FORMULATION AND OPTIMIZATION OF ITRACONAZOLE PRONIOSOMES USING BOX BEHNKEN DESIGN
Keywords:Box behnken design, Proniosomes, Entrapment efficiency (EE), Itraconazole (ITC), Optimization
Objective: The aim of the present study was to obtain an optimized formula of itraconazole (ITC) proniosomes using Box Behnken design.
Methods: Itraconazole proniosomes were prepared using span 60 and/or brij 35 as surfactants, cholesterol and lecithin as a penetration enhancer by slurry method. Various trials have been carried out for investigation of proniosomes. Parameters such as entrapment efficiency (EE%), in vitro drug release, zeta potential, vesicle size and Transmission Electron Microscope were assessed for evaluation of proniosomes.
Results: Entrapment efficiency (EE%) was found to be between 78.56% and 95.46%. The release profile of itraconazole proniosomes occurred in two distinct phases, an initial phase for about 8 h, followed by a slow phase for 16 h. The release pattern shown by these formulations was Higuchi diffusion controlled mechanism. The zeta potential values for all itraconazole proniosomes were in the range of-21.71 to-34.53 mV which confirms their stability. All itraconazoleproniosomes formula was found to be nano-sized and were appeared to be spherical in shape with sharp boundaries. One way analysis of variance (ANOVA) study showed that HLB (X1) had the main effects on most responses (Y).
Conclusion: Box behnken design facilitates optimization of the formulation ingredients on entrapment efficiency, in vitro release of itraconazole proniosomes, zeta potential and vesicle size. Finally, an optimum level of factors was provided by the optimization process.
Cheriyan P, George BJ, Thomas N, Raj P, Samuel J, Carla SrB. Formulation and characterization of maltodextrin based proniosomes of cephalosporins. World J Pharm Sci 2015;3:62-74.
El-Ridy MS, Bawai AA, Safar MM, Mohsen AM. Niosomes as a novel pharmaceutical formulation encapsulating the hepatoprotective drug silymarin. Int J Pharm Pharm Sci 2012;4:549-59.
Naggar VF, Elgamal SS, Allam AN. Proniosomes as a stable carrier for oral acyclovir: Formulation and physicochemical characterization. J Am Sci 2012;8:417-28.
Sammour OA. Improvement of encapsulation efficiency of timolol maleate in liposome by the freeze-thawing method. Zag J Pharm Sci 1992;1:34-42.
Tang J, Wei H, Liu H, Ji H, Dong D, Zhu D, et al. Pharmacokinetics and biodistribution of itraconazole in rats and mice following intravenous administration in a novel liposome formulation. Drug Delivery 2010;17:223-30.
Gareth A. Encyclopedia of pharmaceutical technology. 2nd ed. Marcel Dekker [NY]; 2002.
Tank CJ, Bokhataria C, Baria AH. Formulation and evaluation of aceclofenac loadedmaltodextrin based proniosomes. Int J ChemTech Res 2009;1:567-73.
Sampathi S, Mankala SK, Wankar J, Dodoala. Nanoemulsion based hydrogels of itraconazole for transdermal drug delivery. J Sci Ind Res 2015;74:88-92.
Asija R, Sharma D, Nirmal H. Development of proniosomal gel as a drug carrier for transdermal delivery of acyclovir. J Drug Discovery Ther 2014;2:41-51.
Thomas L, Viswanad V. Formulation and optimization of the clotrimazole-loaded proniosomal gel using 32 factorial design. Sci Pharm 2012;80:731-48.
Box GE, Hunter WG, Hunter JS. Statistics for experiments: design with more than one blocking variable. 2nd ed. [NY]: Wiley Publisher; 1978.
Uchegbu IF, Florence AT. Non-ionic surfactant vesicles (niosomes) physical and pharmaceutical chemistry. Adv Colloid Interface Sci 1995;58:1-55.
Badawi A, El Nabarawi MA, Elrehem RT, Fayed BA. Formulation and evaluation of dispersed permethrinproniosomes in powder and microemulsion-based hydrogel bases for the treatment of scabies. Int J Pharm Pharm Sci 2016;8:221-9.
Alsarra IA. Evaluation of proniosomes as an alternative strategy to optimizepiroxicam transdermal delivery. J Microencapsulation 2008;1:1-7.
Benipal G. Design development and evaluation of proniosomal gel of an antifungal drug ketoconazole. Int J Pharm Sci Rev Res 2015;31:265-72.
Acharya A, Kumar KGB, Ahmed MG, Paudel S. A novel approach to increase the bioavailability of candesartan cilexetil by proniosomal gel formulation: in vitro and in vivo evaluation. Int J Pharm Pharm Sci 2016;8:241-6.
Pardakhty A, Varshosaz J, Rouholamini A. In vitro study of polyoxyethylene alkyl ether niosomes for delivery of insulin. Int J Pharm 2007;328:130-41.
Abdelbary GA, Amin MM, Zakaria MY. Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies. Drug Delivery 2017;24:309â€“19.
Kumar BS, Krishna R, Lakshmi PS, Vasudev DT, Nair SC. Formulation and evaluation of niosomal suspension of cefixime. Asian J Pharm Clin Res 2017;10:194-201.
Pankaj S, Rini T, Dandagi PM. Formulation and evaluation of proniosome based drug delivery system of the antifungal drug clotrimazole. Int J Pharm Sci Nanotech 2013;6:1945-51.
Arafa MG, Ayoub BM. Nano-vesicles of salbutamol sulphate in metered dose inhalers: formulation, characterization and in vitro evaluation. Int J Appl Pharm 2017;9:100-5.
Singla S, Harikumar SL, Aggarwal G. Proniosomes for penetration enhancement in transdermal system. Int J Drug Devand Res 2012;4:1-13.
Kamboj S, Saini V, Bala S. Formulation and characterization of drug loaded nonionic surfactant vesicles (niosomes) for oral bioavailability enhancement. Sci World J 2014:1-8. http://dx.doi.org/10.1155/2014/959741
Okare VC, Attama AA, Ofokansi KC, Esimone CO, Onuigbo EB. Formulation and evaluation of niosomes. Indian J Pharm Sci 2011;73:323-8.
Chauhan MK, Sahoo PK, Rawat AS, Dugga LD, Kandwal M, Nidhi S. Formulation, characterization and in vitro evaluation of tactically engineered proniosomes for successful oral delivery of ramipril. Pharm Lett 2015;7:93-7.
Balakrishnan P, Shanmugam S, Lee WM, Kim JO, Oh DH, Kim DD, et al. Formulation and in vitro assessment of minoxidilniosomes for enhanced skin delivery. Int J Pharm 2009;10:1004-20.
Desai S, Doke A, Disouza J, Athawale R. Development and evaluation of antifungal topical niosomal gel formulation. Int J Pharm Pharm Sci 2011;3:224-31.
Ola AMM, El-Ashmoony MM, Elgazayerly ON. Niosome-encapsulated clomipramine for transdermal controlled delivery. Int J Pharm Pharm Sci 2014;6:567-75.
Mishra A, Kapoor A, Bhargava. A proniosomal gel as a carrier for transdermal drug delivery of clotrimazole. Int J Pharm Pharm Sci 2012;4 Suppl 4:610-4.
Das MK, Palei NN. Sorbitan ester niosomes for topical delivery of rofecoxib. Indian J Exp Biol 2011;49:438-45.