Mô hình hóa quá trình trích ly 10 deaccetylbaccatin iii từ taxus wallichiana zucc sử dụng chất lỏng siêu tới hạn

ĐẠI HỌC QUỐC GIA TP HCM TRƢỜNG ĐẠI HỌC BÁCH KHOA NGUYỄN QUANG DUY MƠ HÌNH HĨA Q TRÌNH TRÍCH LY 10DEACCETYLBACCATIN III TỪ TAXUS WALLICHIANA ZUCC SỬ DỤNG CHẤT LỎNG SIÊU TỚI HẠN Chuyên ngành : Quá trình Thiết bị CNHH LUẬN VĂN THẠC SĨ TP Hồ Chí Minh, tháng 05 năm 2011 CƠNG TRÌNH ĐƯỢC HỒN THÀNH TẠI TRƯỜNG ĐẠI HỌC BÁCH KHOA –ĐHQG -HCM Cán hướng dẫn khoa học : TS Lê Thị Kim Phụng Cán chấm nhận xét : PGS TS Phạm Thành Quân (Ghi rõ họ, tên, học hàm, học vị chữ ký) Cán chấm nhận xét : TS Mai Thanh Phong (Ghi rõ họ, tên, học hàm, học vị chữ ký) Luận văn thạc sĩ bảo vệ Trường Đại học Bách Khoa, ĐHQG Tp HCM ngày 27 tháng 05 năm 2011 Thành phần Hội đồng đánh giá luận văn thạc sĩ gồm: (Ghi rõ họ, tên, học hàm, học vị Hội đồng chấm bảo vệ luận văn thạc sĩ) PGS.TS.Phan Đình Tuấn PGS.TS Phạm Thành Quân TS Mai Thanh Phong TS Lê Thị Kim Phụng TS Hoàng Ngọc Hà Xác nhận Chủ tịch Hội đồng đánh giá LV Trưởng Khoa quản lý chuyên ngành sau luận văn sửa chữa (nếu có) CHỦ TỊCH HỘI ĐỒNG TRƢỞNG KHOA KTHH ĐẠI HỌC QUỐC GIA TP.HCM TRƢỜNG ĐẠI HỌC BÁCH KHOA CỘNG HÒA XÃ HỘI CHỦ NGHĨA VIỆT NAM Độc lập - Tự - Hạnh phúc NHIỆM VỤ LUẬN VĂN THẠC SĨ Họ tên học viên: NGUYỄN QUANG DUY MSHV: 09290975 Ngày, tháng, năm sinh: 28 – 01 – 1986 Nơi sinh: Bình Phước Chuyên ngành: Quá trình Thiết bị CNHH Mã số : I.TÊN ĐỀ TÀI: MƠ HÌNH HĨA Q TRÌNH TRÍCH LY 10-DEACCETYLBACCATINB III TỪ THÔNG ĐỎ SỬ DỤNG CHẤT LỎNG SIÊU TỚI HẠN (Mathematical modeling the supercritical fluid extraction of 10-deaccetylbaccatin III from Taxus Wallichiana Zucc) II.NHIỆM VỤ VÀ NỘI DUNG: Tổng quan tài liệu kỹ thuật trích ly xây dựng mơ hình tốn học q trình trích ly sử dụng chất lỏng siêu tới hạn Xây dựng mơ hình tốn học mơ tả đường cong trích ly 10-DAB III từ thông đỏ sử dụng chất lỏng siêu tới hạn Đánh giá ảnh hưởng thông số cơng nghệ đến động học q trình trích ly 10-DAB III từ thơng đỏ Mơ đường cong trích ly 10-DAB III từ thông đỏ III.NGÀY GIAO NHIỆM VỤ : 01/07/2009 IV.NGÀY HOÀN THÀNH NHIỆM VỤ: 27/05/2011 V.CÁN BỘ HƢỚNG DẪN : TS LÊ THỊ KIM PHỤNG Tp HCM, ngày 19 tháng 05 năm 2011 CÁN BỘ HƢỚNG DẪN (Họ tên chữ ký) CHỦ NHIỆM BỘ MÔN ĐÀO TẠO (Họ tên chữ ký) TRƢỞNG KHOA KỸ THUẬT HÓA HỌC ACKNOWLEDGEMENTS I would like to express my sincere gratitude to my supervisor, Dr Le Thi Kim Phung for the continuous support of my master study and research, for her patience, motivation, enthusiasm, and immense knowledge Her guidance helped me in all the time of research and writing of this thesis I could not have imagined having a better advisor and mentor for my study I would like to give my appreciation to the teaching staff of Chemical process Department, lab mates and students who helped me in research implementation I would like to give my sincere thanks to all of you Nguyen Quang Duy i ABSTRACT 10-deaccetylbaccatin III, a diterpenoid extracted from Taxus spp., is a practical solution for preparing Paclitaxel which has been used as efficient drug for lung and breast cancer treatment The available and potential research scheme for the supercritical fluid extraction (SFE) of 10deaccetylbaccatin III, an innovative technique with a great deal of advantages, was drawn out in this work Mathematical modeling and simulating of the extraction process is completely novel research with significant desire The model based on the concept of broken and intact cell was employed and developed for describing the overall extraction curve with high agreement to experimental data The internal mass transfer coefficient in the solid matrix was estimated within the mathematical model and integrated in correlation with extraction pressure, temperature and flow rate in terms of statistical modeling with quadratic order model The integration of mathematical and empirical model is a new approach that allows us to simulate the supercritical carbon dioxide extraction of 10-DAB III The kinetic data, mathematical model and simulation tool for SFE of 10-DAB III are proposed for the first time and they are expected to be useful for optimizing as well as investigating scale up methodology TĨM TẮT 10-deaccetylbaccatin III diterpenoid có giống thông đỏ, ứng dụng sản xuất thuốc điều trị ung thư Paclitaxel Tình hình nghiên cứu q trình trích ly Paclitaxel từ thơng đỏ tổng hợp phân tích nhằm xác định hướng nghiên cứu tiềm cần thực Trong đó, mơ hình hóa q trình trích ly sử dụng chất lỏng siêu tới hạn đề tài cần quan tâm Trong luận văn này, mơ hình tốn học dựa giả thuyết hạt vật liệu bị phá vỡ ứng dụng phát triển để mô tả đường cong trích ly với độ tương thích cao, từ xác định hệ số truyền khối pha rắn Phương pháp quy hoạch thực nghiệm bậc hai với thí nghiệm tâm sử dụng để xây dựng mối quan hệ hệ số truyền khối pha rắn với thơng số vận hành Thơng qua đó, mơ hình tốn học mơ hình thống kê kết hợp để xây dựng công cụ mô đường cong trích ly 10-DAB III từ thơng đỏ Taxus Wallichiana Zucc Các thơng số động học, mơ hình tốn học mô áp dụng phát triển luận văn mang tính mới, bổ sung thiếu sót nghiên cứu trích ly 10DAB III sử dụng chất lỏng siêu tới hạn, đồng thời áp dụng để giải tốn tối ưu phục vụ cho nghiên cứu phương pháp scale up ii LỜI CAM ĐOAN Tôi xin cam đoan kết trình bày luận án tơi thực từ kiến thức Tơi khơng nộp luận án cho trường, viện để cấp Nguyễn Quang Duy iii CONTENTS ACKNOWLEDGEMENTS i CONTENTS iv ABSTRACT ii NOMENCLATURE vi LIST OF FIGURES viii LIST OF TABLES ix Chapter 1: INTRODUCTION 1.1 Why is SFE of 10-DAB III? 1.2 Why is mathematical modeling? 