BOX-BEHNKEN DESIGN OPTIMIZATION OF SALICYLIC ACID LOADED LIPOSOMAL GEL FORMULATION FOR TREATMENT OF FOOT CORN

SHUBHRIKA CHANDWANI; T. R. SAINI; REENA SONI; SURESH K. PASWAN; PRAKASH K. SONI

doi:10.22159/ijap.2023v15i3.47455

Authors

SHUBHRIKA CHANDWANI Nanotechnology Research Lab, Department of Pharmacy, Shri G. S. Institute of Technology and Science, Indore 452003, (M. P.), India
T. R. SAINI Nanotechnology Research Lab, Department of Pharmacy, Shri G. S. Institute of Technology and Science, Indore 452003, (M. P.), India
REENA SONI Nanotechnology Research Lab, Department of Pharmacy, Shri G. S. Institute of Technology and Science, Indore 452003, (M. P.), India
SURESH K. PASWAN Nanotechnology Research Lab, Department of Pharmacy, Shri G. S. Institute of Technology and Science, Indore 452003, (M. P.), India https://orcid.org/0000-0002-0030-0914
PRAKASH K. SONI Nanotechnology Research Lab, Department of Pharmacy, Shri G. S. Institute of Technology and Science, Indore 452003, (M. P.), India https://orcid.org/0000-0002-2202-3778

DOI:

https://doi.org/10.22159/ijap.2023v15i3.47455

Keywords:

Salicylic acid, Liposomes, Box-Behnken design, Liposomal gel, Topical drug delivery, Foot corn, Design of experiment, Optimization

Abstract

Objective: The present research is aimed to design and optimize a liposomal gel formulation of salicylic acid (SA) for enhanced drug permeation, higher skin drug retention, sustained release drug delivery and reduced side effects in the effective treatment of foot corn.

Methods: Formulation designing and optimization of SA-loaded liposomes was done by box-Behnken experimental design using the three-factor, three-level approach. Phospholipid content, cholesterol content and drug content were selected as independent variables; while the critical quality attributes (CQAs) of liposomal formulation like particle size, PDI, zeta potential, entrapment efficiency and cumulative % drug release were considered as response variables. The SA-loaded liposomes were prepared by ethanol injection method and were characterized for desired CQAs. Finally, topical gel formulation of SA-loaded liposomes was developed and evaluated for drug content, homogeneity, spreadability, in vitro drug release, drug release kinetics, ex-vivo drug permeation and skin retention properties.

Results: The particle size, PDI, zeta potential, entrapment efficiency and cumulative % drug release of SA-loaded liposomes was found to be 261.2 nm, 0.28, 0.7 mV, 57.53% and 99.57%, respectively. Developed topical gel formulation of SA-loaded liposomes exhibited a sustained drug release profile (64.48% cumulative release over 360 min) following Higuchi model kinetics. The developed formulation showed almost 2-fold enhanced drug permeation (i.e., 26.50%) and more than 2-fold higher drug retention (i.e., 10.90%) on porcine ear skin as compared to the plain salicylic acid gel.

Conclusion: The SA-loaded liposomes and developed topical gel formulation possessed all desired CQAs. The in vitro drug release kinetics, ex-vivo drug permeation and skin retention studies confirmed the suitability of the developed formulation for topical application in the effective treatment of foot corn.

Downloads

Download data is not yet available.

References

Silfverskiold JP. Common foot problems. Relieving the pain of bunions, keratoses, corns, and calluses. Postgrad Med. 1991;89(5):183-8. doi: 10.1080/00325481.1991.11700901, PMID 1826149.

Singh D, Bentley G, Trevino SG. Callosities, corns, and calluses. BMJ. 1996;312(7043):1403-6. doi: 10.1136/bmj.312.7043.1403a, PMID 8646101.

Redmond A, Allen N, Vernon W. Effect of scalpel debridement on the pain associated with plantar hyperkeratosis. J Am Podiatr Med Assoc. 1999;89(10):515-9.

Madan RK, Levitt J. A review of toxicity from topical salicylic acid preparations. J Am Acad Dermatol. 2014;70(4):788-92.

Princely S, Dhanaraju M. Design, formulation and characterization of liposomal-encapsulated gel for transdermal delivery of fluconazole. Asian J Pharm Clin Res. 2018;11(8):417-24.

