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

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F2 0 0.5 0 1 0 1F6 0 0.5 0 1 0 2F7 0 0.5 0 1 0 2F10 0 0.5 0 1 0 1F11 0 0.5 0 0.5 0 0.5F13 0 0.5 0 1 0 0.5F14 0 0 0 0 0 0Nurofen® 0 1 0 1 0 23.4 In vitro dissolutionThe main objectives for this study were to increase IBU‘s dissolution rate, achievesufficient taste-masking and to provide simultaneous rapid release. The amorphous IBU statewithin the EPO polymer matrix is expected to provide increased dissolution rates.Fig. 3.8: Release profiles of ODTs with IBU/EPO extruded granules of, ) 25%, ()40% drug loading and ) Nurofen®.In Fig. 3.8, it can be seen that ODTs of 25% and 40% loadings of extruded IBU/EPOprovided rapid cumulative release profiles compared to that of pure IBU. The release of pure59 | P a g e
IBU has been reported 22% after 2 hrs [34] . In addition it was observed that increased IBUloading (40% - Formulation II) provided faster release rates in contrast to the 25% loading(Formulation I). This is attributed to the increased talc amounts (50%) in Formulation I. Asmentioned earlier talc serves as an anti-tacking agent and because of its hydrophobic natureretards polymer hydration and the subsequent IBU release rate. Comparison of the extrudedformulations with the Nurofen® tablets demonstrated similar release rates for 25% loadingbut a faster rate for the 40% IBU/EPO extrudates. Application of a Kruskal-Wallis nonparametrictest (p > 0.05) to the results showed no significant difference. Nevertheless, theHME extruded formulations showed excellent release patterns that could provide fast onsetaction in future clinical trials.4.0 ConclusionsIn this chapter we have demonstrated the manufacture of robust taste-masked IBUODTs. For the purpose of the study IBU was hot-melt extruded and embedded within aEudragit EPO polymer matrix. The in vivo taste-masking evaluation showed that HMEprocessing can be used to mask efficiently the taste of bitter active substances withoutcompromising tablet palatability. The ODTs developed showed disintegration times andcrushing resistance similar to commercial Nurofen® tablets but improved tablet friability.Finally the increased IBU release rates of the developed ODTs were faster than thecommercial Nurofen® tablets.5.0 References1. W. Habibh, R. Khankarik, J. Hontz. Fast-Dissolve Drug Delivery System. Crit RevTher Drug Carrier Syst. 17 (2000) 61-72.2. D. Douroumis. Practical approaches of taste masking technologies in oral solid forms.Expert Opin Drug Deliv. 4 (2007) 417-26.3. A. Mahesh, N. Shastri, M. Sadanandam. Development of Taste Masked FastDisintegrating Films of Levocetirizine Dihydrochloride for Oral Use. Curr DrugDeliv. 7 (2010) 21 – 7.4. A. Dinge, M. Nagarsenker. Formulation and evaluation of fast dissolving films fordelivery of triclosan to the oral cavity. AAPS PharmSciTech. 9 (2008) 349-56.5. Zydis fast dissolving technology(http://www.catalent.com/documents/file/zydis_bro_v15b_Web_MedRES.pdf)60 | 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
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 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
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patterns were identified after ener
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3.3 Differential scanning calorimet
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Fig. 6.3a: Diffractograms of PRP fo
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good agreement with the anticipated
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Since L100 contained higher proport
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at ~533.01 eV is the combination of
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Finally, the XPS analysis confirmed
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Fig. 6.6b: 1 H NMR spectra of all P
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6) Bonferoni, M.C.; Rossi, S.; Ferr
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26) Vandencasteele, N.; Reniers, F.
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Gibbs free energy change before and
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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
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3.4 In vivo and in vitro taste mask
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Fig. 7.3c: Normalised DI (%) of all
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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
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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
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Fig. 8.1: SEM images of [(a), (b)]
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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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