1.3 Objectives Chapter 2: LITERATURE REVIEW 2.1 Paclitaxel story from academic viewpoint 2.1.1 Paclitaxel (Taxol) 2.1.2 Extraction of Paclitaxel from Taxus spp 2.1.3 Total synthetic of Paclitaxel 2.1.4 10-Deaccetylbaccatin III and Semisynthetic of Paclitaxel 11 2.1.5 Conventional solvent extraction of Paclitaxel and 10-DAB III 13 2.1.6 Accelerated solvent extraction 16 2.1.7 Microwave assisted extraction 17 2.2 Supercritical fluid technology – an innovative technique 19 2.2.1 Supercritical fluids 19 2.2.2 Thermodynamic 21 2.2.3 Physical properties 24 2.2.4 Supercritical fluid applications 24 2.3 Supercritical fluid extraction 29 2.3.1 SFE apparatus 29 2.3.2 Advantages of SFE 30 2.3.3 Process parameters 32 2.3.4 Applications 36 2.3.5 SFE of Paclitaxel and 10-DAB III 37 2.4 Mathematical modeling the extraction curve 39 2.4.1 Extraction mechanism 39 2.4.2 Published models in prior art 40 Chapter 3: EXPERIMENTAL STRATEGY 49 3.1 Materials 49 3.1.1 Taxus Wallichiana Zucc 49 3.1.2 Chemicals 51 3.2 Supercritical fluid extraction 52 3.2.1 Supercritical fluid extraction apparatus 52 3.2.2 Design of experiments (DOE) 53 3.2.3 HPLC analysis 54 3.3 Physical properties of the solid material 55 3.3.1 Solid density 55 3.3.2 Bed void fraction 55 Chapter 4: EXPERIMENTAL RESULTS 56 iv 4.1 Supercritical CO2 extraction 56 4.1.1 Effects of co-solvent 56 4.1.2 Effects of temperature 58 4.1.3 Effects of flow rate 59 4.1.4 Effects of pressure 60 Chapter 5: MATHEMATICAL MODELING 62 5.1 Model equations 62 5.1.1 Mass balance equations 62 5.1.2 Mass transfer 65 5.1.3 Algorithm 66 5.2 Model parameters 68 5.2.1 Initial solute concentration in fluid phase y0 and solid matrix x0 68 5.2.2 Solubility of solutes in SFs 69 5.2.3 Solvent density 71 5.2.4 Solvent viscosity 73 5.2.5 External mass transfer coefficient 76 5.2.6 Fitting parameters 79 5.3 Modeling results 82 5.3.1 Model evaluation 82 5.3.2 Model validating 85 5.3.3 Effects of pressure 86 5.3.4 Effects of temperature 88 Chapter 6: Internal mass transfer coefficient evaluation 90 6.1 Experimental data 90 6.2 Analysis of variance (ANOVA) 91 6.3 Effects of operating conditions on internal mass transfer coefficient 93 Chapter 7: OVERALL EXTRACTION CURVE SIMULATION 95 7.1 Dimensionless fluid phase concentration 95 7.2 Simulation of OEC 96 Chapter 8: CONCLUSIONS AND RECOMMENDATIONS 100 8.1 Conclusions 100 8.2 Recommendations 101 v NOMENCLATURE a0: specific surface area per unit volume of extraction bed (m2/m3) as: specific area between the regions of intact and broken cells (m2/m3) d: particle diameter (m) e: extraction yield (kg (extract) kg (insoluble solid)-1) E: extract (kg) h: axial co-ordinate (m) H: extraction bed length (m) i: number of mixer (also as a subscript) jf: flux from broken cells to solvent (kgm-3s-1) js: flux from intact cells to broken cells (kgm-3s-1) Jf: (=jftr/[fεy0]) dimensionless flux from broken cells to solvent Js: (=jstr/[s(1-ε)x1,0]) dimensionless flux from intact cells to broken cells kf: fluid-phase mass transfer coefficient (s-1) ks : solid-phase mass transfer coefficient (s-1) K: partition coefficient ̅ : (=K1,0 /y0) partition constant in the dimensionless model equations n: number of mixers in series N: solid charge in the extractor (kg) Nm: (=(1-cu)N) charge of insoluble solid (kg) q: relative amount of the passed solvent (kg(solvent) kg(insoluble solid)-1) Q: solvent flow rate (kgs-1) r: grinding efficiency Rs: slope ratio (extraction curve slope at e≠0 to the slope at e=0) t: extraction time (s) tr: (=H/U) solvent residence time (s) U: interstitial fluid velocity (ms-1) xu: concentration in the untreated solid ( kg(soluble) kg(insoluble solid)-1) xt: transition concentration (kg(soluble) kg(insoluble solid)-1) x1: concentration in broken cells (kg(soluble) kg(insoluble solid)-1) x1,0: initial concentration in broken cells (kg(soluble) kg(insoluble solid)-1) vi x2: concentration in intact cells (kg(soluble) kg(insoluble solid)-1) x2,0: initial concentration in intact cells (kg(soluble) kg(insoluble solid)-1) Xi: (=xi/x1,0) dimensionless concentration in the untreated solid Xt: (=xt/x1,0) dimensionless transition concentration X1: (=x1/x1,0) dimensionless concentration in broken cells X2: (=x2/x1,0) dimensionless concentration in intact cells y: fluid-phase concentration (kg(soluble) kg(solvent)-1) y0: