Title Page
Contents
SYMBOLS AND ABBREVATIONS 10
VITA 13
PUBLICATIONS 14
ABSTRACT 15
CHAPTER 1. INTRODUCTION 17
1.1. Introduction 18
1.1.1. Water-soluble polymers and applications 18
1.1.2. Cellulose and cellulose derivatives 21
1.1.3. Characteristics of HPMC and applications 24
1.2. Organization of dissertation 29
CHAPTER 2. HPMC-BASED HYDROGEL AS A TRANSDERMAL DRUG DELIVERY SYSTEM IN COSMECEUTICAL FIELDS 30
2.1. Introduction 31
2.2. Materials and methods 35
2.2.1. Reagents and materials 35
2.2.2. Preparation of hydrogel 36
2.2.3. Morphological characterization of hydrogel 38
2.2.4. Analysis of physico-chemical properties 38
2.3. Results and discussion 39
2.3.1. Morphological characteristics of HPMC based hydrogel 39
2.3.2. Control of hydrogel physico-chemical factors 41
2.3.3. Release profile of niacinamide from hydrogels 43
2.3.4. Composition optimizes 45
2.4. Conclusion 46
CHAPTER 3. ENHANCED SOLUBILITY THROUGH PARTICLE SIZE CONTROL, MODIFICATION OF CRYSTAL BEHAVIOR, AND CRYSTALLINE FORM CHANGES IN SOLID DISPERSION OF NIFEDIPINE 48
3.1. Introduction 49
3.2. Materials and methods 53
3.2.1. Reagents and materials 53
3.2.2. Solid dispersion preparation 53
3.2.3. Morphological characterization of solid dispersion 56
3.2.4. Crystallinity analysis 56
3.2.5. Drug release rate measurement 57
3.3. Results and discussion 58
3.3.1. Morphological characteristics of solid dispersions 58
3.3.2. Crystallographic analysis of solid dispersions 60
3.3.3. Drug release behavior of nifedipine 66
3.4. Conclusion 69
CHAPTER 4. CONCLUSION AND FUTURE WORKS 70
4.1.1. Conclusions 71
4.1.2. Future works 72
REFERENCES 74
Table 1-1. Classification of water-soluble polymers 19
Table 1-2. Function and application of water-soluble polymer 20
Table 1-3. HPMC grade (USP) 24
Table 1-4. Recommendation of pharmaceutical applications 26
Table 1-5. Recommendation of pharmaceutical applications 27
Table 2-1. The compositions of hydrogel samples (Solid content 5 %, w/w). Designed as a competitive hydrogel* (Existing formulation, Solid content 2%, w/w) 37
Table 2-2. Equilibrium swelling ratios(ESR) of hydrogels 42
Table 3-1. Spray-drying conditions 55
Figure 1-1. Wood products and application of cellulose 22
Figure 1-2. HPMC structure and process according to viscosity 25
Figure 2-3. Applications of cellulose-based hydrogels 32
Figure 2-4. HPMC-based hydrogel as a transdermal drug delivery system for active ingredients 33
Figure 2-5. The chemical formula of the niacinamide as an active ingredient. 35
Figure 2-6. Simplex design plot by mixture design with HPMC, algae extract (Carrageenan) and gum additive (LBG). 36
Figure 2-7. Analytical methods for investigating physico-chemical properties of hydrogel samples (A) Texture analyzer (B) Franz diffusion cell system 39
Figure 2-8. SEM analysis of hydrogel S7 and Competitor 40
Figure 2-9. Gel hardness (GH) and elongation(E) of hydrogels 41
Figure 2-10. Gel adhesive force (GAF) of hydrogels 42
Figure 2-11. Release profile of the active ingredient(niacinamide) from hydrogels 44
Figure 2-12. Cox reaction trajectory and overlaid contour plots regarding GH, GAF, ESR 45
Figure 3-13. Preparation method of solid dispersions 50
Figure 3-14. Examples of spray dried therapeutics 50
Figure 3-15. The chemical structure of nifedipine 51
Figure 3-16. Scheme of the spray-drying manufacturing method: Feed ①, Spray-drying chamber ②, Separating ③, and Spray-dried product ④. 54
Figure 3-17. Particle forms of nifedipine raw material and solid dispersions containing various polymers. (A) Nifedipine, (B) PVP, (C) Eudragit E100, (D)... 59
Figure 3-18. X-ray diffraction graph of solid dispersions containing nifedipine raw materials and polymers. (A) Nifedipine (yellow), PVP (dark blue),... 65
Figure 3-19. Drug release rate of nifedipine raw material and polymer-containing solid dispersions. Graph shows dissolution results for nifedipine raw... 68