STATISTICAL OPTIMIZATION AND STABILITY STUDY OF QUERCETIN-LOADED MICROEMULSION
Keywords:Quercetin, Microemulsion, Antioxidative, Anti-tyrosinase
Objective: This research aims to develop a quercetin microemulsion system to improve the solubility of quercetin and to study the stability of the microemulsions.
Methods: The microemulsion is prepared by water titration method using isopropyl myristate (oil), Tween 60®/Span 80® (3:2) (surfactant) and ethanol (co-surfactant). Two different aqueous phases, water or NaCl solution, were used to prepare microemulsions and the influence of each parameter was described. DPPH scavenging and anti-tyrosinase activity were performed along with chemical stability to evaluate the functional stability of microemulsions.
Results: The influence of percentage of oil phase (variable A) on the solubility of quercetin was less significant than that of percentage of surfactant/co-surfactant (variable B). Compared to those prepared with water (variable C), the solubility of quercetin in microemulsions prepared with NaCl solution significantly increased. The ratio of the high level to low level for solubility of three variables was 1.135, 1.315 and 1.591 respectively. Increasing variable A and B led to an increase in the particle size of microemulsions from 120.08 nm to 188.38 nm and 48.18 nm to 260.28 nm, respectively. The influence of variable B was quite significant, while variable C has no significant effect on particle size. Quercetin microemulsions showed good chemical and functional stability when stored at 4 °C. Under other conditions, especially at 40 °C, the activity of the microemulsion is considerably reduced.
Conclusion: The influence of different variables on the characteristics of microemulsions was complicated. Care must be taken in the composition and storage conditions of these formulations.
Vicentini FT, Fonseca YM, Pitol DL, Iyomasa MM, Bentley MV, Fonseca MJ. Evaluation of the protective effect of a water-in-oil microemulsion incorporating quercetin against UVB-induced damage in hairless mice skin. J Pharm Pharm Sci 2008;13:274-85.
Svobodova A, Psotova J, Walterova D. Natural phenolics in the prevention of UV-induced skin damage. A review. Biomed Papers 2003;147:137-45.
Casagrande R, Georgetti SR, Verri WA Jr, Dorta DJ, dos Santos AC, Fonseca MJ. Protective effect of topical formulations containing quercetin against UVB-induced oxidative stress in hairless mice. J Photochem Photobiol B 2006;84:21-7.
Pinnell SR. Cutaneous photodamage, oxidative stress, and topical antioxidant protection. J Am Acad Dermatol 2003;48:1-19.
Maia Campos PM, Fianeti MD, Kanashiro A, Lucisano Valim YM, Gaspar LR. In vitro antioxidant and in vivo photoprotective effects of an association of bioflavonoids with liposoluble vitamins. Photochem Photoviol 2006;82:683-8.
Ruiz PA, Braune A, Holzlwimmer G, Quintanilla Fend L, Haller D. Quercetin inhibits TNF-α induced NF-κB transcription factor recruitment to proinflammatory gene promoters in murine intestinal epithelial cells. J Nutr 2007;137:1208-15.
Mythili T, Ravindhran R. Phytochemical screening and antimicrobial activity of Sesbania sesban (L.) merr. Asian J Pharm Clin Res 2012;5:179-82.
Choquenet B, Couteau C, Paparis E, Coiffard LJM. Quercetin and rutin as potential sunscreen agents: determination of efficacy by an in vitro method. J Nat Prod 2008;71:1117-8.
Lu B, Huang Y, Chen Z, Ye J, Xu H, Chen W, et al. Niosomal nanocarriers for enhanced skin delivery of quercetin with functions of anti-tyrosinase and antioxidant. Molecules 2019;24:2322-38.
Cho S. The role of functional foods in cutaneous anti-aging. J Lifestyle Med 2014;4:8-16.
Priprem A, Watanatorn J, Sutthiparinyanont S, Phachonpai W, Muchimapura S. Anxiety and cognitive effects of quercetin liposomes in rats. Nanomedicine 2008;4:70-8.
Jee JP, Pangeni R, Jha SK, Byun Y, Park JW. Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy. Int J Nanomed 2019;14:5449-75.
Sun M, Gao Y, Pei Y, Guo C, Li H, Cao F, et al. Development of nanosuspension formulation for oral delivery of quercetin. J Biomed Nanotechnol 2010;6:325-32.
Hamed R, Basil M, AlBaraghthi T, Sunoqrot S, Tarawneh O. Nanoemulsion-based gel formulation of diclofenac diethylamine: design, optimization, rheological behavior and in vitro diffusion studies. Pharm Dev Technol 2016;21:980-9.
Landi Librandi AP, Chrysostomo TN, Caleiro Seixas Azzolini AE, Marzocchi-Machado CM, de Oliveira CA, Lucisano-Valim YM. Study of quercetin loaded liposomes as potential drug carriers: in vitro evaluation of human complement activation. J Liposome Res 2012;22:89-99.
Bose S, Michniak Kohn B. Preparation and characterization of lipid-based nanosystems for topical delivery of quercetin. Eur J Pharm Sci 2013;48:442-52.
