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

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2.4b Diffractograms of FMT formulations: pure FMT (inset), (a) FMT/S6303020% PM (b) FMT/S63020% E (c) FAM/SOL 20% PM (d) FMT/SOL20% E (e) FMT/SOL 40% PM (f) FMT/SOL 40% E (g) FMT/VA6420% PM (h) FMT/VA64 20% E (milling time 5 min at 400 rmp).2.5a MTDSC thermograms of pure polymers and drugs. 312.5b DSC thermograms of INM and VA64 (physical mixtures and33extrudates).2.5c DSC thermograms of INM and SOL (physical mixtures and extrudates). 332.5d DSC thermograms of INM and FMT with Plasdone S630 (physical34mixtures and extrudates).2.5e DSC thermograms of FMT and SOL (physical mixtures and extrudates). 352.6a Drug release profile of pure INM, INM/SOL 20%, INM/VA64 20%,36INM/S630 20%, INM/VA64 40% and INM/SOL 40%.2.6b Drug release profile of pure FMT, FMT/VA64 20%, FMT/SOL 20%36and FMT/S630 20%.CHAPTER 33.1 Particles size distribution of micronized IBU/EPO (40% loading)47extrudates (Milling time 10 min at 6000 rpm).3.2 X-ray diffraction patterns of pure IBU, physical IBU/EPO mixture and48extruded IBU/EPO granules, respectively.3.3 DSC thermograms of pure IBU, physical IBU/EPO mixture and49extruded IBU/EPO granules, respectively.3.4 Schematic diagram of ODTs disintegration times at various compaction53forces with a) 2%, b) 5%, c) 10% and d) 20% superdisintegrants.xix | P a g e
3.5 Schematic diagram of ODTs hardness at various compaction forces with55a) 2%, b) 5%, c) 10% and d) 20% superdisintegrants.3.6 Schematic diagram of ODTs friability at various compaction forces with56a) 2%, b) 5%, c) 10% and d) 20% superdisintegrants.3.7 Schematic diagram of ODTs disintegration times at various compaction57forces with supedisintegrants at their optimal levels.3.8 Release profiles of ODTs with IBU/EPO extruded granules of, ) 25%,59() 40% drug loading and ) Nurofen®.CHAPTER 44.1a MTDSC thermograms of pure PMOL (inset) and Eudragit EPO,70Kollidon VA644.1b MTDSC thermograms of PMOL/EPO extrudates at different PMOL70loadings.4.1c MTDSC thermograms of PMOL/VA64 extrudates at different PMOL72loadings.4.2a Powder XRPD patterns of PMOL/EPO solid dispersion (SD) and73physical mixtures (PM) systems: (a) PMOL (b) PMOL/EPO 60% PM(c) PMOL/EPO 60% Ext. (d) PMOL/EPO 50% PM (e) PMOL/EPO50% Ext.50% (f) PMOL/EPO 40% PM (g) PMOL/EPO 40% Ext.4.2b Powder XRPD patterns of PMOL pure (DIF), PMOL/VA64 extruded74(ext) and physical mixtures (PM) samples: (a) PMOL/VA64 50% PM(b) PMOL/VA64 50% ext (c) PMOL/VA64 40% PM (d) PMOL/VA6440% Ext (e) PMOL/VA64 30% PM and (f) PMOL/VA64 30% Ext.xx | P a g e
Page 3 and 4: DECLARATION“I certify that this w
Page 6 and 7: taste masking effect of the process
Page 8 and 9: CHAPTER 2: DISSOLUTION ENHANCEMENT
Page 10 and 11: 3.2 Powder and ODT characterization
Page 12 and 13: 3.7 In vitro drug release profiles
Page 15: 3.1 Solubility parameters and extru
Page 18 and 19: polymers.7.2 DSC findings of all AP
Page 22 and 23: 4.3 Schematic representation of the
Page 24 and 25: 55 exrudates (b) DPD/L100-55 PM (c)
Page 26 and 27: 8.5d A plot of the logarithm of HCS
Page 28 and 29: L100Eudragit L100L100-55 Eudragit L
Page 30 and 31: Maniruzzaman M, Rai D, Boateng JS.
Page 32 and 33: Maniruzzaman M, Boateng JS, Bonnefi
Page 34 and 35: CHAPTER 1: INTRODUCTION1.0 Backgrou
Page 36 and 37: Table 1.1: HME and other convention
Page 38 and 39: homogenize but also compress the ex
Page 40 and 41: properties of polymers and excipien
Page 42 and 43: particles‘ wettability [46] . A v
Page 44 and 45: Table 1.2: Different hot-melt extru
Page 46 and 47: 1.8 Aims and objectivesThe purpose
Page 48 and 49: 29. Zheng X, Yang R, Tang X and Zhe
Page 50 and 51: 56. International Conference on Har
Page 52 and 53: CHAPTER 2: DISSOLUTION ENHANCEMENT
Page 54 and 55: Fdid ,Vi F2pip , p( Ehi/ ViVi )i =
Page 56 and 57: used. Each sample was scanned from
Page 58 and 59: Furthermore, by means of thermodyna
Page 60 and 61: 3.2 Particle size morphology and pa
Page 62 and 63: Fig. 2.4a: Diffractograms of INM fo
Page 64 and 65: However, the DSC thermograms of the
Page 66 and 67: Fig. 2.5b: DSC thermograms of INM a
Page 68 and 69: Fig. 2.5e: DSC thermograms of FMT a
Page 70 and 71:
Nevertheless, more than 80% FMT was
Page 72 and 73:
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
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7 Astree sensors Taste masking effi
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The in vitro e-tongue evaluation wa
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3. K. Woertz, C. Tissen, P. Kleineb
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25. B.C. Hancock, P. York, R.C. Row
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CHAPTER 5: AN IN VIVO AND IN VITRO
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(dispersion forces and polarization
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Table 5.1: Sample preparation for t
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Table 5.2: Solubility parameters ca
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Physical mixtures (PM) and extruded
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Fig. 5.2c: Thermograms of CTZ and V
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masking effect for active concentra
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Fig. 5.5b: Distance and discriminat
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Table 5.4: Mean standard deviation
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Fig. 5.6b: Release profiles of VRP
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17. Woertz K,Tissen C, Kleinebudde
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scale or lower. XPS is more accurat
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patterns were identified after ener
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3.3 Differential scanning calorimet
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Fig. 6.3a: Diffractograms of PRP fo
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good agreement with the anticipated
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Since L100 contained higher proport
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at ~533.01 eV is the combination of
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Finally, the XPS analysis confirmed
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Fig. 6.6b: 1 H NMR spectra of all P
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6) Bonferoni, M.C.; Rossi, S.; Ferr
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26) Vandencasteele, N.; Reniers, F.
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Gibbs free energy change before and
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2.5 Hot-melt extrusion (HME) proces
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2.11 X-ray photoelectron spectrosco
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Table 7.2: DSC findings of all APIs
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3.4 In vivo and in vitro taste mask
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Fig. 7.3c: Normalised DI (%) of all
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Table 7.4: Binding energy calculati
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PRP/ polymers extruded in compariso
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atom as NH + 4 . This observed N 1s
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8.0 ConclusionsThe presence of inte
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20. Davies MC, Wilding IR, Short RD
Page 184 and 185:
CHAPTER 8: SUSTAINED RELEASE HYDROC
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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
Page 202 and 203:
14. Lam PL, Lee KKH,Wong RSM, Cheng
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Furthermore, HME has successfully b
Page 206 and 207:
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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