Antimisiaris SG, Marazioti A, Kannavou M, Natsaridis E, Gkartziou F, Kogkos G. Overcoming barriers by local drug delivery with liposomes. Adv Drug Deliv Rev. 2021;174:53-86. doi: 10.1016/j.addr.2021.01.019, PMID 33539852.

Shahi S, Sonwane U, Zadbuke N, Tadwee I. Design and development of diphenhydramine hydrochloride topical liposomal drug delivery system. Int J Pharm Pharm Sci. 2013;5:534-42.

Shabnam SP, Babu R. Formulation and evaluation of parenteral methotraxate nanoliposomes. Int J Pharm Pharm Sci. 2014;6(11):295-300.

Bhalerao SS, Raje Harshal A. Preparation, optimization, characterization, and stability studies of salicylic acid liposomes. Drug Dev Ind Pharm. 2003;29(4):451-67. doi: 10.1081/ddc-120018380, PMID 12737538.

Wasankar SR, Faizi SM, Deshmuk AD. Formulation and development of liposomal gel for topical drug delivery system. Int J Pharm Sci Res. 2012;3(11):27-38.

Patel VB, Misra A, Marfatia YS. Topical liposomal gel of tretinoin for the treatment of acne: research and clinical implications. Pharm Dev Technol. 2000;5(4):455-64. doi: 10.1081/pdt-100102029, PMID 11109245.

Swami H, Bilandi A, Kataria M, Kaur K. Formulation and evaluation of liposomal gel of lornoxicam. World J Pharm Res. 2015;4990:2312-38.

Arpna I, Ahmed Masheer K. Box-behnken design for optimization of formulation variables for controlled release gastroretentive tablet of verapamil hydrochloride. Int J App Pharm. 2023;15(1):256-63. doi: 10.22159/ijap.2023v15i1.46489.

Ferreira SLC, Bruns RE, Ferreira HS, Matos GD, David JM, Brandao GC. Box-Behnken design: an alternative for the optimization of analytical methods. Anal Chim Acta. 2007;597(2):179-86. doi: 10.1016/j.aca.2007.07.011, PMID 17683728.

Chaudhary H, Kohli K, Amin S, Rathee P, Kumar V. Optimization and formulation design of gels of diclofenac and curcumin for transdermal drug delivery by box-Behnken statistical design. J Pharm Sci. 2011;100(2):580-93. doi: 10.1002/jps.22292, PMID 20669331.

Kesharwani PS, Alhakamy NA, Hosny KM, Haque A. QbD enabled azacitidine loaded liposomal nanoformulation and its in vitro evaluation. Polymers (Basel). 2021;13(2).

Vemuri S, Rhodes CT. Preparation and characterization of liposomes as therapeutic delivery systems: a review. Pharm Acta Helv. 1995;70(2):95-111. doi: 10.1016/0031-6865(95)00010-7, PMID 7651973.

Gupta A, Singh S, Kotla NG, Webster TJ. Formulation and evaluation of a topical niosomal gel containing a combination of benzoyl peroxide and tretinoin for antiacne activity. Int J Nanomedicine. 2015;10:171-82.

Soni PK, Saini TR. Purification of drug-loaded liposomal formulations by a novel stirred cell ultrafiltration technique. Pharm Nanotechnol. 2021;9(5):347-60. doi: 10.2174/2211738509666211124145848, PMID 34819014.

Soni PK, Saini TR. Formulation design and optimization of cationic-charged liposomes of brimonidine tartrate for effective ocular drug delivery by design of experiment (DoE) approach. Drug Dev Ind Pharm. 2021;47(11):1847-66. doi: 10.1080/03639045.2022.2070198, PMID 35484943.

Gill P, Moghadam TT, Ranjbar B. Differential scanning calorimetry techniques: applications in biology and nanoscience. J Biomol Tech. 2010;21(4):167-93. PMID 21119929.

Biltonen RL, Lichtenberg D. The use of differential scanning calorimetry as a tool to characterize liposome preparations. Chem Phys Lipids. 1993;64(1):129-42.

Fathalla D, Youssef EMK, Soliman GM. Liposomal and ethosomal gels for the topical delivery of anthralin: preparation, comparative evaluation and clinical assessment in psoriatic patients. Pharmaceutics. 2020;12(5):446-56. doi: 10.3390/pharmaceutics12050446, PMID 32403379.

