INVESTIGATION AND OPTIMIZATION OF FORMULATION PARAMETERS FOR SELFNANOEMULSIFYING DELIVERY SYSTEM OF TWO LIPOPHILIC AND GASTROINTESTINAL LABILE DRUGS USING BOX-BEHNKEN DESIGN
Keywords:Curcumin, Duloxetine hydrochloride, Binary mixture, Curcumin - duloxetine hydrochloride - self-nanoemulsifying drug delivery systems, Box Behnken design, Castor oil, Nil, Tween-80
Objective: Present research work aims toward codelivery of two hydrophobic drugs, curcumin (CRM) and duloxetine hydrochloride (DXH) through self-nanoemulsifying drug delivery systems (SNEDDS).
Methods: Initially, binary mixture in the ratio of 1:1 was prepared and then loaded into SNEDDS. Box-Behnken design (BBD) was adopted to develop SNEDDS. As per the optimal design, 13 SNEDDS prototypes were prepared. Castor oil, tween-80 and Transcutol PÂ® were used as oil, surfactant, and cosurfactant, respectively. To 1 mL of SNEDDS, 30 mg each of CRM and DXH was loaded (CRM-DXH- SNEDDS).
Results: The design revealed that for mean droplet size, polydispersity index (PDI), as well as percentage drug loading, all the three factors, i.e. ratio of oil (a), surfactant (b), and cosurfactant (c) were found to give significant effect. Factor B showed the most significant effect on mean droplet size (y1). In case of PDI (y2), factors B and C exerted maximum influence, whereas, Factor A has shown non-significant effect. For percentage drug loading of drugs (y3 and y4), all the three factors were found to have the most significant effect. The optimized batch of CRM-DXH- SNEDDS having composition castor oil, tween-80, and Transcutol PÂ® in the ratio: 2.17:5.22:2.61, revealed that the mean drug loading (%) of CRM and DXH in an optimized batch of SNEDDS was found to be 87.22Â±1.87 and 92.32Â±0.19%, respectively. The mean droplet size, PDI, and zeta potential of formed SNEDDS were observed as 113.14Â±1.14 nm, 0.20Â±0.026, and âˆ’13.2 mV, respectively.
Conclusion: BBD provided optimal formula composition for SNEDDS for obtaining desirable drug loading, emulsion droplet size, and zeta potential.
Finnerup NB, Otto M, McQuay H, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: An evidence based proposal. Pain 2005;118:289-305.
Kuhad A, Bishnoi M, Chopra K. Anti-nociceptive effect of duloxetine in mouse model of diabetic neuropathic pain. Indian J Exp Biol 2009;47:193-7.
Xu B, Descalzi G, Ye HR, Zhuo M, Wang YW. Translational investigation and treatment of neuropathic pain. Mol Pain 2012;8:15.
Katsuyama S, Aso H, Otowa A, Yagi T, Kishikawa Y, Komatsu T, et al. Antinociceptive effects of the serotonin and noradrenaline reuptake inhibitors milnacipran and duloxetine on vincristine-induced neuropathic pain model in mice. ISRN Pain 2014;2014:915464.
Mannari C, Origlia N, Scatena A, Del Debbio A, Catena M, Dellâ€™Agnello G, et al. BDNF level in the rat prefrontal cortex increases following chronic but not acute treatment with duloxetine, a dual acting inhibitor of noradrenaline and serotonin re-uptake. Cell Mol Neurobiol 2008;28:457-68.
Geetha RV, Gokul G. Effect of Curcuma longa extract on biofilm formation by Streptococcus mutans. Asian J Pharm Clin Res 2017;2:186-7.
Jeon Y, Kim CE, Jung D, Kwak K, Park S, Lim D, et al. Curcumin could prevent the development of chronic neuropathic pain in rats with peripheral nerve injury. Curr Ther Res 2013;74:1-4.
Vyas A, Dandawate P, Padhye S, Ahmad A, Sarkar F. Perspectives on new synthetic curcumin analogs and their potential anticancer properties. Curr Pharm Des 2013;19:2047-69.
Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 2009;41:40-59.
Zhao X, Xu Y, Zhao Q, Chen CR, Liu AM, Huang ZL. Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain: Descending monoamine system and opioid receptors are differentially involved. Neuropharmacology 2012;62:843-54.
Jain K, Sood S, Gowthamarajan K. Modulation of cerebral malaria by curcumin as an adjunctive therapy. Braz J Infect Dis 2013;17:579-91.