initial fluid-phase concentration (kg(soluble) kg(solvent)-1) ys: solubility (kg(soluble) kg(solvent)-1) y*(x1): equilibrium fluid-phase concentration (kg(soluble) kg(solvent)-1) Y: (=y/y0 dimensionless fluid-phase concentration Ys: (=ys/y0) dimensionless solubility Y*(X1): dimensionless equilibrium fluid-phase concentration z: (=h/H), dimensionless axial co-ordinate Greek letters : (e) weight of plug flow model in the estimate of extraction curve : (=fε/[s(1-ε)] solvent-to-matrix ratio in the bed (kg(solvent) kg(insoluble solid)-1) : (=y0/(rx1,0)) initial solute distribution between solvent and broken cells ε: bed void fraction e: (=/(kfaotr)) dimensionless external mass transfer resistance i: (=(1-ε)/(ksa0tr)) dimensionless internal mass transfer resistance f: solid density (kgm-3) s: solid density ( Kg(insoluble solid) m(solid phase)-3) : (=t/tr), dimensionless time r: fictional starting time of extraction from intact cells in approximate model : (-E/(NCu)) dimensionless extraction yield vii Chapter – Overall extraction curve simulation The obtained data would provide the information of suitable operating parameters For e.g., the calculated OEC at 100bar, 313K, 15g/min has the linear portion followed by a curve portion Due to the slope of the curve portion is significant low, the increase of extraction yield is negligible from the point of 25g/g solvent used The extraction assays thus can be finished at which the solvent consumption reach to 25g/g without any significant effect on the extraction yield Based on the information of solvent consumption, we would be able to distinguish the target flow rate and extraction time The effects of pressure and temperature are also reflected quantifiably in the calculated OEC so that we can operate the process at desired conditions All of model parameters such as mass transfer in fluid and solid phase, solvent density and viscosity, solubility are integrated in correlation with operating conditions Therefore, optimization problem would be formulated and solved numerically The above data are obtained within the dimensionless model equation For investigating scale up methodology, following approach can be applied: Employing original model equations to take into account the effect of extractor dimension Calculating OEC up to desired proposal For example, if the proposal is that the ratio of solvent mass and material mass is maintained at constant value, then the solvent flow rate or the extraction time will be adjusted to calculate the OEC within model equations Other scale up proposals can be performed by adjusting model parameters In fact, this tool is just valid for products possessing similar extraction behavior For other products, similar approach can be applied with adjusting in model equation for the right initial concentration in fluid phase and broken cell; then the internal mass transfer coefficient evaluation is required to be performed Page 99 Chapter – Conclusions and recommendations Chapter 8: 8.1 CONCLUSIONS AND RECOMMENDATIONS Conclusions The SFE process yielded a great efficient for the recovery of natural derivatives with a great deal of advantages Its major advantages are great extraction yield, organic solvent – free, and the feasibility of recycling CO2 as well as online monitoring and analyzing Supercritical carbon dioxide extraction of 10-DAB III from Taxus Wallichiana Zucc with the addition of ethanol was studied in this work The effects of entrainer, pressure, temperature, and flow rate on the extraction yield and kinetics were investigated Ethanol expresses a positive impact on extraction yield The increase in the ratio of ethanol to total solvent flow rate enhanced the yield of 10-DAB III significantly It was due to the solvent polarity was manipulated, thus the solubility of 10-DAB III in supercritical solvent was improved, resulting in the enhancement of extraction efficiency The use of friendly solvent such as ethanol will not cause negative impact on health and environment Pressure and temperature have the significant effects on the extraction yield At any temperature, the increase of pressure enhances the solubility and extraction efficiency of 10-DAB III since the solvent density and thus the solvent power are increased The effect of temperature is remarked only at high pressure due to the crossover effect of temperature and pressure to solvent density and solubility of the solute The overall extraction curve was modeled within a mathematical model based on the concept of broken and intact cell The solid particle is divided into two parts caused by pretreatment process: the broken cell containing free solutes and the core containing solutes – matrix interaction The model is a versatile tool for the SFE simulation as it includes flexible relationships both for phase equilibrium and flow pattern The main practical advantage of the model is its ability to simulate different