6. Caron V, Tajber L, Corrigan OI, Healy AM. A comparison <strong>of</strong> spray drying and milling in<strong>the</strong> production <strong>of</strong> amorphous dispersions <strong>of</strong> sulfathiazole/polyvinylpyrrolidone andsulfadimidine/polyvinylpyrrolidone. Mol Pharm 2011; 8(2):532-42.7. Wu K, Li J, Wang W, Winstead DA. Formation and characterization <strong>of</strong> solid dispersions<strong>of</strong> piroxicam and polyvinylpyrrolidone using spray drying and precipitation withcompressed antisolvent. J Pharm Sci. 2009; 98(7):2422-31.8. Gong K, Viboonkiat R, Rehman IU, Buckton G, Darr JA. Formation and characterization<strong>of</strong> porous indomethacin- PVP coprecipitates prepared using solvent-free supercriticalfluid processing. J Pharm Sci 2005; 94(12): 2583–2590.9. Repka MA, Battu SK, Upadhye SB, Thumma S, Crowley MM, Zhang F, Martin C, et alPharmaceutical applications <strong>of</strong> <strong>hot</strong>-<strong>melt</strong> <strong>extrusion</strong>: Part II. Drug Dev Ind Pharm 2007;33(10): 1043-1057.10. Qi S, Gryczke A, Belton P, Craig DQM. Characterisation <strong>of</strong> solid dispersions <strong>of</strong>paracetamol and EUDRAGIT® E prepared by <strong>hot</strong>-<strong>melt</strong> <strong>extrusion</strong> using <strong>the</strong>rmal,micro<strong>the</strong>rmal and spectroscopic analysis. Int J Pharm 2008; 354: 158–167.11. Forster A, Hempenstall J, Rades T. Characterization <strong>of</strong> gl<strong>as</strong>s solutions <strong>of</strong> poorly watersolubledrugs produced by <strong>melt</strong> <strong>extrusion</strong> with hydrophilic amorphous polymers. JPharm Pharmacol 2001a; 53(3): 303–315.12. Forster A, Hempenstall J, Tucker I, Rades T. Selection <strong>of</strong> excipients <strong>for</strong> <strong>melt</strong> <strong>extrusion</strong>with two poorly water-soluble drugs by solubility parameter calculation and <strong>the</strong>rmalanalysis. Int J Pharm 2001b; 226(1–2): 147–161.13. Rambali B, Verreck G, Baert L, M<strong>as</strong>sart DL. Itraconazole <strong>for</strong>mulation studies <strong>of</strong> <strong>the</strong><strong>melt</strong>-<strong>extrusion</strong> process with mixture design. Drug Dev Pharm 2003; 29(6): 641–652.14. Six K, Daems T, de Hoon J, Van Hecken A, Depre M, Bouche MP, Prinsen P, VerreckG, Peeters J, Brewster ME, Van den Mooter G. Clinical study <strong>of</strong> solid dispersions <strong>of</strong>itraconazole prepared by <strong>hot</strong>-stage <strong>extrusion</strong>. Eur J Pharm Sci 2005; 24(2–3): 179–186.15. Wang L, Cui FD, Hay<strong>as</strong>e T, Sunada H. Preparation and evaluation <strong>of</strong> solid dispersion <strong>for</strong>nitrendipine-carbopol and nitrendipine-HPMCP systems using a twin screw extruder.Chem Pharm Bull (Tokyo) 2005; 53(10): 1240–1245.16. Jaimini M, Rana AC, Tanwar YS. Formulation and evaluation <strong>of</strong> famotidine floatingtablets. Curr Drug Deliv 2007; 4(1); 51-55.17. Wenning LA, Murphy MG, James LP, Blumer JL, Marshall JD, Baier J, Scheimann, AO,et al. Pharmacokinetics <strong>of</strong> famotidine in infants. Clin Pharmaco 2005;44(4):395-406.39 | P a g e