Kajbafvala A, Salabat A, Salimi A. Formulation, characterization and in vitro/ex-vivo evaluation of quercetin-loaded microemulsion for topical application. Pharma Dev Technol 2018;23:741-50.
Huang YB, Lee KF, Huang CT, Tsai YH, Wu PC. The effect of component of cream for topical delivery of hesperetin. Chem Pharm Bull 2010;58:611-4.
Thorat YS, Kote NS, Patil VV, Hosmani AH. Formulation and evaluation of microemulsion containing neem seed oil. Int J Curr Pharm Res 2020;12:31-6.
Verri WA Jr, Cunha TM, Parada CA, Poole S, Cunha FQ, Ferreira SH. Hypernociceptive role of cytokines and chemokines: targets for analgesic drug development. Pharmacol Ther 2006;112:116-38.
Gupta S, Moulik SP. Biocompatible microemulsions and their prospective uses in drug delivery. J Pharm Sci 2008;97:22-45.
Vandervoort J, Ludwig A. Biocompatible stabilizers in the preparation of PLGA nanoparticles: a factorial design study. Int J Pharm 2002;238:77-92.
Chang LC, Wu CL, Liu CW, Chuo WH, Li PC, Tsai TR. Preparation, characterization and cytotoxicity evaluation of tanshinone IIA nanoemulsions. J Biomed Nanotechnol 2011;7:1-10.
Srinivas D, Sagar VS. Enhancing the bioavailability of simvastatin using microemulsion drug delivery system. Asian J Pharm Clin Res 2012;5:134-9.
Chowdary KPR, Shankar KR, Sowjanya VVLSP. Optimization of irvesartan tablet formulation by 23 factorial design. Int J Curr Pharm Res 2015;7:39-42.
Yadav V, Jadhav P, Kanase K, Bodhe A, Dombe S. Preparation and evaluation of microemulsion containing an antihypertensive drug. Int J Appl Pharm 2018;10:138-46.
Lv X, Liu T, Ma H, Tian Y, Li L, Li Z, et al. Preparation of essential oil-based microemulsions for improving the solubility, pH stability, photostability, and skin permeation of quercetin. AAPS PharmSciTech 2017;18:3097-104.
Goddeeris C, Cuppo F, Reynaers H, Bouwman WG, Van den Mooter G. Light-scattering measurements on microemulsions: Estimation of droplet sizes. Int J Pharm 2006;312:187-95.
Higuchi T. Mechanism of sustained-release medication: theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci 1963;52:1145-9.
Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13:123-33.
Vicentini FT, Casagrande R, Verri WA Jr, Georgetti SR, Bentley MV, Fonseca MJ. Quercetin in lyotropic liquid crystalline formulations: physical, chemical and functional stability. AAPS PharmSciTech 2008;9:591-6.
Fenglin H, Ruili L, Bao H, Liang M. Free radical scavenging activity of extracts prepared from fresh leaves of selected Chinese medicinal plants. Fitoterapia 2004;75:14-23.
Brand Williams W, Cuvelier ME, Berset C. Use of a free radical method to evaluate antioxidant activity. LWT Food Sci Technol 1995;28:25-30.
Kobayashi Y, Kayahara H, Tadasa K, Nakamura T, Tanaka H. Synthesis of amino acid derivatives of kojic acid and their tyrosinase inhibitory activity. Biosci Biotechnol Biochem 1995;59:1745-6.
Kitagawa S, Yoshii K, Morita SY, Teraoka R. Efficient topical delivery of chlorogenic acid by an oil-in-water microemulsion to protect skin against UV-induced damage. Chem Pharm Bull 2011;59:793-6.
Sintov AC, Shapiro L. New microemulsion vehicle facilitates percutaneous penetration in vitro and cutaneous drug bioavailability in vivo. J Controlled Release 2004;95:173-83.
Vicentini FT, Vaz MM, Fonseca YM, Bentley MV, Fonseca MJ. Characterization and stability study of a water-in-oil microemulsion incorporating quercetin. Drug Dev Ind Pharm 2011;37:47-55.
Lee GH, Lee SJ, Jeong SW, Kim HC, Park G, Lee SG, et al. Antioxidative and antiinflammatory activities of quercetin-loaded silica nanoparticles. Colloids Surf B 2016;143:511-7.
Chen H, Chang X, Du D, Li J, Xu H, Yang X. Microemulsion based hydrogel formulation of ibuprofen for topical delivery, Int J Pharm 2006;315:52-8.
Vicentini FT, Simi TR, Del Ciampo JO, Wolga NO, Pitol DL, Lyomasa MM, et al. Quercetin in w/o microemulsion: in vitro and in vivo skin penetration and efficacy against UVB-induced skin damages evaluated in vivo. Eur J Pharm Biopharm 2008;69:948-57.
Qian ZJ, Jung WK, Kim SK. Free radical scavenging activity of a novel antioxidative peptide purified from hydrolysate of bullfrog skin, rana catesbeiana shaw. Bioresour Technol 2008;99:1690-8.