types of extraction curves and characterize them with mutually comparable parameters as mass transfer coefficients and equilibrium constants The model validation was also performed and illustrated that the proposed model is suitable for simulating the OEC at low deviation The BIC model allows us to evaluate the extraction mechanism and kinetics In terms of fitting the model to experimental data, we estimated the internal mass transfer coefficient as well as the transaction point from the first stage of the extraction process controlled by external mass transfer Page 100 Chapter – Conclusions and recommendations in fluid to the second one governed by internal mass transfer The calculated internal mass transfer coefficient is novel kinetic data for SFE of 10-DAB III which can be used for evaluating the effects of operating parameters to the extraction process and proposing scale up methodology At least one set of experimental data is required for calculating the internal mass transfer coefficient at given operating condition using the BIC model That drawback causes inconvenience for simulating the extraction process Therefore, in this work, the correlation of internal mass transfer coefficient in solid phase and operating condition was estimated within the statistical modeling Quadratic order model with central composite design was employed for the formulation of empirical correlation of internal mass transfer coefficient and operating condition including pressure, temperature and flow rate The mutual effect of operating parameters to extraction yield and kinetic data within the regression equation is agreed with the one characterized by extraction mechanism The regression equation is a mathematical tool for estimating the data of internal mass transfer at desired value of operating parameters which are in investigated range whilst the solid structure is not generally defined This is a completely new approach and expected to be applied for other products In terms of the model and empirical correlation of internal mass transfer coefficient, the supercritical fluid extraction of 10-DAB III was simulated At given operating condition, the extraction curve was calculated based on the data of internal mass transfer estimated from proposed empirical correlation, other parameters were calculated or available in literature The simulation tool is very useful for optimizing the extraction process where the operating condition and extraction time can be identified 8.2 Recommendations In this work, the solubility was estimated as the slope of the linear portion of the extraction curve It is useful especially in the case of lacking solubility data To minimize the deviation, the solubility should be obtained within experimental assays The grinding efficient or the initial partition of broken and intact cell is an important parameter for modeling the extraction curve In this work, it is estimated from the approximately model It is recommended that this value should be obtained within SEM image of treated material The graphical user interface for model and simulation tool is highly desirable Page 101 LIST OF PUBLICATIONS Nguyen Quang Duy, Phan Dinh Tuan, Le Thi Kim Phung, Supercritical fluid extraction of taxol and 10-deacetylbaccatin III from the leaves of year old Taxus Wallichiana Zucc, Journal of science and technology, Vietnam, 48, 2010 Nguyen Quang Duy, Siti Machmudah, Mitsuru Sasaki, Motonobu Goto, Phung Kim Le, Supercritical fluid extraction of Paclitaxel and 10-Deacetylbaccatin III from Taxus Wallichiana Zucc, International Symposium on ChE , Fukuoka, Japan, Dec, 2010 Nguyen Quang Duy, Phan Dinh Tuan, Le Thi Kim Phung, Supercritical fluid extraction of paclitaxel and 10-deacetylbaccatin III from taxus wallichiana zucc: multivariate statistical modelling, 1st International conference in chemical and environmental engineering, Kular Lumpur, Malaysia, Nov, 2010 Nguyen Quang Duy, Phan Dinh Tuan, Le Thi Kim Phung, Mathematical modeling of supercritical fluid extraction of 10-deacetylbaccatin III from cultivated taxus wallichiana zucc, The 3nd Regional Conference on the Interdisiplinary Research on Natural Resources and Materials, Langkawi, Malaysia, Oct, 2010 Nguyen Quang Duy, Phan Dinh Tuan, Le Thi Kim Phung, An alternative taxol resource from year old Taxus Wallichiana Zucc cultivated in dalat, Vietnam, 3rd International Student Conference on Advanced Science and Technology (ICAST, Seoul, Korea, Dec, 2009 8-26 REFERENCES Akgerman, A a G., M (1994) Fundamentals of Solids Extraction by Supercritical Fluids Supercritical Fluids - Fundamentals for Applications J M H K Sengers, E., Klüwer Academic Publishers: 669-696 Aleksovski, S A and H Sovová (2007) "Supercritical CO2 extraction of Salvia officinalis L." The Journal of Supercritical Fluids 40(2): 239-245 Appendino, G (1995) The Chemistry and Pharmacology of Taxol and Its Derivatives, Elsevier Science