18. Amidon GL, Lunnern<strong>as</strong> H, Shah VP, and Crison JR. A <strong>the</strong>oretical b<strong>as</strong>is <strong>for</strong> abiopharmaceutic drug cl<strong>as</strong>sification: <strong>the</strong> correlation <strong>of</strong> in vitro drug product dissolutionand in vivo bioavailability. Pharm Res1995; 12:413–420.19. El-Badry M, Fetih G, Fathy M. Improvement <strong>of</strong> solubility and dissolution rate <strong>of</strong>indomethacin by solid dispersions in Gelucire 50/13 and PEG4000. Saudi Pharm J 2009;17: 217-225.20. De<strong>as</strong>y PB, Law MFL. Use <strong>of</strong> <strong>extrusion</strong>-spheronization to develop an improved oraldosage <strong>for</strong>m <strong>of</strong> Indomethacin. Int J Pharm 1997; 148: 201-209.21. Mady FM, Abou-Taleb AE, Khaled KA, Yam<strong>as</strong>aki K, Iohara D, Taguchi K, Anraku, M,et al. Evaluation <strong>of</strong> carboxymethyl-beta-cyclodextrin with acid function: improvement <strong>of</strong>chemical stability, oral bioavailability and bitter t<strong>as</strong>te <strong>of</strong> famotidine. Int J Pharm 2010;397(1-2): 1-8.22. Hansen CM. The universality <strong>of</strong> <strong>the</strong> solubility parameter. Ind Eng Chem Res Dev 1969;8: 2-11.23. H<strong>of</strong>tyzer PJ, Krevelen DWV. Properties <strong>of</strong> polymers. Amsterdam: Elsevier, 1976:24. Bagley EB, Nelson TP & Scigliano JM. Three-dimensional solubility parameters and<strong>the</strong>ir relationship to internal pressure me<strong>as</strong>urements in polar and hydrogen bondingsolvents. J Paint Technol 1971; 43: 35-42.25. Zheng X, Yang R, Tang X and Zheng L. Part I: Characterization <strong>of</strong> Solid Dispersions <strong>of</strong>Nimodipine Prepared by Hot-<strong>melt</strong> Extrusion. Drug Dev Ind Pharm 2007; 33:791–802.26. Greenhalgh DJ, Peter W, York TP, Solubility parameters <strong>as</strong> predictors <strong>of</strong> miscibility insolid dispersions. J Pharm Sci 1999; 88 (11): 1182–1190.27. Hancock BC, York P, Rowe RC. The use <strong>of</strong> solubility parameters in pharmaceuticaldosage <strong>for</strong>m design. Int J Pharm 1997; 148(1): 1–21.28. Albers, J. Hot-<strong>melt</strong> Extrusion with Poorly Soluble Drugs. Heinrich-Heine- UniversitatDusseldorf, Germany 2008.29. Forster A, Hempenstall J, Tucker I, Rades T. The potential <strong>of</strong> small-scale fusionexperiments and Gordon–Taylor equation to predict <strong>the</strong> suitability <strong>of</strong> drug/polymerblends <strong>for</strong> <strong>melt</strong> <strong>extrusion</strong>. Drug Dev Ind Pharm 2001c; 27:549– 560.30. Guidance <strong>for</strong> Industry. Dissolution Testing <strong>of</strong> Immediate Rele<strong>as</strong>e Solid Oral DosageForms U.S. Department <strong>of</strong> Health and Human Services Food and Drug Administration,Center <strong>for</strong> Drug Evaluation and Research (CDER). 1997.40 | 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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- 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
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- Page 46 and 47: 1.8 Aims and objectivesThe purpose
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- Page 56 and 57: used. Each sample was scanned from
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- 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
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- Page 96 and 97: 30. L. Saerens, L. Dierickx, B. Len
- Page 98 and 99: leading to significant variations w
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- Page 102 and 103: v2d 2p(4.1)Table 4.1: Calculated so
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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
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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
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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