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

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homogenize but also compress the extrudate to ensure the molten material reaches the finalsection of the barrel (metering zone) in a form appropriate for processing. Finally the finalsection which is known as the metering zone stabilizes the effervescent flow of the matrix andensures the extruded product has a uniform thickness, shape and size. A constant and steadyuniform screw flight depth and pitch helps maintain continuous high pressure ensuring a uniformdelivery rate of extrudates through the extrusion die and hence a uniform extruded product.Fig. 1.3: Screw geometry (extrusion) [9] .In addition to the above mentioned systems, downstream auxiliary equipment forcooling, cutting, collecting the finished product is also typically employed. Mass flow feeders toaccurately meter materials into the feed hopper, pelletizers, spheronizer, roller/calendaringdevice in order to produce continuous films and process analytical technology such as near infrared(NIR) and Raman, ultra sound, DSC systems are also options. Throughout the wholeprocess, the temperature in all zones are normally controlled by electrical heating bands andmonitored by thermocouples.The single screw extrusion system is simple and offers lots of advantages but still doesnot acquire the mixing capability of a twin-screw machine and therefore is not the preferredapproach for the production of most pharmaceutical formulations. Moreover, a twin-screwextruder offers much greater versatility (process manipulation and optimisation) inaccommodating a wider range of pharmaceutical formulations making this set-up much moreconstructive. The rotation of the screws inside the extruder barrel may either be co-rotating5 | P a g e
(same direction) or counter-rotating (opposite direction), both directions being equivalent from aprocessing perspective (Fig. 1.4). A greater degree of conveying and much shorter residencetimes are achievable with an intermeshing set-up. Furthermore, the use of reverse-conveying andforward-conveying elements, kneading blocks and other intricate designs as a means ofimproving or controlling the level of mixing required can help the configuration of the screwsthemselves to be varied [16] .Fig. 1.4: A twin screw extruder and screws [9] .1.3 Advantages and disadvantages of HMEAdvantagesHME offers several advantages over conventionally available pharmaceutical processingtechniques via appopriate selections of polymeric (thermoplastic) carrers as discussed in Table1.1, including: (a) increased solubility and bioavailability of water insoluble compounds, (b)solvent free non ambient process, (c) economical process with reduced production time, fewerprocessing steps, and a continuous operation, (d) capabilities of sustained, modified and targetedrelease, (e) better content uniformity in extrudates, (f) no requirements for the compactibility ofactive ingredients, (g) uniform dispersion of fine particles, (h) good stability at changing pH andmoisture levels and safe application in humans, (i) reduced number of unit operations andproduction of a wide range of performance dosage forms, and (j) a range of screw geometries [17,18, 19, 20, 21] .DisadvantagesHowever, HME has some disadvantages as well. The main drawbacks of HME include:thermal process (drug/polymer stability), use of a limited number of polymers, high flow6 | 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 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
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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
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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
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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
Page 136 and 137:
Fig. 5.6b: Release profiles of VRP
Page 138 and 139:
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
Page 144 and 145:
3.3 Differential scanning calorimet
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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
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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.
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Gibbs free energy change before and
Page 164 and 165:
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
Page 170 and 171:
3.4 In vivo and in vitro taste mask
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Fig. 7.3c: Normalised DI (%) of all
Page 174 and 175:
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
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
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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
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N = 55000/ 219.2 = 250.912Density:
Page 218 and 219:
(4) Eudragit L100, N = (125000/202
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