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

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3.4 In vivo and in vitro taste masking evaluationThe masking efficiency of the developed granules was evaluated in vivo with theassistance of six healthy human volunteers (age 18 – 25). The statistical data collected fromthe in vivo study for the pure active substances and the extruded formulations are depicted inFig. 3a. The data analysis showed significant suppression of the bitter taste for both APIs &influence of the polymeric carriers and importance of drug loading in the final formulation.Both polymers showed effective taste masking capacity with descending order L100>EZE.Furthermore, the HME formulations presented excellent masking effect for activeconcentrations (10%) of both APIs. In Fig. 7.3a sensory data obtained from six volunteersinterestingly showed the taste masking efficiency of L100 significantly better than EZE forboth of the APIs used. This could be attributed to the pH dependant dissolution properties ofEZE (pH ≥ 6) compared to that of L100 (pH ≥ 6.5) as the saliva represents a pHapproximately 6.0 in healthy individuals. However, the sensory scores for both of the activeAPIs in different formulations are within the range (below 2) which has been demonstrated asoptimum by in vitro evaluations.Fig. 7.3a: Sensory scores of all formulations by panellist (n = 6).The in vitro masking effect of the extruded formulations in artificial salive wasevaluated by using the INSENT TS-5000Z e–tongue and the interpretation of theexperimental findings is discussed below. The distances percentage (%) between activesubtances and formulation solutions were estimated in four phases of time distances (0.5 min,1 min, 10 min and 30 min) as they are indicative of taste masking power of the extruded137 | P a g e
formulations. In addition, the Discrimination Index (DI in %) was determined for eachsolution.Fig. 7.3b: Normalised DI (%) of all drug/L100 formulations in four different time scale.This indicator takes into account the average difference between the pairs to compareeach other as well as the discrimination index (DI) of each sample. The closer the DI valuesto 0%, the longer the distance between groups and the higher the discrimination (highmasking effects). The DI will help then to assess the significance of difference between thegroups. The results are presented in the following sections for each drug in (Fig. 7.3b andFig. 7.3c).In Fig. 7.3b the bitter taste suppression of DPD in the active formulation with L100 isquite significant even after 30 min as the DI index (%) is only about 2% (very close to 0%-means no taste). Similarly, PRP/L100 extruded formulation did not show that much closertaste suppression compared to the L100 system but still about 60% DI has been determinedby the BT0 sensor thus indicating taste masking.138 | 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
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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
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 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 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
Page 210 and 211: 8.2 s 6.2 s 3.8 s 1.8 s 200 msS
Page 212 and 213: 12.2 s 9.0 s 6.2 s 3.8 s 1.8 s
Page 214 and 215: Supplementary table 1: Solubility p
Page 216 and 217: N = 55000/ 219.2 = 250.912Density:
Page 218 and 219: (4) Eudragit L100, N = (125000/202
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