MendonÃ§a LM, da Silva Machado C, Teixeira CC, de Freitas LA, Bianchi MD, Antunes LM. Curcumin reduces cisplatin-induced neurotoxicity in NGF-differentiated PC12 cells. Neurotoxicology 2013;34:205-11.
Abbas SH, Abdulridha MK, Najeb AA. Potential benefit of curcumin adjuvant therapy to the standard helicobacter pylori eradication therapy in patients with peptic ulcer disease. Asian J Pharm Clin Res 2017;10:313-7.
Srinivasan M. Curcumin, a potent anticarcinogenic polyphenol - A review. Asian J Pharm Clin Res 2014;7:1-8.
Mohanty C, Das M, Sahoo SK. Emerging role of nanocarriers to increase the solubility and bioavailability of curcumin. Expert Opin Drug Deliv 2012;9:1347-64.
Patel K, Padhye S, Nagarsenker M. Duloxetine HCl lipid nanoparticles: Preparation, characterization, and dosage form design. AAPS PharmSciTech 2012;13:125-33.
Young NA, Bruss MS, Gardner M, Willis WL, Mo X, Valiente GR, et al. Oral administration of nano-emulsion curcumin in mice suppresses inflammatory-induced NFÎºB signaling and macrophage migration. PLoS One 2014;9:e111559.
Ray B, Bisht S, Maitra A, Maitra A, Lahiri DK. Neuroprotective and neurorescue effects of a novel polymeric nanoparticle formulation of curcumin (NanoCurcâ„¢) in the neuronal cell culture and animal model: Implications for Alzheimerâ€™s disease. J Alzheimerâ€™s Dis 2011;23:61-77.
Setia A, Kansal S, Goyal N. Development and optimization of enteric coated mucoadhesive microspheres of duloxetine hydrochloride using 32 full factorial design. Int J Pharm Invest 2013;3:141.
Shah R, Zidan A, Funck T, Tawakkul M, Nguyenpho A, Khan M. Quality by design: Characterization of self-nano-emulsified drug delivery systems (SNEDDs) using ultrasonic resonator technology. Int J Pharm 2007;341:189-94.
Sheladia S, Patel B. Implementation of QBD approach to develop and validate analytical method for simultaneous estimation of duloxetine hydrochloride and methylcobalamin in pharmaceutical dosage form by HPTLC method. Int J Pharm Pharm Sci 2016;9:105-13.
Khan AA, Mudassir J, Mohtar N, Darwis Y. Advanced drug delivery to the lymphatic system: Lipid-based nanoformulations. Int J Nanomed 2013;8:2733.
Mohanraj V, Chen Y. Nanoparticles-a review. Trop J Pharm Res 2006;5:561-73.
Kang JH, Oh DH, Oh YK, Yong CS, Choi HG. Effects of solid carriers on the crystalline properties, dissolution and bioavailability of flurbiprofen in solid self-nanoemulsifying drug delivery system (solid SNEDDS). Eur J Pharm Biopharm 2012;80:289-97.
Date AA, Nagarsenker M. Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil. Int J Pharm 2007;329:166-72.
Desai N, Nagarsenker M. Design and evaluation of self-nanoemulsifying pellets of repaglinide. AAPS PharmSciTech 2013;14:994-1003.
Kumar B, Garg V, Singh S, Pandey NK, Bhatia A, Prakash T, et al. Impact of spray drying over conventional surface adsorption technique for improvement in micromeritic and biopharmaceutical characteristics of self-nanoemulsifying powder loaded with two lipophilic as well as gastrointestinal labile drugs. Powder Technol 2017;326:425-42.
Kumar B, Malik AH, Sharma P, Rathee H, Prakash T, Bhatia A, et al. Validated reversed-phase high-performance liquid chromatography method for simultaneous estimation of curcumin and duloxetine hydrochloride in tablet and self-nanoemulsifying drug delivery systems. J Pharm Res 2017;11:1166.
Sood S, Jain K, Gowthamarajan K. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment. Colloid Surfaces B Biointerfaces 2014;113:330-7.
Shah VP, Tsong Y, Sathe P, Liu JP. In vitro dissolution profile comparison - Statistics and analysis of the similarity factor, f2. Pharm Res 1998;15:889-96.
Singare DS, Marella S, Gowthamrajan K, Kulkarni GT, Vooturi R, Rao PS, et al. Optimization of formulation and process variable of nanosuspension: An industrial perspective. Int J Pharm 2010;402:213-20.
How to Cite
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.