THE CHOICE OF COMPONENTS AND THE IMPACT OF SURFACTANTS AND CO-SURFACTANTS ON EPLERENONE NANOEMULSION SYNTHESIS FOR GEL-BASED TRANSDERMAL APPLICATION

MAHESH T GAIKWAD; RAJENDRA P MARATHE; INAYAT B PATHAN

doi:10.22159/ijap.2024v16i6.52044

Authors

MAHESH T GAIKWAD Govt College of Pharmacy, Opp. Govt. Polytechnic, Osmanpura, Chhatrapati Sambhajinagar-431005, Maharashtra, India https://orcid.org/0000-0003-3252-7969
RAJENDRA P MARATHE Department of Pharmaceutical Chemistry, Govt College of Pharmacy, Opp. Govt. Polytechnic, Osmanpura, Chhatrapati Sambhajinagar-431005, Maharashtra, India
INAYAT B PATHAN Department of Pharmaceutics, Govt College of Pharmacy, Opp. Govt. Polytechnic, Osmanpura, Chhatrapati Sambhajinagar-431005, Maharashtra, India

DOI:

https://doi.org/10.22159/ijap.2024v16i6.52044

Keywords:

Smix, Oil phase, Nanoemulsion region, Pseudo Ternary Phase Diagram, Emulsification efficacy

Abstract

Objective: This research aims to establish an efficient methodology for selecting nanoemulsion components to synthesize eplerenone nanoemulsion for gel-based transdermal applications.

Methods: The chemical compatibility study of eplerenone was investigated by FTIR, DSC, and solubility in oils, surfactants, and co-surfactants as the criteria for choice. We used visual appraisal and grading to assess the effectiveness of emulsification. Various excipients were tested depending on solubility. The final appearance, dispersibility, and ease of emulsification were used to visually assess the degree of self-emulsification of oil and emulsifier in a 1:3 mass ratio. Co-surfactants were assessed by mixing particular emulsifiers in a 2:1 (w/w) ratio with co-surfactants, and the oily component was added at a 1:3 (w/w) ratio to evaluate Smix's emulsification potential. A central composite design synthesized, evaluated, and optimized eplerenone nanoemulsions. Optimized nanoemulsions were characterized after a thermodynamic stability study for droplet size, ζ potential, viscosity, refractive index, pH measurements, and TEM. All the selected formulations were found to be stable, and the droplet size was found to be<110 nm.

Results: Eplerenone was chemically compatible, and its maximum solubility was 171.3±0.92 and 169.3±2.22 in Kollicream^®OA and Paceol, respectively. The evidence impressively found that Tween 20 and Kolliphor^®EL were discovered as active emulsifiers, and Transcutol^®P was revealed to be a co-surfactant. Outcomes showed that the emulsification efficacy of Kolliphor^®EL (3% w/w) was able to emulsify Kollicream^®OA (1% w/w), and Paceol failed. As well, Smix [Kolliphor^®EL (2% w/w) and Transcutol^®P (1% w/w)] were able to emulsify Kollicream^®OA (1% w/w).

Conclusion: The main conclusion from this work is the application of a visual appraisal and grading system to assess the final appearance, dispersibility, and ease of emulsification to eradicate the toxicity and irritation that nanoemulsions can cause. Optimised nanoemulsions can further formulate eplerenone's nanoemulsion gel for transdermal application.

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References

Chung EJ, Leon L, Rinaldi C, Editors. 21-nanoemulsions. In: Nanoparticles for biomedical applications. Elsevier; 2020. p. 371-84. Available from: https://www.sciencedirect.com/science/article/pii/B9780128166628000217.

Solans C, Izquierdo P, Nolla J, Azemar N, Garcia Celma MJ. Nano emulsions. Curr Opin Colloid Interface Sci. 2005;10(3-4):102-10. doi: 10.1016/j.cocis.2005.06.004.

Sharma N, Bansal M, Visht S, Sharma PK, Kulkarni GT. Nanoemulsion: a new concept of delivery system. Chron Young Sci. 2010;1(2):2-6.

Nor Bainun I, Alias NH, Syed Hassan SS. Nanoemulsion: formation characterization properties and applications a review. AMR. 2015 Jul;1113:147-52. doi: 10.4028/www.scientific.net/AMR.1113.147.

Gupta A, Badruddoza AZ, Doyle PS. A general route for nanoemulsion synthesis using low energy methods at constant temperature. Langmuir. 2017 Jul 18;33(28):7118-23. doi: 10.1021/acs.langmuir.7b01104, PMID 28654749.

Gheorghe I, Saviuc C, Ciubuca B, Lazar V, Chifiriuc MC. Nanodrug delivery systems for transdermal drug delivery. In: William Andrew Publishing; 2019. Chapter 8. Nanomaterials for drug delivery and therapy. Grumezescu AM, editor. 2019. p. 225-44. Available from: https://www.sciencedirect.com/science/article/pii/B9780128165058000102. [Last accessed on 07 Oct 2024]

McClements DJ, Jafari SM. General aspects of nanoemulsions and their formulation. Nanoemulsions. 2018:3-20. doi: 10.1016/B978-0-12-811838-2.00001-1.

