بررسي آزمايشگاهي و مدل سازي سنتز نانو ذرات داروهاي ضد سرطان و آنتي بيوتيك با روش ضد حلال فوق بحراني

چكيده انگليسي :

Experimental Investigation and Modeling of Nanoparticles of Anticancer and Antibiotic Drugs via Supercritical Gas Antisolvent Nadia Esfandiari n esfandiyari@ce iut ac ir Date of Submission 2013 07 20 Department of Chemical Engineering Isfahan University of Technology Isfahan 84156 83111 Iran Degree DOCTOR OF PHILOSOPHY Language Farsi Supervisor S M Ghoreishi ghoreshi@cc iut ac ir Abstract Pharmaceuticals mostly have low solubility in water When the size of pharmaceutical particles are decreased the contact surface and dissolution rate in body are increased Thus their absorption bioavailability is increased and the dosage is decreased The methods of pharmaceutical nanoparticles synthesis via supercritical has attracted interest due to the advantages of controllability of particle size and particle size distribution product and high purity The particle size and particle size distribution could be controlled with varying the operating variables such as pressure temperature initial solute concentration and antisolvent addition rate The supercritical antisolvent method is one of the pharmaceutical nanoparticles synthesis methods via supercritical fluids This method can produce nanoparticles with narrow size distribution and without any solvent residue The purpose of this thesis was the production of nanoparticles ampicillin family of antibiotics and anti cancer 5 Fluorouracil via gas antisolvent process GAS In GAS a solute is dissolved in organic solvent and then supercritical carbon dioxide is added to the solution Each solvent has a particular power to dissolve accordingly the dissolution of carbon dioxide in a solvent decreased the solvent power Therefore the dissolved solute was precipitated via the antisolvent effect of supercritical CO2 The precipitations of particles in gas antisolvent process do not occur at arbitrary operating conditions Thus thermodynamic models are necessary to evaluate the suitable operating conditions in order to obtain the feasible application of GAS process Thermodynamic modeling of these two materials to determine the optimum conditions were investigated The liquid molar volume and mole fraction were determined Thermodynamic modeling of ternary system CO2 DMSO ampicillin indicated that the operation pressure in the GAS experiments must be above 7 3 8 and 8 97 MPa at 308 313 and 319 K respectively The experiments were performed for precipitation of ampicillin and 5 Fluorouracil and investigation of effective variables of precipitation such as antisolvent addition rate pressure temperature and initial solute concentration on particle size and particle size distribution The influence of antisolvent flow rate 1 6 2 and 2 4 mL min temperature 34 40 and 46 solute concentration 20 60 and 100 mg mL and pressure 9 12 and 15 MPa on particle size and particle size distribution were studied The experimental results showed that the mean particle size was decreased with increasing the antisolvent addition rate and pressure In contrast temperature and initial solute concentration had opposite effect on particle size Increasing the temperature and initial solute concentration increased the particle size The material and population balance equations were solved for the determination of kinetic parameters and particle size distribution A combined Crank Nicholson Lax Wendroff method was used to solve the population balance equation Kinetic modeling was performed to determine the nucleation and growth rate parameters via comparison of experimental data and the modeling The validity of the model was investigated by comparison of the model predictions with the experimental data in which the kinetic parameters were optimized The very close compatibility of modeling results with experimental data R2 0 99 indicated that the developed model was successfully capable of predicting the experimental trends in the GAS nanoparticles synthesis When the antisolvent addition rate was increased the nucleation rate was increased and

اسفندياري، ناديا

بررسي آزمايشگاهي و مدل سازي سنتز نانو ذرات داروهاي ضد سرطان و آنتي بيوتيك با روش ضد حلال فوق بحراني

آمپي سيلين , فلوروراسيل , ترموديناميك , سينتيك