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

More documents

Recommendations

Info

Fig. 4.2a: Powder XRPD patterns of PMOL/EPO solid dispersion (SD) and physicalmixtures (PM) systems: (a) PMOL pure (b) PMOL/EPO 60% PM (c) PMOL/EPO 60% Ext.(d) PMOL/EPO 50% PM (e) PMOL/EPO 50% Ext.50% (f) PMOL/EPO 40% PM (g)PMOL/EPO 40% Ext.Crystalline PMOL has distinct crystalline peaks at 2 angles of 12.11, 13.82, 15.52,18.20, 20.42, 23.51, 24.39 and 26.59° and a series of smaller peaks at different 2 anglesranging from 26.78-38.45°. The diffraction patterns of the physical mixtures of drug andpolymers in three different ratios presented identical crystalline peaks to those of pure PMOLbut at a lower intensity. The XRD patterns of extruded formulations showed increasedamorphous trends compared to the pure PMOL due to the dispersion of the drug into thepolymer matrix. Furthermore the diffraction patterns of all the PMOL–EPO extrudatesconfirmed the presence of Form I within the polymer matrices as no new distinct crystallinepeaks at different 2 could be observed [33] . The PMOL intensity peaks supported the DSCinvestigations where crystalline drug was detected in the binary mixtures. In contrast, for thePMOL–VA64 extrudates no distinct peaks were observed suggesting the presence ofamorphous PMOL as shown in Fig. 4.2b. The absence of crystalline PMOL was detected forall drug loadings even at 50% PMOL. The combined DSC and X–ray characterizationstudies revealed different PMOL crystalline states mainly depending on the polymeric carrierand its miscibility with the active substance.73 | P a g e
Fig. 4.2b: Powder XRPD patterns of PMOL pure (DIF), PMOL/VA64 extruded (ext) andphysical mixtures (PM) samples: (a) PMOL/VA64 50% PM (b) PMOL/VA64 50% ext (c)PMOL/VA64 40% PM (d) PMOL/VA64 40% Ext (e) PMOL/VA64 30% PM and (f)PMOL/VA64 30% Ext.3.3. 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 in vivo statistical data collectedfor the pure active substance, bulk polymers and the extruded formulations are summarized inTable 3. The data analysis showed significant suppression of the bitter taste for PMOL andstrong influence of the polymeric carriers indicating the importance of drug loading in thefinal formulation.Both polymers showed improved taste masking capacity for certain formulations withdescending order VA64>EPO. The PMOL/EPO extrudates presented masking effect foractive concentrations up to 50% with panellists‘ scores showing slight bitterness. In Fig. 4.3it can be seen that PMOL/EPO extrudates showed better taste suppression at 40% loadingwhile at 60% no masking effect was observed. The PMOL/VA64 extrudates demonstratedsimilar masking effect where for PMOL loadings from 40 – 50% the recorded scoressuggested slight bitterness. The PMOL/VA64 (30%) extrudates showed improved maskingeffect with panellists‘ scores indicating threshold values.74 | 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 20 and 21:
2.4b Diffractograms of FMT formulat
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,
Page 74 and 75: CHAPTER 3: DEVELOPMENT AND EVALUATI
Page 76 and 77: 2.2 Hot-Melt extrusionHot-melt extr
Page 78 and 79: Committee of the University of Gree
Page 80 and 81: The PM of formulation II (40% IBU)
Page 82 and 83: Fig. 3.3: DSC thermograms of pure I
Page 84 and 85: As a general rule, the powder compr
Page 86 and 87: Fig. 3.4: Schematic diagram of ODT
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
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 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 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 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
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
show all

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

Create successful ePaper yourself

Delete template?

Save as template?