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

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26) Vandencasteele, N.; Reniers, F. Plasma-modified polymer surfaces: Characterizationusing XPS. Journal of Electron Spectroscopy and Related Phenomena. 2010, 178–179, 394–408.27) Ghods, P.; Isgor, O.B.; Brown, J.R.; Bensebaa, F.; Kingston, D. XPS depth profilingstudy on the passive oxide film of carbon steel in saturated calcium hydroxidesolution and the effect of chloride on the film properties. Applied Surface Science,2011, 257, 4669–4677.28) Sabbatini, L.; Zambonin, P. G. XPS and SIMS surface chemical analysis of someimportant classes of polymeric biomaterials. Journal of Electron Spectroscopy andRelated Phenomena, 1996, 81, 285-301.29) A.Gryckze.Degussatechnical brochure (Melt Extrusion with Eudragit). Germany.200630) Brettmann, B.; Bell, E.; Myerson, A.; Trout, B. Solid-State NMR Characterization ofHigh-Loading Solid Solutions of API and Excipients Formed by Electrospinning.Pharmaceutical Nanotechnology. 2012, 101, 1538-1545.31) Qi, S.; Belton, P.; Nollenberger, K.; Clayden, N.; Reading, M.; Craig, D. Q. M. Novelcharacterisation of phase separation in hot melt extruded solid dispersions: a thermal,microscopic and NMR relaxometry study. Pharm Res. 2010, 27, 1869–83.32) Qi. S.; Gryczke, A.; Belton, P.; Craig, D. Q. M. Characterisation of solid dispersionsof paracetamol and EUDRAGIT® E prepared by hotmelt extrusion using thermal,microthermal and spectroscopic analysis. Int J Pharm. 2008, 354, (1–2):158–67.127 | P a g e
CHAPTER 7: EVALUATION OF THE INTERRELATION BETWEENINTERMOLECULAR INTERACTIONS AND TASTE MASKING EFFICIENCY OFTWO ANIONIC POLYMERS IN MELT EXTRUDED SOLID DISPERSIONS1.0 IntroductionTo date, masking the unpleasant taste of bitter APIs has been a real challenge forpatient compliance and therefore various taste masking approaches have already beendeveloped. The most commonly technologies are film casting by adding flavours orsweeteners [1,2] . Freeze-drying [2] , spary drying [4] , microencapsulation [5, 6] , fluidized bedcoating [2] , high shear mixing [7] and supercritical fluids [8] have also been reported to be usedfor taste-masking purposes. HME has been introduced as a novel approach to mask the tasteof bitter actives by enhancing drug-polymer interactions [9] .It has been reported in the literature that HME technique has successfully managed tomask the bitterness of ibuprofen and paracetamol through intermolecular forces (e.g.hydrogen bonding) between the active substance and the polymer matrix [2, 10] . In thesestudies the active substances were molecularly dispersed within the polymer matricesresulting effective taste masking of the drug‘s unpleasant taste. Solid lipid extrusion is alsoanother suitable HME approach to produce extrudates of bitter APIs with improved tasteproperties. Recently, Breitkreutz et al. developed taste masked lipid based formulation byextrusion with NXP 1210, a BCS class II drug (anti inflammatory) [11] .The taste masking evaluation of pharmaceutical dosage forms is evaluated both by invivo and/or in vitro taste analysis. For the in vitro taste masking analysis commerciallyavailable electronic tongues have been employed to evaluate the masking effect. The e -tongues demonstrate very good correlation with human taste panels, reproducibility, lowdetection limits and high sensitivity [12, 13] .Various techniques have already been reported successfully to describe various drugpolymersinteractions such as the dialysis equilibrium technique [14, 15] , UV spectroscopy[16, 17] , solid state NMR [18] , drug–polymer interaction parameter model [19] , Fourier TransformInfrared (FT-IR) and more importantly X-ray photo electron spectroscopy [16, 20] . X-rayphotoelectron spectroscopy (XPS) has proved a potent tool for the characterisation ofpolymer surfaces and it has made a significant contribution to the analysis of biomedicalpolymers. Similarly FT-IR has been accepted as sensitive technique to elucidate the structuralchanges in the active formulations [16] . The lattice-based Flory–Huggins (F–H) theory is awell known theory describing polymer–solvent or polymer–polymer interactions based on the128 | 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
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Fig. 3.5: Schematic diagram of ODTs
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Fig. 3.7: Schematic diagram of ODTs
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F2 0 0.5 0 1 0 1F6 0 0.5 0 1 0 2F7
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6. M.F. Al-Omran, S.A. Al-Suwayeh,
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30. L. Saerens, L. Dierickx, B. Len
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leading to significant variations w
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2.6. In vitro drug release studiesI
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v2d 2p(4.1)Table 4.1: Calculated so
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The observed melting peaks are shif
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Fig. 4.2a: Powder XRPD patterns of
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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 138 and 139: 17. Woertz K,Tissen C, Kleinebudde
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 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
Page 188 and 189: medium pH was maintained as 1.2 by
Page 190 and 191: Fig. 8.1: SEM images of [(a), (b)]
Page 192 and 193: Fig. 8.2b: DSC transitions of HCS/E
Page 194 and 195: in the range of 10-12 kP. However,
Page 196 and 197: ate and time on the basis of Eq. (8
Page 198 and 199: Fig. 8.5c: A plot of the cubic root
Page 200 and 201: when n > 0.89. From the results of
Page 202 and 203: 14. Lam PL, Lee KKH,Wong RSM, Cheng
Page 204 and 205: Furthermore, HME has successfully b
Page 206 and 207: Supp. Fig. 2: XPS O 1s peaks for PR
Page 208 and 209: 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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