아주대학교

목차

Chapter 1: Formulation and Characterization of Fast Dissolving Tablets Incorporating Microenvironmental pH-Modulated Solid Dispersions 1
1. Introduction 1
2. Materials and Methods 5
2.1. Materials 5
2.2. Solubility study and evaluation of suitable pharmaceutical excipients 5
2.2.1. Initial solubility 5
2.2.2. Evaluation of suitable pharmaceutical excipients by solubility study 6
2.3. Formulation and optimization of tetrabenazine solid dispersions 6
2.3.1. Formulation and optimization of binary 6
2.3.2. Formulation and optimization of ternary solid dispersion with pH modifier 7
2.4. Drug content measurements 9
2.5. In vitro Release Study 9
2.6. Physicochemical characteristics of solid dispersions 10
2.6.1. Fourier-transform infrared spectroscopy (FT-IR) 10
2.6.2. Powder X-ray diffraction (PXRD) 10
2.6.3. Differential scanning calorimetry (DSC) 10
2.6.4. Field emission scanning electron microscope (FE-SEM) images 11
2.7. In vitro permeability study 11
2.8. Flow properties of powders and granules 11
2.9. Formulation and optimization of fast-dissolving tablets 12
2.9.1. Granulation of solid dispersions 12
2.9.2. Screening of formulation and preparation of fast-dissolving tablets 13
2.10. Physicochemical properties measurements of FDTs 15
2.10.1. Weight, thickness and drug content 15
2.10.2. Hardness, friability and weight variation of FDTs 15
2.10.3. Microenvironmental pH measurement 16
2.10.4. In vitro disintegration study 16
2.11. Stability study of granules and tablets 16
2.12. HPLC analysis 17
3. Results and discussions 18
3.1. Solubility study and evaluation of suitable pharmaceutical excipients 18
3.2. Formulation and optimization of tetrabenazine solid dispersions 20
3.2.1. Formulation and optimization of tetrabenazine binary solid dispersions 20
3.2.2. Formulation and optimization of tetrabenazine pH-modified ternary solid dispersions 22
3.3. Tetrabenazine solid dispersions morphology and solid-state characterization 23
3.3.1. FT-IR Spectroscopic Analysis 23
3.3.2. Powder X-ray diffraction (PXRD) analysis 26
3.3.3. Differential scanning calorimetry (DSC) analysis 26
3.3.4. Field emission scanning electron microscope (FE-SEM) images 30
3.4. Powder properties 30
3.5. Physicochemical properties of FDTs 34
3.5.1. Physical properties of FDTs 34
3.5.2. Optimization of in vitro disintegration time of FDTs 36
3.6. Dissolution profiles of FDTs 38
3.7. PXRD analysis of granules and tablets 40
3.8. Stability study 42
4. Conclusions 44
Chapter 2: Development of Self-Nanomicellizing Solid Dispersions based on Gelatin oleic acid conjugates for Synergistic Solubility and Permeability Enhancement 45
1. Introduction 45
2. Materials and Methods 47
2.1. Materials 47
2.2. Synthesis of GOC . 48
2.3. Solubility study of TBZ and GOC 48
2.4. Inhibition of recrystallization study 48
2.5. Preparation of binary solid dispersions 49
2.6. Preparation of ternary solid dispersions 49
2.7. Characterization of GOC and Formulations 51
2.7.1. Proton Nuclear Magnetic Resonance (1H NMR) 51
2.7.2. Degree of Substitution (DS) determination 51
2.7.3. Critical Micelle Concentration (CMC) determination 51
2.7.4. Field emission scanning electron microscope (FE-SEM) 52
2.7.5. Field emission transmission electron microscope (FE-TEM) 52
2.7.6. Fourier Transform Infrared Spectroscopy (FT-IR) 52
2.7.7. Powder X-ray Diffraction (PXRD) 52
2.7.8. Differential Scanning Calorimetry (DSC) 53
2.7.9. Characterization of GOC nanoparticles 53
2.8. In vitro release test 53
2.9. In vitro permeability study 54
2.10. HPLC analysis 54
3. Results and discussions 55
3.1. Solubility of drug and excipients 55
3.2. GOC synthesis 57
3.3. Critical micelle concentration (CMC) determination 59
3.4. Inhibition of recrystallization study 59
3.5. GOC and solid dispersion physicochemical characterization 62
3.5.1. Morphology of GOC and GOC based solid dispersions nanoparticles 62
3.5.2. FT-IR analysis 64
3.5.3 PXRD analysis 66
3.5.4 DSC analysis 68
3.6. Characterization of GOC nanoparticles 70
3.7. In vitro Release Study 73
3.8. In vitro Permeability Study 76
4. Conclusions 79
5. References 80