Chiu MH, Prenner EJ. Differential scanning calorimetry: an invaluable tool for a detailed thermodynamic characterization of macromolecules and their interactions. J Pharm Bioallied Sci. 2011;3(1):39-59. doi: 10.4103/0975-7406.76463, PMID 21430954.

Tavano L. Liposomal gels in enhancing skin delivery of drugs. Percutaneous penetration enhancers chemical methods in penetration enhancement: drug manipulation strategies and vehicle effects. Berlin, Heidelberg: Springer; 2015. p. 329-41.

Mitkari B, Korde S, Mahadik K. Formulation and evaluation of topical liposomal gel for fluconazole. Indian J Pharm Educ Res. 2010;44:324-33.

Meghana G, Karri VVSR, Talluri S, Gunda R. Formulation and evaluation of tolnaftate loaded topical liposomal gel for effective skin drug delivery to treat fungal diseases. J Chem Pharm Res. 2014;6(10):856-66.

Shukla R, Tiwari G, Tiwari R, Rai AK. Formulation and evaluation of the topical ethosomal gel of melatonin to prevent UV radiation. J Cosmet Dermatol. 2020;19(8):2093-104.

Gupta SB, Bhairy SR, Hirlekar RS. Formulation development, characterization and assessment of in vitro antifungal efficacy against candida albicans of diallyl disulphide liposomal gel using 32 factorial design. J Drug Delivery Ther. 2019;9(2):105-17. doi: 10.22270/jddt.v9i2.2522.

Naveentaj S, Muzib YI, Radha R. Design and optimization of fluconazole-loaded pharmacosome gel for enhancing transdermal permeation and treating fungal infections through box-Behnken design. Integr J Appl Pharm. 2023;15(1):131-40.

Thorat YS, Kote NS, Patil VV, Hosmani AH. Formulation and evaluation of liposomal gel containing extract of piprine. Int J Curr Pharm. 2020;12(3):126-9.

Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm. 2010;67(3):217-23. PMID 20524422.

Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123-33. doi: 10.1016/s0928-0987(01)00095-1, PMID 11297896.

Roy D, Das S, Samanta A. Design and in vitro release kinetics of liposomal formulation of acyclovir. Int J Appl Pharm. 2019;11(6):61-5.

Kumar S, Malick AW, Meltzer NM, Mouskountakis JD, Behl CR. Studies of in vitro skin permeation and retention of a leukotriene antagonist from topical vehicles with a hairless guinea pig model. J Pharm Sci. 1992;81(7):631-4. doi: 10.1002/jps.2600810708, PMID 1403694.

Gupta M, Goyal AK, Paliwal SR, Paliwal R, Mishra N, Vaidya B. Development and characterization of effective topical liposomal system for localized treatment of cutaneous candidiasis. J Liposome Res. 2010;20(4):341-50. doi: 10.3109/08982101003596125, PMID 20163329.

Fantini A, Demurtas A, Nicoli S, Padula C, Pescina S, Santi P. In vitro skin retention of crisaborole after topical application. Pharmaceutics. 2020;12(6):491-9. doi: 10.3390/pharmaceutics12060491, PMID 32481663.

Dainichi T, Ueda S, Imayama S, Furue M. Excellent clinical results with a new preparation for chemical peeling in acne: 30% salicylic acid in polyethylene glycol vehicle. Dermatol Surg. 2008;34(7):891-9. doi: 10.1111/j.1524-4725.2008.34174.x, PMID 18363720.

Schubert MA, Müller Goymann CC. Solvent injection as a new approach for manufacturing lipid nanoparticles-evaluation of the method and process parameters. Eur J Pharm Biopharm. 2003;55(1):125-31. doi: 10.1016/s0939-6411(02)00130-3, PMID 12551713.

Moghddam SR, Ahad A, Aqil M, Imam SS, Sultana Y. Formulation and optimization of niosomes for topical diacerein delivery using 3-factor, 3-level Box-Behnken design for the management of psoriasis. Mater Sci Eng C Mater Biol Appl. 2016;69:789-97. doi: 10.1016/j.msec.2016.07.043, PMID 27612773.

Deniz A, Sade A, Severcan F, Keskin D, Tezcaner A, Banerjee S. Celecoxib-loaded liposomes: effect of cholesterol on encapsulation and in vitro release characteristics. Biosci Rep. 2010;30(5):365-73. doi: 10.1042/BSR20090104.

