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

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ACKNOWLEDGEMENTSI would like to take the opportunity to extend my gratitude and appreciation to almighty‗ALLAH‘ who helped me numerously to make this thesis possible (Alhamdulillah). I wouldalso like to thank my parents for their continuous support and help throughout the past yearsand my lovely wife and sweet sister for being with me during the three years of my researchand giving me lots of inspiration and support.I would like to express my gratitude to my supervisors, Dr. Dionysios Douroumisand Dr Joshua S. Boateng for their guidance at each step of my progress. I am particularlyindebted to my first supervisor Dr. Dionysios Douroumis whose help, stimulating suggestionsand encouragement helped me at all times during this research. Many thanks also to ProfChowdhry for all his support and encouragement throughout my PhD study.I would also like to thank the School of Science of the University of Greenwich for giving methe opportunity to undertake this doctoral research and to use department facilities.Furthermore I would like to extend my thanks to Dr Milan Antonijevic for his kind assistanceand guidance in the DSC studies, Dr Jiayun Pang for kind support in molecular modellingand Mrs Devyani Amin for her help with the HPLC experiments. I am also grateful to Dr IanSlipper and Dr A. Mendham of the School of Science whose assistance during this project isgreatly appreciated.I would especially like to thank my parents for their moral and financial support to get me tothis level of my career. I am grateful to my fellow PhD students and friends for theirassistance and mental support during my project work. Finally, I want to take the opportunityto thank all the staff of the Drill Hall Library.iii | P a g e
Page 3: DECLARATION“I certify that this w
Page 7 and 8: CONTENTSContentsPage NoTITLE PAGE..
Page 9 and 10: CHAPTER 3: DEVELOPMENT AND EVALUATI
Page 11 and 12: 4.0 Conclusions ...................
Page 13: 3.5.2 X-ray photoelectron spectrosc
Page 17 and 18: CHAPTER 44.1 Calculated solubility
Page 19 and 20: FIGURESFigureN o N oTitle PageCHAPT
Page 21 and 22: 3.5 Schematic diagram of ODTs hardn
Page 23 and 24: materials.5.5a Signal comparison be
Page 25 and 26: 7.4a FTIR spectra of PRP extruded f
Page 27 and 28: ABBREVIATIONSAbbreviationAPICaStCL,
Page 29 and 30: PUBLICATIONSOriginal Research Artic
Page 31 and 32: Melt Extrusion. 39 th Annual meetin
Page 33 and 34: Maniruzzaman M, Chowdhry BZ, Snowde
Page 35 and 36: sustained release polymer based pel
Page 37 and 38: parameters such as screw speed, tem
Page 39 and 40: (same direction) or counter-rotatin
Page 41 and 42: 1.5 Formulation research and develo
Page 43 and 44: However, only a handful of research
Page 45 and 46: oral and transdermal applications.
Page 47 and 48: 12. Gryczke A. Melt Extrusion with
Page 49 and 50: 43. Chokshi RJ, Shah NHS, Sandhu KH
Page 51 and 52: 70. Klein CE, Chiu Y, Awni W, Zhu T
Page 53 and 54: spondylitis, tendinitis and headach
Page 55 and 56:
(%, w/w) (%, w/w)INM SOL 20 80INM S
Page 57 and 58:
2.9 HPLC analysisThe release of INM
Page 59 and 60:
immiscibility of the two components
Page 61 and 62:
Fig. 2.3: Particles size distributi
Page 63 and 64:
Fig. 2.4b: Diffractograms of FMT fo
Page 65 and 66:
Table 2.3: DSC thermal transitions
Page 67 and 68:
By comparing the Tgs at different l
Page 69 and 70:
Fig. 2.6a: Drug release profile of
Page 71 and 72:
4.0 ConclusionsIn the current chapt
Page 73 and 74:
18. Amidon GL, Lunnernas H, Shah VP
Page 75 and 76:
interactions facilitate the creatio
Page 77 and 78:
2.6 Evaluation of tabletsThe prepar
Page 79 and 80:
dodecahydrate were added into the v
Page 81 and 82:
Fig. 3.2: X-ray diffraction pattern
Page 83 and 84:
Table 3.1: Composition of ODT formu
Page 85 and 86:
disintegrants by absorbing water an
Page 87 and 88:
grades (3.5-5.5 g water/g polymer)
Page 89 and 90:
Fig. 3.6: Schematic diagram of fria
Page 91 and 92:
Table 3.3: Comparison of disintegra
Page 93 and 94:
IBU has been reported 22% after 2 h
Page 95 and 96:
18. Verhoeven, T.R.M. De Beer, E. S
Page 97 and 98:
CHAPTER 4: TASTE MASKING OF PARACET
Page 99 and 100:
2.3. Hot-melt Extrusion (HME) proce
Page 101 and 102:
multidimensional statistics on Alph
Page 103 and 104:
Fig. 4.1a: MTDSC thermograms of pur
Page 105 and 106:
VA64 showed a baseline shift at 105
Page 107 and 108:
Fig. 4.2b: Powder XRPD patterns of
Page 109 and 110:
7 Astree sensors Taste masking effi
Page 111 and 112:
7 Astree sensorsTaste masking effic
Page 113 and 114:
exhibited the same trends but slowe
Page 115 and 116:
