Optimization of polylactic-co-glycolic acid nanoparticles containing itraconazole using 23 factorial design

AAPS PharmSciTech - 2003
Mukdavan Prakobvaitayakit1, Ubonthip Nimmannit1
1Department of Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand

Tóm tắt

This study investigated the utility of a 23 factorial design and optimization process for polylactic-co-glycolic acid (PLGA) nanoparticles containing itraconazole with 5 replicates at the center of the design. Nanoparticles were prepared by solvent displacement technique with PLGAX 1 (10, 100 mg/mL), benzyl benzoateX 2 (5, 20 μg/mL), and itraconazoleX 3 (200, 1800 μg/mL). Particle size (Y 1), the amount of itraconazole entrapped in the nanoparticles (Y 2), and encapsulation efficiency (Y 3) were used as responses. A validated statistical model having significant coefficient figures (P<.001) for the particle size (Y 1), the amount of itraconazole entrapped in the nanoparticles (Y 2), and encapsulation efficiency (Y 3) as function of the PLGA (X 1), benzyl benzoate (X 2), and itraconazole (X 3) were developed: Y1=373.75+66.54X1+52.09X2+105.06X3−4.73X1X2+46.30X1X3; Y2=472.93+73.45X1+ 169.06X2+333.03X3+62.40X1X3+141.49X2X3; Y3= 57.36+6.53X1+15.52X2−12.59X3+1.01X1X3+ 1.73X2X3.X 1,X 2, andX 3 had a significant effect (P<.001) onY 1,Y 2, andY 3. The particle size, the amount of itraconazole entrapped in the nanoparticles, and the encapsulation efficiency of the 4 formulas were in agreement with the predictions obtained from the models (P<.05). An overlay plot for the 3 responses shows the boundary in whichY 1 shows the boundary in which a number of combinations of concentration of PLGA, benzyl benzoate, and itraconazole will result in a satisfactory process. Using the desirability approach with the same constraints, the solution composition having the highest overall desirability (D=0.769) was 10 mg/mL of PLGA, 16.94 μg/mL of benzyl benzoate, and 1001.01 μg/mL of itraconazole. This approach allowed the selection of the optimum formulation ingredients for PLGA nanoparticles containing itraconazole of 500 μg/mL.

Từ khóa


Tài liệu tham khảo

Allemann E, Leroux RG. Biodegradable nanoparticles of particles of poly(lactic acid) and poly(lactic-co-glycolic acid) for parenteral administration. In: Gregoridas G, ed.Pharmaceutical Dosage Form. New York, NY: Marcel Dekker, 1999:163–186.

Wise DL, Fellmann TD, Sanderson JE, Wentworth RL. Lactic /glycolic acid polymers. In: Gregoridas G, ed.Drug Carriers in Biology and Medicine. London, UK: Academic Press; 1979:237–270.

Fessi H, Puisieux F, Devissagnet JP, Ammoury N, Betina S. Nanocapsule formation by interfacial deposition following solvent displacement.Int J Pharm. 1989;55:R1-R4.

Cauchetier E, Deniau M, Fessi H, Astier A, Paul A. Atovaquone-loaded nanocapsules: influence of the polymer on their in vitro characteristics.Int J Pharm. 2003;250:273–281.

Barichello JM, Morishita M, Takayama K, Nagai T. Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method.Drug Dev Ind Pharm. 1999;25(4):471–476.

Fawaz F, Bonini F, Guyot M, Lagueny AM, Fessi H, Devissaguet JP. Influence of poly(DL-lactide) nanocapsules on the biliary clearance and enterohepatic circulation of indomethacin in the rabbit.Pharm Res. 1993;10:750–756.

Chasteigner DS, Fessi H, Devissaguet JP, Puisieux F. Comparative study of the association of itraconazole with colloidal drug carriers.Drug Dev Res. 1996;38:125–133.

Heykants J, Peer V, van de Velde V, Rooy PV, Meuldermans W, Lavrijsen K, Woestenborghs R, Van Cutsem J, Cauwenbergh G. The clinical pharmacokinetics of itraconazole: an overview.Mycoses. 1989;32(suppl. 1):67–68.

Stetsko G. Statistical experimental design and its application to pharmaceutical development problems.Drug Dev Ind Pharm. 1986;12:1109–1123.

Dawoodbhai S, Suryanarayan ER, Woodruff CW, Rhodes CT. Optimization of tablet formulations containing talc.Drug Dev Ind Pharm. 1991;17(10):1343–1371.

Bos CE, Bolhuis GK, Lerk CF. Optimization of tablet formulations based on starch/lactose granulations for use in tropical countries.Drug Dev Ind Pharm. 1991;17(17):2373–2389.

Ceschel GC, Maffei P, Badiello R. Optimization of hydrochlorothiazide tablets.Drug Dev Ind Pharm. 1999;25(11):1167–1176.

Zaghloul AA, Vaithiyalingam SR, Faltinek J, Reddy IK, Khan MA. Response surface methodology to obtain naproxen controlled release tablets from its microspheres with Eudragit L 100-55.J Microencapsul. 2001;18(5):651–662.

Arica B, Kas HS, Orman MN, Hincal AA. Biodegradable bromocryptine mesylate microspheres prepared by a solvent evaporation technique. I. Evaluation of formulation variables on microspheres characteristics for brain delivery.J Microencapsul. 2002;19(4):473–484.

Adinarayana K, Ellaiah P. Response surface optimization of the critical medium components for the production of alkaline protease by a newly isolatedBacillus sp.J Pharm Pharm Sci. [electronic resource]. 2002;5(3):272–278. Available at: http://www.ualberta.ca/~csps. Accessed January 15, 2003.

Nangia A, Lam F, Hung CT. Formulation optimization of a hydrocolloid dressing.Drug Dev Ind Pharm. 1990;16(14):2109–2123.

Elkheshen SA, Badawi SS, Badawi AA. Optimization of a reconstitutable suspension of rifampicin using 24 factorial design.Drug Dev Ind Pharm. 1996;22(7):623–630.

Montgomery DC, ed.Design and Analysis of Experiments. 5th ed. New York, NY: Wiley & Sons; 2001.

Law D, Moore CB, Denning DW. Bioassay for serum itraconazole concentrations using hydroxyitraconazole standars.Antimicrob Agents Chemother. 1994;38:1561–1566.

Akhnazarova S, Kafaro V, eds.Experiment Optimization in Chemistry and Chemical Engineering. Moscow, Russia: Mir House Publications; 1982.

Box GEP, Hunter WG, Hunter JS, eds.Statistic for Experiments. New York, NY: John Wiley and Sons; 1978.

Box GEP, Wilson KB. On the experimental attainment of optimum conditions.J Roy Stat Soc B. 1951;B13:1–45.

Thông tin
Thông tin xuất bản

AAPS PharmSciTech

Thông tin tác giả