Bala, S., G C Uniyal, et al (1999) "Analysis of taxol and major taxoids in Himalayan yew, Taxus wallichiana." Journal of Chromatography A 858(2): 239-244 Brachet A, R S., Mateus L, Christen P and Veuthey J (2001) "Optimisation of accelerated solvent extraction of cocaine and benzoylegonine from coca leaves." Journal of Separation science 24(1): 865-873 Brunner, G (1984) "Mass transfer from solid material in gas extraction." Physical Chemistry 88(1): 887-891 Campos, L M A S., E M Z Michielin, et al (2005) "Experimental data and modeling the supercritical fluid extraction of marigold (Calendula officinalis) oleoresin." The Journal of Supercritical Fluids V EBFS V Encontro Brasileiro de Fluidos Supercriticos V Brazilian Meeting on Supercritical Fluids 34(2): 163-170 Chun, M.-K., H.-W Shin, et al (1996) "Supercritical fluid extraction of paclitaxel and baccatin III from needles of taxus cuspidata." The Journal of Supercritical Fluids 9(3): 192-198 Chung-sung tan, s.-k l a d.-c l (1988) "Fluid-Solid Mass Transfer in a Supercritical Fluid Extractor." The Chemical Engineering Journal 38(1): 17-22 Denis R Laurena, D J J a J A D (1995) "Analysis of taxol, 10-deacetylbaccatin III and related compounds in Taxus baccata." Journal of Chromatography A 712(2): 303-309 E.M Phillips, V J S (1993) "Rapid expansion from supercritical solutions: application to pharmaceutical processes." International Journal of Pharmaceutics 94(1): 1-10 F Esmaeilzadeh, H A a., M Lashkarbolooki (2009) "Calculation of the solid solubilities in supercritical carbon dioxide using a new Gex mixing rule." Journal of Supercritical Fluids 51(1): 148-158 Fidalgo-Used N., B.-G E a S.-M (2007) "Sample handling strategies for the determination of persistent trace organic contaminants from biota samples." Analytica Chimica Acta 590(1): 1-16 Fiori, L., D Basso, et al (2008) "Seed oil supercritical extraction: Particle size distribution of the milled seeds and modeling." The Journal of Supercritical Fluids 47(2): 174-181 Fiori, L., D Basso, et al (2009) "Supercritical extraction kinetics of seed oil: A new model bridging the [`]broken and intact cells' and the [`]shrinking-core' models." The Journal of Supercritical Fluids 48(2): 131-138 8-27 Fuchs, D A a J., Randall K (1978) "Cytological evidence that taxol, an antineoplastic agent from Taxus brevifolia, acts as a mitotic spindle poison." Cancer Treatment Reports 62(8): 12191222 Fumio Kawamura, Y K., Tatsuro Ohira, and Mitsuyoshi Yatagai (1999) "Accelerated Solvent Extraction of Paclitaxel and Related Compounds from the Bark of Taxus cuspidata." Journal of Natural Products 62(1): 244-247 G, K (1983) Manual of cultivated conifers, Verlag Paul Parey Goodman, J W., Vivien (2001) "Nature and Politics in the Pursuit of an Anti-Cancer Drug." Cambridge University Press: 17 Herrero, M., J A Mendiola, et al (2010) "Supercritical fluid extraction: Recent advances and applications." Journal of Chromatography A Extraction Techniques 1217(16): 2495-2511 Hideki Tanaka, K N (1994) "Solubility in supercritical fluid mixtures with co-solvents: an integral equation approach." Fluid Phase Equilibria 102(1): 107-120 Huang, C H O (1986) "New Taxanes from Taux Brevifolia." Journal of Natural Products 49(4): 665-669 Hyun J.E., K J H (2008) "Microwave-assisted extraction of paclitaxel from plant cell cultures." Korean Journal of Biotechnology and Bioengineering 23(4): 281-284 Irene Pasquali, R B a F G (2006) "Solid-state chemistry and particle engineering with supercritical fluids in pharmaceutics." European Journal of Pharmaceutical Sciences 27(4): 299-310 Janete H Y Vilegas, F M L., Wagner Vilegas, Gilberto L Pozetti (1993) "Off-line supercritical fluid extraction—high resolution gas chromatography applied to the study of moraceae species." Phytochemical Analysis 4(5): 230-234 Jennings, D., Deutsch, HM, Zalkow, LH, and Teja (1992) "Supercritical extraction of taxol from the bark of Taxus brevifolia." Journal of Supercritical fluids 5(1): 1-6 Jhonston, D J D a K P (1997) Encyclopedia of Separation Technology, John Wiley Jia, D., S Li, et al (2009) "Supercritical CO2 extraction of Plumula nelumbinis oil: Experiments and modeling." The Journal of Supercritical Fluids 50(3): 229-234 Kaufmann B, C P a V J (2001) "Parameters affecting microwave-assisted extraction of withanolides." Phytochemistry Analysis 12(1): 327-331 Kingston, D G I., A G Chaudhary, et al (1994) "Synthesis of taxol from baccatin III via an oxazoline intermediate." Tetrahedron Letters 35(26): 4483-4484 Koppaka, V R (1993) "Taxol and Related Taxanes, I Taxanes of Taxus brevifolia Bark." Journal of Pharmaceutical research 10(4): 521-524 Krukonis, V (1984) "Supercritical fluid nucleation of difficult-to-comminute solids." Proc Annual Meeting AIChE: 140 Kubátová, A., Jansen, B., Vaudoisot, J.F., Hawthorne, S.B (2002) "Thermodynamic and kinetic models for the extraction of essential oil from savory and