boateng JS, Mitchell JC, Douroumis D. Dissolutionenhancement of poorly water-soluble APIs processed by hot-melt extrusion usinghydrophilic polymers. Drug Dev Ind Pharm. 2012. In press.22. Zheng X, Yang R, Tang X and Zheng L. Part I: Characterization of Solid Dispersionsof Nimodipine Prepared by Hot-melt Extrusion. Drug Dev Ind Pharm. 2007; 33:791–802.23. Greenhalgh DJ, Peter W, York TP. Solubility parameters as predictors of miscibilityin solid dispersions, J Pharm Sci. 1999; 88: 1182–1190.24. Breitkreutz J. Prediction of intestinal drug absorption properties by three dimensionalsolubility parameters. Pham Res. 1998; 15:1370-1375.25. Albers J. Hot-melt Extrusion with Poorly Soluble Drugs. Heinrich-Heine- UniversitatDusseldorf, Germany. 2008.26. Forster A, Hempenstall J, Tucker I, Rades T. Selection of excipients for meltextrusion with two poorly water-soluble drugs by solubility parameter calculation andthermal analysis. Int J Pharm. 2001; 226 (1–2):147–161.27. Gryczke A. Innovative Formulations by Melt Extrusion with EUDRAGIT®Polymers. RÖHM GmbH & Co. KG, Darmstadt. 2005.28. Guidance for Industry. Dissolution Testing of Immediate Release Solid Oral DosageForms U.S. Department of Health and Human Services Food and DrugAdministration, Center for Drug Evaluation and Research (CDER). 1997.105 | P a g e
CHAPTER 6: DRUG-POLYMER INTERMOLECULAR INTERACTIONS IN HOT-MELT EXTRUDED SOLID DISPERSIONS1. IntroductionOver the last decades hot-melt extrusion (HME) has emerged as an influentialprocessing technology in developing solid dispersions of active pharmaceutical ingredients(APIs) into polymer matrices and has already been demonstrated to provide time controlled,modified, extended and targeted drug delivery resulting in improved bioavailability [1, 2] . Theformation of active solid dispersions through HME and therefore configuration of complexesdue to macromolecular orientational relations in polymer networks has been of great interestin pharmaceutical research and development. Polymer complexes are classified by the natureof the association. The major classes of polymer complexes are the stereocomplexes,intermolecular hydrogen-bonded complexes and polyelectrolyte complexes [3,4] .The polyelectrolytedrug complexes have been the focus of several researchers andstill very limited data is available concerning the understanding of the underlyingmechanisms involved in the formation of drug-polyion complexes [5] . Different techniqueshave already been reported successfully to describe various drug-polymer interactions andanalyse the drug-polyelectrolyte complexes. Pavli et al. described oppositely chargeddoxazosin mesylate (DM), a cationic drug and polyelectrolytes carrageenans interaction byspecial DM ion-selective membrane electrode methods constructing the binding isothermstreated by the ZimmBragg theory and cooperative binding model [5] . Some other techniqueswhich have already been established to analyse drug-polymers interactions are the dialysisequilibrium technique [6, 7] , Fourier transform infra-red spectroscopy (FTIR) and UVspectroscopy [8, 9] , solid state NMR [10] , drug–polymer interaction parameter model 11 andmore importantly x-ray photo electron spectroscopy [10, 12] .The X-ray photoelectron spectroscopy (XPS) can be employed as a valuable tool forthe characterisation of polymer surfaces and it has made a significant contribution to theinvestigation of biomedical polymers but most importantly provides a quantitative elementalanalysis and also information on the chemical bonding within the surface layers of thepolymer as well as the prediction of the changes onto the material surface [10] . The increasingimportance of XPS for many types of intermolecular interactions based analysis arises forseveral reasons; such as it can provide information about the actual composition and chemicalstate of surfaces and interfaces that dominate properties of interacting materials even in nano106 | P a g e
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DECLARATION“I certify that this w
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taste masking effect of the process
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CHAPTER 2: DISSOLUTION ENHANCEMENT
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3.2 Powder and ODT characterization
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3.7 In vitro drug release profiles
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3.1 Solubility parameters and extru
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polymers.7.2 DSC findings of all AP
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2.4b Diffractograms of FMT formulat
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4.3 Schematic representation of the
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55 exrudates (b) DPD/L100-55 PM (c)
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8.5d A plot of the logarithm of HCS
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L100Eudragit L100L100-55 Eudragit L
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Maniruzzaman M, Rai D, Boateng JS.