Shah MR, Imran M, Ullah S. Chapter 4. Nanoemulsions. In: Lipid based nanocarriers for drug delivery and diagnosis; 2017. p. 111-37.

Tirnaksiz F, Akkus S, Celebi N. 9-nanoemulsions as drug delivery systems. In: Monzer F. editor. Colloids in drug delivery. CRC Press, Taylor & Francis Group; 2010. p. 221-44. doi: 10.1201/9781439818268-c9.

Thakur A, Walia K, Kumar SL. Nanoemulsion in enhancement of bioavailability of poorly soluble drugs: a review. Pharmacophore. 2013;4(1):15-25.

Shinde R, Velraj M. Formulation optimization and characterization of transdermal drug delivery systems containing eplerenone. Int J App Pharm. 2022 Jan 1;14(1):198-207. doi: 10.22159/ijap.2022v14i1.42827.

Eplerenone: Uses. Interactions, mechanism of action. Drugbank Online. Available from: https://go.drugbank.com/drugs/DB00700. [Last accessed on 30 Jun 2017].

Aparna C, Srinivas P, Rao Patnaik KS. Enhanced transdermal permeability of telmisartan by a novel nanoemulsion gel. Int J Pharm Pharm Sci. 2015;7(4):335-42.

Chrismaurin F, Dwiastuti R, Chabib L, Yuliani SH. The effect of olive oil tween 60 and span 20 on physical characteristics of quercetin nanoemulgel. Int J App Pharm. 2023 Jan 1;15(1):212-7. doi: 10.22159/ijap.2023v15i1.46423.

Azeem A, Rizwan M, Ahmad FJ, Khar RK, Iqbal Z, Talegaonkar S. Components screening and influence of surfactant and cosurfactant on nanoemulsion formation. Curr Nanosci. 2009;5(2):220-6. doi: 10.2174/157341309788185505.

Jalajakshi MN, Chandrakala V, Srinivasan S. An overview: recent development in transdermal drug delivery. Int J Pharm Pharm Sci. 2022 Oct 1;14(10):1-9.

Shailaja B, Swarna K, Afreen M, Kumar AA. A rapid assay method development and validation for the estimation of eplerenone in tablets by UV spectrophotometry. Int J Pharm Pharm Sci. 2015 Jul 22;7(9):327-30.

Banode VS, Khedekar PB, Tarte PS. Spectrophotometric estimation of eplerenone in bulk drug and tablets. Int J ChemTech Res. 2011;3(1):398-402.

Patravale V, Borhade V, Pathak S, Sharma S. Clotrimazole nanoemulsion for malaria chemotherapy part I: preformulation studies formulation design and physicochemical evaluation. Int J Pharm. 2012 Jul 15;431(1-2):138-48.

Chadha R, Bhandari S. Drug excipient compatibility screening role of thermoanalytical and spectroscopic techniques. J Pharm Biomed Anal. 2014 Jan 18;87:82-97. doi: 10.1016/j.jpba.2013.06.016, PMID 23845418.

Secilmis Canbay H, Polat M, Doganturk M. Study of stability and drug excipient compatibility of estriol. Bilge Int J Sci Technol Res. 2019 Sep 30;3(2):102-7. doi: 10.30516/bilgesci.582054.

Bali V, Ali M, Ali J. Study of surfactant combinations and development of a novel nanoemulsion for minimising variations in bioavailability of ezetimibe. Colloids and Surfaces B: Biointerfaces. 2010 Apr 1;76(2):410-20. doi: 10.1016/j.colsurfb.2009.11.021.

Eplerenone Official Monograph. The Japanese Pharmacopoeia. 17th ed. The Minister of Health, Labour and Welfare; 2016. p. 874-5.

Lakavath SK, Ahad HA. Construction of ternary phase diagram for three-component system (oil-water-surfactant) as a preliminary step before formulating a nanoemulsion. Eur Chem Bull. 2023;12(10):10669-79.

Kumar B, Singh BP, Jain SK, Shafaat K. Development and characterization of a nanoemulsion gel formulation for transdermal delivery of carvedilol. Int J Drug Dev Res. 2012;4(1):151-61.

Kaur K, Kumar R, Mehta SK. Formulation of saponin stabilized nanoemulsion by ultrasonic method and its role to protect the degradation of quercitin from UV light. Ultrason Sonochem. 2016 Jul 1;31:29-38. doi: 10.1016/j.ultsonch.2015.11.017, PMID 26964921.

Mohamadi Saani S, Abdolalizadeh J, Zeinali Heris S. Ultrasonic/sonochemical synthesis and evaluation of nanostructured oil in water emulsions for topical delivery of protein drugs. Ultrason Sonochem. 2019 Jul 1;55:86-95. doi: 10.1016/j.ultsonch.2019.03.018, PMID 31084795.

