EVALUATION OF NEW FILM COATING PROCESSES AND MATERIALS

Transcription

1 EVALUATION OF NEW FILM COATING PROCESSES AND MATERIALS Inaugural-Dissertation zur Erlangung der Doktorwurde im Fachbereich Biologie, Chemie, Pharmazie der Freien Universitat Berlin vorgelegt von NANTHARAT PEARNCHOB Berlin 2002

2 TABLE OF CONTENTS Page CHAPTER 1. Introduction 1 1 Single Unit Dosage Forms Tablets Protective and Insulating Coatings for Tablets Extended Release Matrix Tablets with Enteric polymers Soft Gelatin Capsules 4 2 Multiparticulates Therapeutic and Biopharmaceutical Advantages Technological Advantages Polymeric Coatings for Pellets 9 3 Shellac General Background Extraction and Production Processes Physicochemical Properties of Shellac Polymer Compatibility and Plasticization of Shellac Films Shellac for Pharmaceutical Applications 15 4 Ethylcellulose General Background Solubility Parameters of Ethylcellulose Ethylcellulose Solubility Diagrams Solvents for Ethylcellulose Ethylcellulose for Pharmaceutical Applications 26 5 Polymeric Coating Systems Organic Polymer Solutions Aqueous Polymer Solutions Water-Soluble Polymers Enteric Polymers Aqueous Colloidal Polymer Dispersions Latex Film Formation Theoretical Aspects 34

3 5.4 Aqueous Micronized Polymer Dispersions Dry Polymer Powders 41 6 Plasticizers for Polymeric Coatings 43 7 Research Objectives 49 CHAPTER 2. Materials and Experimental Procedures 52 1 Materials 52 2 Experimental Procedures Neutralization Studies Preparation of Polymer Solutions and Dispersions Physical-Mechanical Properties of Polymeric Films Preparation of Polymeric Films Determinations of Water Content and Weight loss Measurements of Mechanical Properties Investigation of Pellets Preparation of Drug-Loaded Pellets Coating of Pellets Thermal treatment (Curing) of Pellets Investigation of Soft Gelatin Capsules Coating of Soft Gelatin Capsules Disintegration Studies Hardness of Coated Soft Gelatin Capsules Medium Uptake of Coated Soft Gelatin Capsules Moisture Uptake of Coated Soft Gelatin Capsules Investigation of Tablets 67 ' Preparation of Tablets Coating of Tablets Evaluation of Taste Masking Ability Moisture Uptake and Drug Stability Studies Plasticizer Soaking for Ethylcellulose Powder Dissolution Studies Thermal Analysis Measurements of Minimum Polymer-Softening Temperature 72 ii

4 2.11 Particle Size Measurements Scanning Electron Microscopy Solubility Determinations of Polymers Solubility of the Organic Acids Contact Angle Measurements Liquid Penetration Experiments 74 CHAPTER 3. Results and Discussion 77 1 Pharmaceutical Applications of Shellac Investigation of Shellac as Enteric Coating Material: Ethanolic Solution Film Properties of Shellac Ethanolic Shellac-Coated Pellets Ethanolic Shellac-Coated Soft Gelatin Capsules Film Properties of Synthetic Enteric Polymers Investigation of Shellac as Enteric Coating Material: Aqueous. Solution Properties of Aqueous-Cast Shellac Films Aqueous Shellac-Coated Pellets Aqueous Shellac-Coated Soft Gelatin Capsules Improvement in the Disintegration of Shellac-Coated Soft Gelatin Capsules in Simulated Intestinal Fluids Ethanolic Shellac Coating Ill Aqueous Shellac Coating Pharmaceutical Applications of Shellac: Moisture Protective and Taste / Masking Coatings and Extended Release Matrix Tablets Moisture Protective Polymer Coatings Taste Masking Polymer Coatings Extended Release Matrix Tablets Dry Powder Coating Dry Powder Coating of Pellets with Eudragit RS for Extended Drug Release 137

5 2.2 Coating of Pellets with Micronized Ethylcellulose Particles by a Dry Powder Technique Formulation and Processing Variables of Dry Powder Coating and Comparison with Conventional Coatings: Eudragit RS, ethylcellulose, shellac, Phthalate-Free Coating Materials Extended Release Coated Dosage Forms with Ethylcellulose Containing Phthalate-Free Plasticizers Ethylcellulose and Plasticizer Compatibility Thermal Properties of Ethylcellulose Coating Formulations for Pellets Coated with Ethanolic Ethylcellulose Solution Drug Release from Ethanolic Ethylcellulose-Coated Pellets Drug Release from Aqueous Ethylcellulose-Coated Pellets 205 CHAPTER 4. Summary and Conclusions 209 CHAPTER 5. References 217 CHAPTER 6. Appendix. 242 CHAPTER 7. Publications 244 CHAPTER 8. Curriculum Vitae 247 iv