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Maniruzzaman M, Boateng JS, Bonnefi
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CHAPTER 1: INTRODUCTION1.0 Backgrou
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Table 1.1: HME and other convention
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homogenize but also compress the ex
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properties of polymers and excipien
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particles‘ wettability [46] . A v
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Table 1.2: Different hot-melt extru
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1.8 Aims and objectivesThe purpose
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29. Zheng X, Yang R, Tang X and Zhe
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56. International Conference on Har
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CHAPTER 2: DISSOLUTION ENHANCEMENT
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Fdid ,Vi F2pip , p( Ehi/ ViVi )i =
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used. Each sample was scanned from
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Furthermore, by means of thermodyna
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3.2 Particle size morphology and pa
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Fig. 2.4a: Diffractograms of INM fo
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However, the DSC thermograms of the
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Fig. 2.5b: DSC thermograms of INM a
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Fig. 2.5e: DSC thermograms of FMT a
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Nevertheless, more than 80% FMT was
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6. Caron V, Tajber L, Corrigan OI,
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CHAPTER 3: DEVELOPMENT AND EVALUATI
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2.2 Hot-Melt extrusionHot-melt extr
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Committee of the University of Gree
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The PM of formulation II (40% IBU)
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Fig. 3.3: DSC thermograms of pure I
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As a general rule, the powder compr
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Fig. 3.4: Schematic diagram of ODT
Page 88 and 89: Fig. 3.5: Schematic diagram of ODTs
Page 90 and 91: Fig. 3.7: Schematic diagram of ODTs
Page 92 and 93: F2 0 0.5 0 1 0 1F6 0 0.5 0 1 0 2F7
Page 94 and 95: 6. M.F. Al-Omran, S.A. Al-Suwayeh,
Page 96 and 97: 30. L. Saerens, L. Dierickx, B. Len
Page 98 and 99: leading to significant variations w
Page 100 and 101: 2.6. In vitro drug release studiesI
Page 102 and 103: v2d 2p(4.1)Table 4.1: Calculated so
Page 104 and 105: The observed melting peaks are shif
Page 106 and 107: Fig. 4.2a: Powder XRPD patterns of
Page 108 and 109: Interestingly, no difference was ob
Page 110 and 111: 7 Astree sensors Taste masking effi
Page 112 and 113: The in vitro e-tongue evaluation wa
Page 114 and 115: 3. K. Woertz, C. Tissen, P. Kleineb
Page 116 and 117: 25. B.C. Hancock, P. York, R.C. Row
Page 118 and 119: CHAPTER 5: AN IN VIVO AND IN VITRO
Page 120 and 121: (dispersion forces and polarization
Page 122 and 123: Table 5.1: Sample preparation for t
Page 124 and 125: Table 5.2: Solubility parameters ca
Page 126 and 127: Physical mixtures (PM) and extruded
Page 128 and 129: Fig. 5.2c: Thermograms of CTZ and V
Page 130 and 131: masking effect for active concentra
Page 132 and 133: Fig. 5.5b: Distance and discriminat
Page 134 and 135: Table 5.4: Mean standard deviation
Page 136 and 137: Fig. 5.6b: Release profiles of VRP
Page 140 and 141: scale or lower. XPS is more accurat
Page 142 and 143: patterns were identified after ener
Page 144 and 145: 3.3 Differential scanning calorimet
Page 146 and 147: Fig. 6.3a: Diffractograms of PRP fo
Page 148 and 149: good agreement with the anticipated
Page 150 and 151: Since L100 contained higher proport
Page 152 and 153: at ~533.01 eV is the combination of
Page 154 and 155: Finally, the XPS analysis confirmed
Page 156 and 157: Fig. 6.6b: 1 H NMR spectra of all P
Page 158 and 159: 6) Bonferoni, M.C.; Rossi, S.; Ferr
Page 160 and 161: 26) Vandencasteele, N.; Reniers, F.
Page 162 and 163: Gibbs free energy change before and
Page 164 and 165: 2.5 Hot-melt extrusion (HME) proces
Page 166 and 167: 2.11 X-ray photoelectron spectrosco
Page 168 and 169: Table 7.2: DSC findings of all APIs
Page 170 and 171: 3.4 In vivo and in vitro taste mask
Page 172 and 173: Fig. 7.3c: Normalised DI (%) of all
Page 174 and 175: Table 7.4: Binding energy calculati
Page 176 and 177: PRP/ polymers extruded in compariso
Page 178 and 179: atom as NH + 4 . This observed N 1s
Page 180 and 181: 8.0 ConclusionsThe presence of inte
Page 182 and 183: 20. Davies MC, Wilding IR, Short RD
Page 184 and 185: CHAPTER 8: SUSTAINED RELEASE HYDROC
Page 186 and 187: 2.3 Preparation of formulation blen
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medium pH was maintained as 1.2 by
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Fig. 8.1: SEM images of [(a), (b)]
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Fig. 8.2b: DSC transitions of HCS/E
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in the range of 10-12 kP. However,
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ate and time on the basis of Eq. (8
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Fig. 8.5c: A plot of the cubic root
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when n > 0.89. From the results of
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14. Lam PL, Lee KKH,Wong RSM, Cheng
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Furthermore, HME has successfully b
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Supp. Fig. 2: XPS O 1s peaks for PR
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Supp. Fig. 4: O 1s BE peaks for L10
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8.2 s 6.2 s 3.8 s 1.8 s 200 msS
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12.2 s 9.0 s 6.2 s 3.8 s 1.8 s
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Supplementary table 1: Solubility p
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N = 55000/ 219.2 = 250.912Density:
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(4) Eudragit L100, N = (125000/202
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