polycyclic aromatic hydrocarbons from soil with hot (subcritical) water and supercritical 8-28 CO2." Journal of Chromatography A 975(1): 175-188 Li, S., H Zhang, et al (2001) "Taxane diterpenoids from the bark of Taxus yunnanensis." Phytochemistry 58(2): 369-374 Luque de Castro, M D., & Garcia-Ayuso, L E (1998) "Soxhlet extraction of solid materials: An outdated technique with a promising innovative future." Analytica Chimica Acta 369(1): 110 M Letellier, H B., J Bellocq, J Connan (1999) "Focused microwave-assisted extraction of polycyclic aromatic hydrocarbons and alkanes from sediments and source rocks." Organic Geochemistry 30(11): 1353-1365 M Perrut, J Y C., M Poletto, R Reverchon (1997) "Mathematical modeling of sunflower seed extraction by supercritical CO2." Industrial and Engineering Chemistry Research 36(1): 430-436 M.J Meziani, P P., F Beacham, L.F Allard, Y-P Sun (2005) "Nanoparticle formation in rapid expansion of water-in-supercritical carbon dioxide micro emulsion into liquid solution." Journal of Supercritical Fluids 34(1): 91-97 Machmudah, S., A Sulaswatty, et al (2006) "Supercritical CO2 extraction of nutmeg oil: Experiments and modeling." The Journal of Supercritical Fluids 39(1): 30-39 Macías-Sánchez, M D., C M Serrano, et al (2009) "Kinetics of the supercritical fluid extraction of carotenoids from microalgae with CO2 and ethanol as cosolvent." Chemical Engineering Journal 150(1): 104-113 Mansukhlal C Wani, H L T., Monroe E Wall, Philip Coggon, Andrew T McPhail (1971) "Plant antitumor agents VI Isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia." American Chemical Society 93(9): 2325–2327 Marcus, Y (2006) "Are solubility parameters relevant to supercritical fluids?" Journal of Supercritical Fluids 38(1): 7-12 Martinez, J L (2008) Supercritical Fluid Extraction of Nutraceuticals and Bioactive Compounds, CRC Press Mezzomo, N., J Martínez, et al (2009) "Supercritical fluid extraction of peach (Prunus persica) almond oil: Kinetics, mathematical modeling and scale-up." The Journal of Supercritical Fluids 51(1): 10-16 Mohammad Talebi, A G., Zahra Talebpour, Ali Rassouli, Lila Dolatyari (2004) "Optimization of the extraction of paclitaxel from Taxus baccata L by the use of microwave energy." Journal of Separation science 27(13): 1130-1136 Morita, H., L Wei, et al (1997) "A taxoid from Taxus cuspidata var nana." Phytochemistry 46(3): 583-586 Motonobu Goto, B C R., and Tsutomu Hirose (1996) "Shrinking-Core Leaching Model for SupercriticalFluid Extraction." Journal of Supercritical Fluids 9(1): 128-133 Moura, L S., R N Carvalho Jr., et al (2005) "Supercritical fluid extraction from fennel (Foeniculum vulgare): global yield, composition and kinetic data." The Journal of Supercritical Fluids 35(3): 212-219 8-29 Nagy, B and B Simándi (2008) "Effects of particle size distribution, moisture content, and initial oil content on the supercritical fluid extraction of paprika." The Journal of Supercritical Fluids Selected Papers from the 5th International Symposium in Chemical Engineering and High Pressure Processes, June 24-27, 2007, Segovia, Spain 46(3): 293-298 Owen J Catchpole, M B K (1994) "Measurement and Correlation of binary diffusion coefficients in near critical fluids." Industrial and Engineering Chemistry Research 33(1): 1827 - 1837 Özkal, S G., M E Yener, et al (2005) "Mass transfer modeling of apricot kernel oil extraction with supercritical carbon dioxide." The Journal of Supercritical Fluids 35(2): 119-127 P Swidersky, U H., D Tuma, G.M Schneider, in: G.Brunner, M Perrut (1994) Proceedings of the Third International Symposium on Supercritical Fluids 1: 191 Passos, C P., R M Silva, et al (2009) "Enhancement of the supercritical fluid extraction of grape seed oil by using enzymatically pre-treated seed." The Journal of Supercritical Fluids 48(3): 225-229 Perretti, G M., Luigi; and Fantozzi, Paolo (2006) "Lipid Extraction from Olea Europea L by Supercritical Carbon Dioxide for Analytical Use." International Journal of Food Engineering 2(2) Prasain, J K., P Stefanowicz, et al (2001) "Taxines from the needles of Taxus wallichiana." Phytochemistry 58(8): 1167-1170 Qingyong Lang, C M W (2001) "Supercritical fluid extraction in herbal and natural product studies - a practical review." Talanta 53(1): 771-782 Qui-Cheng Fang, J.