Lee SC, Lee KE, Kim JJ, Lim SH. The effect of cholesterol in the liposome bilayer on the stabilization of incorporated retinol. J Liposome Res. 2005;15(3-4):157-66. doi: 10.1080/08982100500364131, PMID 16393907.

Farzaneh H, Ebrahimi Nik M, Mashreghi M, Saberi Z, Jaafari MR, Teymouri M. A study on the role of cholesterol and phosphatidylcholine in various features of liposomal doxorubicin: from liposomal preparation to therapy. Int J Pharm. 2018;551(1-2):300-8. doi: 10.1016/j.ijpharm.2018.09.047, PMID 30243944.

Fan M, Xu S, Xia S, Zhang X. Preparation of salidroside nano-liposomes by ethanol injection method and in vitro release study. Eur Food Res Technol. 2008;227(1):167-74.

Magarkar A, Dhawan V, Kallinteri P, Viitala T, Elmowafy M, Rog T. Cholesterol level affects surface charge of lipid membranes in saline solution. Sci Rep. 2014;4:5005. doi: 10.1038/srep05005. PMID 24845659.

Sala M, Miladi K, Agusti G, Elaissari A, Fessi H. Preparation of liposomes: A comparative study between the double solvent displacement and the conventional ethanol injection-from laboratory scale to large scale. Colloids Surf A Physicochem Eng Asp. 2017;524:71-8.

Gouda A, Sakr OS, Nasr M, Sammour O. Ethanol injection technique for liposomes formulation: an insight into the development, influencing factors, challenges and applications. J Drug Deliv Sci Technol. 2021;61:102174.

Jedlovszky P, Mezei M. Effect of cholesterol on the properties of phospholipid membranes. J Phys Chem B. 2003;107(22):5311-21. doi: 10.1021/jp0219505.

Mousa IA, Hammady TM, Gad S, Zaitone SA, El-Sherbiny M, Sayed OM. Formulation and characterization of metformin-loaded ethosomes for topical application to experimentally induced skin cancer in mice. Pharmaceuticals (Basel). 2022;15(6):774-85. doi: 10.3390/ph15060657, PMID 35745575.

Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10(2). doi: 10.3390/pharmaceutics10020057, PMID 29783687.

Kitagawa S, Kasamaki M. Enhanced delivery of retinoic acid to skin by cationic liposomes. Chem Pharm Bull (Tokyo). 2006;54(2):242-4. doi: 10.1248/cpb.54.242, PMID 16462074.

Lin H, Xie Q, Huang X, Ban J, Wang B, Wei X. Increased skin permeation efficiency of imperatorin via charged ultra deformable lipid vesicles for transdermal delivery. Int J Nanomedicine. 2018;13:831-42. doi: 10.2147/IJN.S150086, PMID 29467573.

Choi JM, Kim K, Cho E, Jung S. Solubility enhancement of salicylic acid by complexation with succinoglycan monomers isolated from sinorhizobium meliloti. Bull Korean Chem Soc. 2012;33(6):2091-4. doi: 10.5012/bkcs.2012.33.6.2091.

Elbagerma MA, Edwards HGM, Munshi T, Scowen IJ. Identification of a new co-crystal of salicylic acid and benzamide of pharmaceutical relevance. Anal Bioanal Chem. 2010;397(1):137-46. doi: 10.1007/s00216-009-3375-7, PMID 20039022.

Rahman SA, Abdelmalak NS, Badawi A, Elbayoumy T, Sabry N, El Ramly A. Formulation of tretinoin-loaded topical proniosomes for treatment of acne: in vitro characterization, skin irritation test and comparative clinical study. Drug Deliv. 2015;22(6):731-9. doi: 10.3109/10717544.2014.896428. PMID 24670094.

Jain A, Jain SK. In vitro release kinetics model fitting of liposomes: an insight. Chem Phys Lipids. 2016;201(16):28-40. doi: 10.1016/j.chemphyslip.2016.10.005, PMID 27983957.

Paul S, Jana M, Bose A, Bhattacharjee S. Topical liposomal gel: A new strategy of novel drug delivery. World J Pharm Sci. 2020;6:568-77.

Yokomizo Y, Sagitani H. Effects of phospholipids on the percutaneous penetration of indomethacin through the dorsal skin of guinea pigs in vitro. J Control Release. 1996;38(2):267-74.

Cooper ER. Increased skin permeability for lipophilic molecules. J Pharm Sci. 1984;73(8):1153-6. doi: 10.1002/jps.2600730831, PMID 6491922.