13. A. Michalk, V.-R. Kanikanti, H.
Page 117 and 118:
37. Y. Kong, J.N. Hay, The measurem
Page 119 and 120:
HME processing conditions, drug/pol
Page 121 and 122:
otation at 15rpm. The sample was sc
Page 123 and 124:
2.10 HPLC analysisThe release of CT
Page 125 and 126:
Fig. 5.1: SEM images (magnification
Page 127 and 128:
drugs/polymers blends exhibits endo
Page 129 and 130:
As shown in Fig. 5.3a and b the PM
Page 131 and 132:
The taste map shows significant dis
Page 133 and 134:
Fig. 5.5c: Correlation of human sen
Page 135 and 136:
Fig. 5.6a: Release profiles of CTZ
Page 137 and 138:
4. Douroumis DD, Gryczke A, Schmink
Page 139 and 140:
CHAPTER 6: DRUG-POLYMER INTERMOLECU
Page 141 and 142:
of all PRP and DPD formulations was
Page 143 and 144:
parameters between each drug and po
Page 145 and 146:
PRP was determined at 34.74 o C. Ov
Page 147 and 148:
3.5 Intermolecular interactions of
Page 149 and 150:
Fig. 6.5a: XPS BE peaks of C 1s PRP
Page 151 and 152:
For the extruded DPD/L100 samples t
Page 153 and 154:
N 1s peaks from PRP/L100-55 and DPD
Page 155 and 156:
Table 6.3: 1 H NMR assignments for
Page 157 and 158:
Table 6.4: A comparison of T 1 rela
Page 159 and 160:
18) Forster, A.; Hempenstall, J.; T
Page 161 and 162:
CHAPTER 7: EVALUATION OF THE INTERR
Page 163 and 164:
2.3 Flory Huggins (F-H) theory for
Page 165 and 166:
the bitterness intensity scale from
Page 167 and 168:
Pythagorean Theorem. In this theory
Page 169 and 170:
all formulations ranging from 40 -
Page 171 and 172:
formulations. In addition, the Disc
Page 173 and 174:
Fig.7.3d. Relationship between resu
Page 175 and 176:
L100-55-DPD (b) 17.53.6 Fourier Tra
Page 177 and 178:
Fig 7.5a: XPS surveys of pure PRP,
Page 179 and 180:
Fig. 7.5d: N 1s BE peaks of DPD and
Page 181 and 182:
acetaminophen granules: comparison
Page 183 and 184:
32. Boys SF, Bernardi F. The calcul
Page 185 and 186:
testosterone and adrenal function.
Page 187 and 188:
2.7 Tablet preparation and characte
Page 189 and 190:
Where, W 0 is the initial amount of
Page 191 and 192:
HCS melting transition and 61.66 o
Page 193 and 194:
Fig. 8.3: XRD diffractograms of ext
Page 195 and 196:
Fig. 8.4: HCS release profiles in b
Page 197 and 198:
Fig. 8.5b: A plot of the HCS releas
Page 199 and 200:
Eq. (6) is a Korsmeyer-Peppas model
Page 201 and 202:
5.0 References1. Breitenbach J. Mel
Page 203 and 204:
CHAPTER 9: CONCLUSIONS AND FUTURE W
Page 205 and 206:
CHAPTER 10: SUPPLEMENTARY DATA10.1
Page 207 and 208:
Supp. Fig. 3: C 1s BE peaks for L10
Page 209 and 210:
445 ms 345 ms 265 ms 185 ms 125
Page 211 and 212:
8.5 s 5.5 s 2.5 s 1.5 s 500 msS
Page 213 and 214:
10.2 Supplementary calculationsExam
Page 215 and 216:
∑ F di = 2352, ∑ F pi = 899100,
Page 217 and 218:
= N (mw = 418 g/mol)Molecular Weigh
Page 219:
N = (320000/202= 1584.1584)Molecula
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