-Z Z (1995) "Taxoids from the barks of Taxus wallichiana." Chinese Academy of Medical Sciences and Peking Union Medical College R.W Miller, R G P., C.R.J Smith, E Arnold and J Clardy (1981) "Antileukemic alkaloids from Taxus wallichiana Zucc." Journal of Organic Chemistry 46(1): 1469–1474 Reis-Vasco, E M C., J A P Coelho, et al (2000) "Mathematical modelling and simulation of pennyroyal essential oil supercritical extraction." Chemical Engineering Science 55(15): 2917-2922 Reverchon, E and C Marrone (2001) "Modeling and simulation of the supercritical CO2 extraction of vegetable oils." The Journal of Supercritical Fluids 19(2): 161-175 Richter BE, J B., Ezzel JL, Porter NL, Avdalovic N and Pohl C (1996) "Accelerated solvent extraction: a technique for sample preparation." Analytic Chemistry 68(1): 1033-1039 Robert C.Reid, J M P., Bruce E Poling (1987) The properties of Gases and Liquids, McGrawHill, Inc S., L (1973) Forest botany of China, supplement: 1-2 S.T Chung, K S S (1992) "Multiphase behaviour of binary and ternary systems of heavy aromatic hydrocarbons with supercritical carbon dioxide." Fluid Phase Equilibria 81(1): 321-328 Schwartzberg, H G., Chao, R.Y (1982) "Solute diffusivities in leaching processes." Food Technology 36(1): 73-76 8-30 Senilh, V., Blechert, S., Colin, M., Gue´nard, D., Picot, F., Potier, P., Varenne, P (1984) "Mise en Évidence de Nouveaux Analogues du Taxol Extraits de Taxus baccata." Natural Products 47(1): 131-137 Silva, D C M N., L F V Bresciani, et al (2009) "Supercritical fluid extraction of carqueja (Baccharis trimera) oil: Process parameters and composition profiles." Food and Bioproducts Processing 87(4): 317-326 Simándi B., O M., Lemberkovics É., Kéry Á., Kaszács J., Thyrion F., Mátyás T (1999) "Supercritical Carbon Dioxide Extraction and Fractionation of Oregano Oleoresin." Food Research International 31(1): 723-728 Sovová, H (1994) "Rate of the vegetable oil extraction with supercritical CO2 I Modelling of extraction curves." Chemical Engineering Science 49(3): 409-414 Sovová, H (2005) "Mathematical model for supercritical fluid extraction of natural products and extraction curve evaluation." The Journal of Supercritical Fluids 33(1): 35-52 Sovová, H., J Kucera, et al (1994) "Rate of the vegetable oil extraction with supercritical CO2 II Extraction of grape oil." Chemical Engineering Science 49(3): 415-420 Sovová, H., L Opletal, et al (2007) "Supercritical fluid extraction of lignans and cinnamic acid from Schisandra chinensis." The Journal of Supercritical Fluids 42(1): 88-95 Stahl, E a Q., K.W (1983) "Dense gas extraction on a laboratory scale: A survey of recent results." Fluid Phase Equilibria 8(1): 93-105 Stüber, F., M A Larrayoz, et al (1996) Kinetics of extraction of macroporous solid bodies with a dense gas Process Technology Proceedings High Pressure Chemical Engineering, Proceedings of the 3rd International Symposium on High Pressure Chemical Engineering P R v R a C Trepp, Elsevier: 363-368 Thongprasert, S (1998) "Phase II study of paclitaxel (Taxol®) and ifosfamide (Holoxan®) in inoperable non-small-cell lung cancer." Lung Cancer 19(3): 185-189 V.Rao, K (1995) Method for the isolation and purification of taxol and its natural analogues Vance, N C., R G Kelsey, et al (1994) "Seasonal and tissue variation in taxane concentrations of Taxus brevifolia." Phytochemistry The International Journal of Plant Biochemistry 36(5): 1241-1244 Vandana, V and A S Teja (1997) "The solubility of paclitaxel in supercritical CO2 and N2O." Fluid Phase Equilibria 135(1): 83-87 W., B (1978) Systematics and variability The yew: Taxus baccata L, National Center for Scientific, Technical and Economic Information Service: 149 Wheeler J.R., M M E (1989) "Supercritical fluid extraction and chromatography of representative agricultural products with capillary and microbore columns." Journal of Chromatographic Science 27(9): 534-539 William K Modey, D A M., Mark W Raynor (1997) "Analytical Supercritical Fluid Extraction of Natural Products." Phytochemical Analysis 7(1): 1-15 8-31 Yeo, W., T W T Leung, et al (1998) "A phase II study of combination paclitaxel and carboplatin in advanced nasopharyngeal carcinoma." European Journal of Cancer 34(13): 2027-2031 8-32 CỘNG HÒA XÃ HỘI CHỦ NGHĨA VIỆT NAM Độc Lập – Tự Do – Hạnh Phúc -Họ Tên: Nguyễn Quang Duy Sinh 28 / 01 / 1986 Nam, Bí danh: Chức vụ, đơn vị công tác trước Khi nghiên cứu, thực tập: Cán giảng dạy, LÝ LỊCH KHOA HỌC Dùng cho cán khoa học – kỹ thuật có trình độ đại học, lập theo thông tư số 612/KKT/CB ngày 18-8-1966 Ủy ban Khoa học Kỹ thuật Nhà Nước Đại học Bách Khoa TPHCM Hệ số lương chính: 2.34 Ngành học: Q trình Thiết bị CNHH Chuyên môn: I LÝ LỊCH SƠ LƢỢC : Nguyên quán: Thái Bình Nơi sinh:Bình Phước Địa liên lạc:506/26/5B Lạc Long Quân, Phường 5, Quận 11, TPHCM Dân tộc :Kinh Tôn giáo :Không Thành phần gia đình :Nơng dân Thành phần thân : Ngày vào Đoàn TNCS HCM :26/03/2000 Ngày vào Đảng CSVN : Ngày thức vào Đảng : Chính quyền cao quyền đồn thể qua (nơi, thời gian) : Sức khỏe :Tốt 8-33 II QUÁ TRÌNH ĐÀO TẠO : TRUNG HỌC CHUYÊN NGHIỆP : Chế độ học: Thời gian học: Từ _ / _ / đến _ / _ / Nơi học (trường, thành phố….): Ngành học: ĐẠI HỌC : Chế độ học: Chính quy? Chuyên tu? Tại chức?: Chính quy Thời gian học: Từ 09 / 2004 đến 04 / 2009 Nơi học (trường, thành phố….): Đại học Bách Khoa TPHCM Ngành học: Kỹ thuật Hóa học Tên đồ án, luận án, môn thi tốt nghiệp chủ yếu: Thiết kế hệ thống cung cấp nước nóng cho KTX sử dụng lượng mặt trời Ngày nơi bảo vệ đồ án, luận án, thi tốt nghiệp: Tháng 