Enteric coated mucoadhesive micropellets in rotary agglomeration process for wet spheronization [Elektronische Ressource] / Marcus Hans Knöll

Marcus Horton

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• Gesundheit

Informations

• Publié par: johannes_gutenberg-universitat_mainz
• Publié le: 01 janvier 2007
• Nombre de lectures: 63
• Langue: English
• Poids de l'ouvrage: 27 Mo

Extrait

ENTERIC COATED MUCOADHESIVE
MICROPELLETS IN ROTARY
AGGLOMERATION PROCESS FOR WET
SPHERONIZATION


Dissertation zur Erlangung des Grades
„Doktor der Naturwissenschaften“



am Fachbereich Chemie und Pharmazie und Geowissenschaften
der Johannes Gutenberg-Universität
Mainz




Marcus Hans Knöll
geb. in Frankfurt / Main




Mainz 2006














D 77




































Tag der mündlichen Prüfung: 8. Dezember 2006













To


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II

ACKNOWLEDGEMENTS
III

IV


TABLE OF CONTENTS
DEDICATION ……………………………………………………………………………………………………..I
ACKNOWLEDGEMENTS...................................................................................................................... III
TABLE OF CONTENTS..........................................................................................................................V
LIST OF TABLES ..................................................................................................................................IX
LIST OF FIGURES.................................................................................................................................XI
ABBREVIATIONS.................................................................................................................................XV
INTRODUCTION..................................................................................................................................... 1
AIMS ....................................................................................................................................... 1
CHAPTER I BACKGROUND............................................................................................................. 3
I.1. Basis for Drug Delivery to the Gastrointestinal Tract............................................................... 3
I.1.1. Anatomy and Physiology of the Gastrointestinal Tract........................................................ 3
I.1.2. Secretions of the Mucosa of the Gastrointestinal Tract....................................................... 5
I.2. Transit of Dosage Forms.......................................................................................................... 6
I.2.1. Oesophageal Transit............................................................................................................ 6
I.2.2. Gastric Emptying of Liquid Dosage Forms .......................................................................... 6
I.2.3. Gastric Emptying of Non-Digestible Solids (Solid Dosage Forms and Drug Particles)....... 7
I.2.4. Small Intestinal Transit......................................................................................................... 7
I.2.5. Large Intestinal Transit ........................................................................................................ 8
I.2.6. Prolongation of Gastrointestinal Transit Time...................................................................... 8
I.3. Mucoadhesion.......................................................................................................................... 9
I.3.1. Mechanisms of Mucoadhesion .......................................................................................... 10
I.3.2. Mucoadhesive Polymer Types........................................................................................... 11
I.3.3. Challenges to the Concept of Mucoadhesion .................................................................... 15
I.4. Mucoadhesive Polymers........................................................................................................ 16
I.4.1. Natural Polymers................................................................................................................ 16
I.4.2. Semi-Synthetic Polymers................................................................................................... 19
I.4.3. Synthetic Polymers ............................................................................................................ 21
I.5. Granulation Processes........................................................................................................... 28
I.5.1. Binding Forces of Granules ............................................................................................... 28
I.5.2. Growth Mechanisms of the Particles ................................................................................. 29
I.5.3. Fluidized Bed Technology.................................................................................................. 30
I.5.4. Rotary Processor ............................................................................................................... 34
CHAPTER II MATERIALS AND EQUIPMENT................................................................................. 40
II.1. Materials ........................................................................................................................... 40
II.2. Equipment / Software............................................................................................................. 41
CHAPTER III METHODS................................................................................................................... 43
III.1. Manufacturing of Pellets Using the GPCG1 Rotary Processor.............................................. 43
III.1.1. Na-CMC Micropellets Production....................................................................................... 43
III.1.2. Na-Alginate Micropellets Production.................................................................................. 48
III.1.3. Chitosan Micropellets Production ...................................................................................... 50
®
III.1.4. Carbopol Micropellets Production .................................................................................... 53
III.1.5. Noveon Micropellets Production ........................................................................................ 53
III.2. Characterization of Micropellets............................................................................................. 54
III.2.1. Particle Size Distribution .................................................................................................... 54
V

III.2.2. Tapped Density.................................................................................................................. 55
III.2.3. Friability Testing................................................................................................................. 55
III.2.4. Water Content at the End of the Spraying Period.............................................................. 55
III.2.5. Drying Kinetics of the Micropellets..................................................................................... 55
III.2.6. Scanning Electron Microscopy (SEM) ............................................................................... 55
III.2.7. True Density....................................................................................................................... 55
III.2.8. Estimation of the Surface Area with the Modified Blaine Method...................................... 56
III.2.9. NMR for Acetic Acid Content in the Chitosan Micropellets................................................ 57
III.2.10. Content Uniformity of Theophyllin within Micropellets by HPLC........................................ 57
III.2.11. Statistical Analysis ............................................................................................................. 58
III.3. Enteric Coating of the Micropellets ........................................................................................ 58
III.3.1. Terminology ....................................................................................................................... 58
III.3.2. Formulation of the Spraying Suspension........................................................................... 58
III.3.3. Enteric Coating using the Mini-Glatt .................................................................................. 60
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III.3.4. Enteric Coating using the Hüttlin Mycrolab ...................................................................... 63
III.4. Dissolution Testing................................................................................................................. 66
III.4.1. Screening of Dissolution Methods for Mucoadhesive Micropellets ................................... 66
III.4.2. Dissolution of the Developed and Manufactured Micropellets using App. 2 and App. 4... 69
III.4.3. Dynamic Hydration Properties of Excipients for Mucoadhesive Micropellets.................... 71
III.4.4. Electron Dispersive X-Ray Method for Proving the Separation of an Enteric Coating Layer
from a Mucoadhesive Matrix Layer.................................................................................... 73 <