Modarres Gheisari SM, Gavagsaz Ghoachani R, Malaki M, Safarpour P, Zandi M. Ultrasonic nano-emulsification a review. Ultrason Sonochem. 2019 Apr;52:88-105. doi: 10.1016/j.ultsonch.2018.11.005, PMID 30482437.

Subramaniyan G, Mohanan J, Kuttalingam A, Narayanasamy D. Implementing central composite design for the development of tacrolimus film for sublingual administration. Int J Appl Pharm. 2023;15(3):35-42.

Azeem A, Rizwan M, Ahmad FJ, Iqbal Z, Khar RK, Aqil M. Nanoemulsion components screening and selection: a technical note. AAPS Pharm Sci Tech. 2009;10(1):69-76. doi: 10.1208/s12249-008-9178-x.

Elmataeeshy ME, Sokar MS, Bahey-El-Din M, Shaker DS. Enhanced transdermal permeability of terbinafine through novel nanoemulgel formulation; development in vitro and in vivo characterization. Future Journal of Pharmaceutical Sciences. 2018 Jun;4(1):18-28. doi: 10.1016/j.fjps.2017.07.003.

Shinde PB. Component screening of miconazole nitrate nanoemulsion. Asian J Biomed Pharm Sci. 2013;3(19):33-40.

Khan AW, Kotta S, Ansari SH, Sharma RK, Ali J. Self nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid naringenin: design characterization in vitro and in vivo evaluation. Drug Deliv. 2015 Jun 1;22(4):552-61. doi: 10.3109/10717544.2013.878003.

Shakeel F. Criterion for excipients screening in the development of nanoemulsion formulation of three anti-inflammatory drugs. Pharm Dev Technol. 2010;15(2):131-8. doi: 10.3109/10837450903055502, PMID 19911951.

Elizabeth Jacob N, Selvam PR, Chandy V. Modified oils used of self nanoemulsifying drug delivery system. World J Pharm Res. 2015;11(5):728-41.

Rai VK, Mishra N, Yadav KS, Yadav NP. Nanoemulsion as pharmaceutical carrier for dermal and transdermal drug delivery: formulation development stability issues basic considerations and applications. J Control Release. 2018 Jan 28;270:203-25. doi: 10.1016/j.jconrel.2017.11.049, PMID 29199062.

Cortes H, Hernandez Parra H, Bernal Chavez SA, Del Prado Audelo ML, Caballero Floran IH, Borbolla Jimenez FV. Non ionic surfactants for stabilization of polymeric nanoparticles for biomedical uses. Materials (Basel). 2021 Jun 2;14(12):1-39. doi: 10.3390/ma14123197, PMID 34200640.

Pant A, Jha K, Singh M. Role of excipients HLB value in microemulsion system. IOSR J Pharm Biol Sci. 2019;14(2):1-6. doi: 10.9790/3008-1402020106.

Choudhury H, Zakaria NF, Tilang PA, Tzeyung AS, Pandey M, Chatterjee B. Formulation development and evaluation of rotigotine mucoadhesive nanoemulsion for intranasal delivery. J Drug Deliv Sci Technol. 2019 Dec 1;54:101301. doi: 10.1016/j.jddst.2019.101301.

Hosseinpour S, Gotz V, Peukert W. Effect of surfactants on the molecular structure of the buried oil/water interface. Angew Chem Int Ed Engl. 2021 Nov 15;60(47):25143-50. doi: 10.1002/anie.202110091, PMID 34478223.

Schreiner TB, Santamaria Echart A, Ribeiro A, Peres AM, Dias MM, Pinho SP. Formulation and optimization of nanoemulsions using the natural surfactant saponin from quillaja bark. Molecules. 2020 Mar 27;25(7):1538. doi: 10.3390/molecules25071538, PMID 32230976.

Jadhav C, Kate V, Payghan SA. Investigation of effect of a non-ionic surfactant on preparation of griseofulvin non-aqueous nanoemulsion. J Nanostruct Chem. 2015 Mar 1;5(1):107-13. doi: 10.1007/s40097-014-0141-y.

Smail SS, Ghareeb MM, Omer HK, Al Kinani AA, Alany RG. Studies on surfactants cosurfactants and oils for prospective use in formulation of ketorolac tromethamine ophthalmic nanoemulsions. Pharmaceutics. 2021 Apr 1;13(4):1-13. doi: 10.3390/pharmaceutics13040467, PMID 33808316.

Jadhav CM. Investigating application of non-aqueous microemulsion for drug delivery: a review. AJBPS. 2014;4(29):1-9. doi: 10.15272/ajbps.v4i29.460.

Qadir A, Faiyazuddin MD, Talib Hussain MD, Alshammari TM, Shakeel F. Critical steps and energetics involved in a successful development of a stable nanoemulsion. J Mol Liq. 2016 Feb 1;214:7-18. doi: 10.1016/j.molliq.2015.11.050.

Sneh P, Koland M, NSK. Nanoemulsion components screening of quetiapine fumarate: effect of surfactant and co-surfactant. Asian J Pharm Clin Res. 2015;8(6):136-40.