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

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3.3 Differential scanning calorimetry (DSC)DSC was employed in order to analyse the solid state of the processed drug/polymersbinary mixtures (PM) and drug/polymer extrudates (EXT). The DSC thermograms of PRPand DPD in Fig. 6.2a showed an endothermic peak corresponding to melting points at166.65 o C (H= -126.25 J/g) and 170.83 o C (H= -124.59 J/g) respectively. The bulkpolymers showed Tgs at 83.97 o C and 164.83 o C corresponding to L100-55 and L100respectively (Fig. 6.2a).Fig. 6.2a: DSC thermograms of pure drugs and pure polymers.The binary physical blends of DPD/L100 and DPD/L100-55 in Fig. 6.2b exhibitedDPD endothermic peaks shifted at slightly lower temperatures of 139.19 o C (H= -15.14 J/g),153.62 o C (H=16.16 J/g), respectively, indicating drug/polymer interaction to a smallextent. The same shift at lower temperatures was observed for the Tgs of the polymers at114.46 o C for L100 and 71.98 o C for L100-55.Furthermore, the extruded DPD/L100 (and L100-55) complexes exhibited single glasstransition peaks at 62.11 and 76.56 o C, respectively, which denotes the presence ofdrug/polymers miscibility and formation of solid dispersions. Single Tg also indicates thepresence of the APIs in amorphous forms [21] . When the two components are miscible the Tgof the extruded sample lies between the Tgs of the individual components (DPD has a Tgat14.80 o C) according to the Gordon – Taylor equation [19] . Similarly, PRP/polymers exhibitedsingle Tg peaks at of 65.70 o C (L100) and 54.52 o C (L100-55) attributed to the presence ofPRP in molecularly dispersed state within both polymer matrices (Supp. Fig. 1). The Tg of111 | P a g e
PRP was determined at 34.74 o C. Overall, DSC analysis confirmed the creation of moleculardispersions for all extruded formulations.Fig. 6.2b: DSC thermograms of DPD/L100 (PM), DPD/L100 (EXT), DPD/L100-55 (PM)and DPD/L100-55 (EXT).3.4 X-ray powder diffraction (XRPD)To examine PRP and DPD crystalline state diffractograms of pure drugs, the drug –polymer extrudates and their binary physical mixtures were recorded by X–ray powderdiffraction analysis. As can be seen from Fig. 5.3, the diffractograms of pure PRP and DPDpresented distinct peaks at 8.38 o , 9.71 o , 12.51 o , 16.72 o , 19.49 o , 21.26 o , 22.06 o , 23.59 o , 25.07 o ,27.07 o -39.07 o 2 and 10.41 o , 12.39 o , 18.61 o , 20.34 o , 22.03 o , 24.87 o , 26.55 o , 31.45 o 2,respectively. As shown in Fig. 6.3 the PM of all PRP formulations presented identical peaksat lower intensities suggesting that both drugs retained their crystallinity at loads of 10%. Incontrast no distinct intensity peaks were observed in the diffractograms of the extrudedformulations. The absence of PRP and DPD intensity peaks indicates the formation of a soliddispersion where the drugs are present in amorphous [22] state or molecularly dispersed intothe polymer matrix.112 | 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
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 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 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
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
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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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