声明
Chapter 1 Research background
1.1 Introduction
1.2 Paclitaxel injections already available on the market
1.2.1 Conventional paclitaxel injection (Taxol)
1.2.2 Paclitaxel liposome
1.2.3 Paclitaxel in albumin-bound form
1.2.4 Paclitaxel polymeric micelles for injection
1.3 New formulations of paclitaxel in phase I-III clinical trials
1.3.1 Paclitaxel liposome LEP-ETU
1.3.2 Cationic liposome containing paclitaxel-EndoTAG-1 liposome
1.3.3 Paclitaxel micellar nanoparticles with long cycle-NK105
1.3.4 Oral formulation of paclitaxel-DHP107
1.4 New formulations of paclitaxel
1.4.1 Prodrugs
1.4.2 Gel
1.4.3 Emulsion
1.4.4 Cyclodextrin inclusion compound
1.4.5 Drug-eluting stents
1.5 New non-injectable formulations of paclitaxel
1.5.1 Polymeric nanoparticles
1.5.2 Composite micelles
1.5.3 Nanocrystals
1.5.4 Microcapsules
1.5.5 Nanoemulsions
1.5.6 Flexible liposomes
1.6 Research design
Chapter 2 Formulation Screening of Paclitaxel Injection
2.1 Instruments and Materials
2.1.1 Instruments
2.1.2 Materials
2.2 Methods method
2.2.1 Related substances
2.2.2 Assay
2.3 Selection of categories of solvents
2.3.1 Screening of Solvents
2.3.2 Screening of pH regulator content
2.3.3 Assay determination of citric acid
2.3.4 Material compatibility
2.4 Summary
Chapter 3 Proposed Formulation Technology and Parameters of Paclitaxel Injection
3.1 Instruments and Materials
3.1.1 Instruments
3.1.2 Materials
3.2 Dissolution temperature screening
3.2.1 Preparation of Samples with Different Concentrations
3.2.2 Results and discussion
3.4 Activated carbon adsorption test
3.4.1 Material preparation
3.4.2 Results and discussion
3.5 Screening of sterilization conditions
3.5.1 Hot pressing sterilization
3.5.2 Material selection for bactericidal filtration membrane
3.6 The final workflow
3.7 Summary
Chapter 4 Establishment of Quality Standard and Validation of Paclitaxel Injection
4.1 Instruments and Materials
4.1.1 Instruments
4.1.2 Materials
4.2 Physico-chemical test
4.2.1 Identification
4.2.2 pH value
4.2.3 Moisture content
4.2.4 Osmolality
4.2.5 Nsoluble particles
4.3 Establishment of method for related substances
4.3.1 Screening test conditions
4.3.2 Determining of known impurities
4.3.3 Method comparison
4.3.4 Validation of related substances and methods
4.4 Establishment of method for determination of the content
4.4.1 Chromatographic conditions of assay determination
4.4.2 Comparison of assay determination method
4.4.3. Screening of mobile phase ratio
4.4.4 Determination of solvents
4.4.5 Concentration of tested solution and the reference solution
4.4.6 Injection volume and column temperature
4.4.7 System suitability
4.4.8 Proposed assay determination method
4.5 Methodological verification of sterility test
4.5.1 Aseptic Methodology Verification Process
4.5.2 Determination of the method of sterility test
4.5.3 Results and discussion
4.6 Methodological verification of bacterial endotoxin test
4.6.1 Formulation of standard
4.6.2 Methodological verification of bacterial endotoxin test
4.6.3 Results and discussion
4.7 Summary
Chapter 5 Stability Test of Paclitaxel Injection
5.1 Instruments and Materials
5.1.1 Instruments
5.1.2 Materials
5.2 Stability studies of paclitaxel injection diluting with lipid emulsion
5.2.1 Test operation process
5.2. 2 Results and discussion
5.3 Stability test of preparation
5.3.1 60 ℃ test of influencing factors
5.3.2 40 ℃ accelerated stability test
5.3.3 Long term test
5.4 Summary
Chapter 6 Pharmacokinetics of Paclitaxel Injection
6.1 Instruments and Materials
6.1.1 Instruments
6.1.2 Materials
6.2 Experimental methods and conclusions
6.2.1 Plasma sample process
6.2.2 LC-MS/MSConditions
6.2.3 Methodological investigation
6.2.4 Pharmacokinetics of paclitaxel injection in SD rats
6.3 Summary
Chapter 7 Conclusion
参考文献
Publications
致谢
天津大学;
