Formulation Development, Optimization, And Characterization Of Niosomal Nanocarriers For Improved Drug Delivery

Authors

  • Akshay B. Ghanmode
  • Akash S. Malthankar
  • Gajanan M. Jawalkar
  • Dnyanesha N. Somnathe
  • Amruta S. Phuse

Keywords:

Ticagrelor; Niosomes; Preformulation Studies; Factorial Design; Entrapment Efficiency; In-vitro Drug Release; