Multiparticulate tablets with uncoated and coated {_K63-carrageenan [kappa-carrageenan] pellets [Elektronische Ressource] / vorgelegt von Dima Ghanam

Beckers

Sujets

• Gesundheit

Informations

• Publié par: heinrich-heine-universitat_dusseldorf
• Publié le: 01 janvier 2011
• Nombre de lectures: 17
• Langue: English
• Poids de l'ouvrage: 4 Mo

Extrait

Multiparticulate tablets with uncoated and
coated κ-carrageenan pellets
Inaugural-Dissertation
zur Erlangung des Doktorgrades
der Mathematisch-Naturwissenschaftlichen Fakultät
der Heinrich-Heine-Universität Düsseldorf
vorgelegt von
Dima Ghanam
aus Damaskus
Düsseldorf, Dezember 2010 aus dem Institut für pharmazeutische Technologie und Biopharmazie
der Heinrich-Heine-Universität Düsseldorf
Gedruckt mit der Genehmigung der
Mathematisch-Naturwissenschaftlichen Fakultät der
Heinrich-Heine-Universität Düsseldorf
Referent: Prof. Dr. Peter Kleinebudde
Koreferent: Prof. Dr. Jörg Breitkreuz


Tag der mündlichen Prüfung: 21.01.2011

II
Table of contents
Table of contents
1 Introduction ................................................................................................................ 1
1.1 Pellets as a multiparticulate dosage form .................................................................. 1
1.2 Production of pellets ................................................................................................... 2
1.2.1 Overview ............................................................................................................. 2
1.2.2 Extrusion/spheronization .................................................................................... 2
1.2.2.1 Principle, advantages and challenges ........................................................ 2
1.2.2.2 Equipments available for extrusion ............................................................. 3
1.2.2.3 κ-carrageenan as a pelletization aid ........................................................... 7
1.3 Compression of pellets ............................................................................................... 9
1.3.1 Advantages of multiparticulate tablets ................................................................ 9
1.3.2 Challenges involved in the compression of pellets ............................................ 9
1.3.3 Compression of uncoated pellets ..................................................................... 10
1.3.4 ion of cts ......................................................................... 13
1.3.4.1 Compression of enteric coated pellets...................................................... 13
1.3.4.2 ion of pellets with sustained release coating ............................ 15
1.3.5 Compression of pellets in an embedding filler.................................................. 16
1.3.6 High density silicified microcrystalline cellulose SMCC HD 90 ........................ 18
2 Aim of the work .......................................................................................................... 20
3 Results and discussion ............................................................................................. 21
3.1 Production of pellets using the flat die press 14-175 ............................................... 21
3.1.1 Objective ........................................................................................................... 21
3.1.2 The flat die press 14-175 .................................................................................. 21
3.1.2.1 Description ................................................................................................ 21
3.1.2.2 Working principle ...................................................................................... 23
3.1.3 Model and choice of formulations ..................................................................... 25
3.1.4 Amount of water needed for extrusion/spheronization ..................................... 25
3.1.5 Characterization of the prepared pellet formulations ....................................... 26
3.1.5.1 Yield of the pelletization process .............................................................. 26
3.1.5.2 Size and size distribution .......................................................................... 26
3.1.5.3 Shape ........................................................................................................ 28
3.1.5.4 Mechanical resistance .............................................................................. 30
III
Table of contents
3.1.5.5 Drug release ............................................................................................. 31
3.1.6 Summary of results and outlook ....................................................................... 33
3.2 Compression behavior of κ-carrageenan pellets ..................................................... 35
3.2.1 Objective, Model and choice of formulations .................................................... 35
3.2.2 Properties of the uncompressed pellets ........................................................... 37
3.2.3 Scanning electron microscopy ......................................................................... 37
3.2.4 Image analysis .................................................................................................. 40
3.2.5 Fracture force and porosity measurements ...................................................... 42
3.2.6 Effect of process parameters............................................................................ 48
3.2.6.1 Size and shape of compressed pellets ..................................................... 48
3.2.6.2 Properties of tablets .................................................................................. 50
3.2.7 Summary of results ........................................................................................... 51
3.3 SMCC HD 90 as embedding powder ....................................................................... 53
3.3.1 Objective and model ......................................................................................... 53
3.3.2 Characterization of tablets ................................................................................ 54
3.3.2.1 Tensile strength ........................................................................................ 54
3.3.2.2 Elastic recovery ......................................................................................... 56
3.3.2.3 Friability ..................................................................................................... 56
3.3.2.4 Disintegration time .................................................................................... 56
3.3.2.5 Uniformity of content ................................................................................. 58
3.3.3 Cushioning effect .............................................................................................. 59
3.3.4 Summary of results ........................................................................................... 60
3.4 Compression of enteric coated κ-carrageenan pellets ............................................. 61
3.4.1 Model and choice of polymer and formulations ................................................ 61
3.4.2 Characterization of the uncoated pellets .......................................................... 62
3.4.2.1 Size and shape ......................................................................................... 62
3.4.2.2 Disintegration time .................................................................................... 62
3.4.3 Drug release from the coated pellets ............................................................... 63
3.4.4 Characterization of the tablets .......................................................................... 64
3.4.4.1 Mechanical resistance .............................................................................. 64
3.4.4.2 Disintegration Time ................................................................................... 65
3.4.4.3 Drug release ............................................................................................. 65
3.4.4.3.1 Effect of coating level ........................................................................ 65
3.4.4.3.2 Effect of compression pressure ......................................................... 68
3.4.4.3.3 Effect of pellet core ............................................................................ 68
3.4.4.3.4 Effect of punch configurations ........................................................... 71
3.4.5 Summary of results ........................................................................................... 73
3.5 Compression of κ-carrageenan pellets with sustained release coating ................... 74
3.5.1 Objective and choice of polymer and formulations .......................................... 74
3.5.2 Characterization of the uncoated pellets .......................................................... 75
IV
Table of contents
3.5.2.1 Size and shape ......................................................................................... 75
3.5.2.2 Disintegration time .................................................................................... 76
3.5.2.3 Drug release ............................................................................................. 76
3.5.3 Drug release from the coated pellets ............................................................... 77
3.5.4 Characterization of tablets ................................................................................ 79
3.5.4.1 Crushing force ..