01/2009 Người hướng dẫn: TS Trần Văn Ngũ TRÊN ĐẠI HỌC: - Thực tập khoa học kỹ thuật từ: / / đến / / (trường, viện, nước): Nội dung thực tập - Cao học từ: 09 / 2009 đến 07 / 2011 (trường, viện, nước): Đại học Bách Khoa Tên luận án: Mơ hình hóa q trình trích ly 10-deaccetylbaccatin III từ thông đỏ sử dụng chất lỏng siêu tới hạn 30 Ngày nơi bảo vệ: 27/05/2011, Đại học Bách Khoa TPHCM Người hướng dẫn: TS Lê Thị Kim Phụng - Nghiên cứu sinh từ: / / _ đến / / _ (trường, viện, nước): Tên luận án: Ngày nơi bảo vệ: Người hướng dẫn: Các môn học bắt buộc chương trình đào tạo sau đại học : Triết học trình độ B: số tiết học: 90 tiết, nơi học: Đại học Bách Khoa TPHCM Lý luận sư phạm đại học: số tiết học: _ tiết, nơi học: Phương pháp luận NCKH: số tiết học: 45 tiết, nơi học: Đại học Bách Khoa TPHCM Tin học: số tiết học: _ tiết, nơi học: Biết ngoại ngữ gì? Trình độ (viết, đọc, nghe, nói; ghi rõ mức độ cụ thể A,B,C…) : Tiếng Anh : Nghe, nói, đọc, viết : Tốt Học vị, học hàm, chức vụ kỹ thuật thức cấp (bằng tốt nghiệp đại học, Kỹ sư, Bác sĩ …., Phó tiến sĩ … Kỹ sư trưởng, Cơng trình sư, Phó giáo sư, Giáo sư ….) ghi rõ ngày, quan cấp tốt nghiệp hay định phong cấp Bằng kỹ sư : Hiệu trưởng trường ĐH Bách Khoa TPHCM cấp ngày 20/03/2009 III HOẠT ĐỘNG KHOA HỌC KỸ THUẬT: 1- Q trình hoạt động khoa học-kỹ thuật, chun mơn Trước sau tốt nghiệp làm làm cơng tác khoa học-kỹ thuật gì? (kỹ thuật, nghiên cứu, thí nghiệm, giảng dạy, quản lý, phục vụ khoa học) 2- Thời gian Tóm tắt q trình hoạt động khoa học – kỹ thuật, nơi công tác 31 07/2009 - Cán giảng dạy, Khoa kỹ thuật Hóa học, ĐH Bách Khoa TPHCM 2- Kết hoạt động khoa học-kỹ thuật: Cơng trình thiết kế, thi cơng, nghiên cứu khoa học kỹ thuật, sáng kiến phát minh, giáo trình giáo án, phương án, tác phẩm … Đã tiến hành hoạt động khoa học-kỹ thuật Ghi rõ nơi, thời gian trước sau tốt nghiệp, độc lập tiến hành hay cộng tác với người khác, tự nhận xét kết tác dụng v.v Nguyen Quang Duy, Phan Dinh Tuan, Le Thi Kim Phung, Supercritical fluid extraction of taxol and 10-deacetylbaccatin III from the leaves of year old taxus wallichiana zucc, Journal of science and technology, Vietnam, 48, 2010 Nguyen Quang Duy, Siti Machmudah, Mitsuru Sasaki, Motonobu Goto, Phung Kim Le, Supercritical fluid extraction of Paclitaxel and 10-Deacetylbaccatin III from Taxus Wallichiana Zucc: multivariate statistical modeling, International Symposium on ChE , Fukuoka, Japan, Dec, 2010 Nguyen Quang Duy, Phan Dinh Tuan, Le Thi Kim Phung,Supercritical fluid extraction of paclitaxel and 10-deacetylbaccatin III from taxus wallichiana zucc: multivariate statistical modelling, 1st International conference in chemical and environmental engineering, Kular Lumpur, Malaysia, Nov, 2010 Nguyen Quang Duy, Phan Dinh Tuan, Le Thi Kim Phung, Mathematical modeling of supercritical fluid extraction of 10-deacetylbaccatin III from cultivated taxus wallichiana zucc, The 3nd Regional Conference on the Interdisiplinary Research on Natural Resources and Materials, Langkawi, Malaysia, Oct, 2010 Nguyen Quang Duy, Phan Dinh Tuan, Le Thi Kim Phung, An alternative taxol resource from year old Taxus Wallichiana Zucc cultivated in dalat, Vietnam,3rd International Student Conference on Advanced Science and Technology (ICAST, Seoul, Korea, Dec, 2009 32 3- Tham dự hội nghị khoa học-kỹ thuật quốc tế (trong nước nước) : tham quan khảo sát, thực tập sản xuất, kỹ thuật… Ở nước (thời gian, nơi, nội dung chuyên môn) - 26/02/2010- 06/03/2010: Tham quan hệ thống Biomass ĐH Tokyo, Nhật Bản - 14/11/2010- 15/12/2010: Thực tập kỹ thuật trích ly sử dụng chất lỏng siêu tới hạn ĐH Kumamoto, Nhật Bản 4- Khen thưởng giải thưởng hoạt động khoa học - kỹ thuật (thời gian, hình thức khen thưởng, quan định) 5- Khả chuyên môn, nguyện vọng hoạt động khoa học-kỹ thuật (ghi cụ thể tỉ mỉ) Tập trung nghiên cứu lĩnh vực mơ hình hóa mơ q trình cơng nghệ hóa học Làm nghiên cứu sinh với đề tài ―Mơ hình hóa q trình tạo hạt tốc độ cao‖ IV HOẠT ĐỘNG CHÍNH TRỊ XÃ HỘI: Tóm tắt q trình tham gia đồn thể quần chúng (thanh niên cộng sản, cơng đồn… ) hội khoa học (hội phổ biến, hội khoa học chuyên ngành… ) phong trào lớn (cải tiến quản lý hợp tác xã,… ) ghi rõ nơi, thời gian Bí thư Đồn Khoa Kỹ thuật Hóa học từ 09/2009 đến tháng 09/2010 XÁC NHẬN CỦA CƠ QUAN HOẶC ĐỊA PHƢƠNG (Thủ Trưởng ký tên đóng dấu) Ngày 07 tháng 07 năm 2011 NGƢỜI KHAI (Họ tên chữ ký) 33 ... of 10-deaccetylbaccatin III from Taxus Wallichiana Zucc) II.NHIỆM VỤ VÀ NỘI DUNG: Tổng quan tài liệu kỹ thuật trích ly xây dựng mơ hình tốn học q trình trích ly sử dụng chất lỏng siêu tới hạn. .. Xây dựng mơ hình tốn học mơ tả đường cong trích ly 10-DAB III từ thơng đỏ sử dụng chất lỏng siêu tới hạn Đánh giá ảnh hưởng thông số công nghệ đến động học trình trích ly 10-DAB III từ thơng đỏ... Bình Phước Chuyên ngành: Quá trình Thiết bị CNHH Mã số : I.TÊN ĐỀ TÀI: MƠ HÌNH HĨA Q TRÌNH TRÍCH LY 10-DEACCETYLBACCATINB III TỪ THƠNG ĐỎ SỬ DỤNG CHẤT LỎNG SIÊU TỚI HẠN (Mathematical modeling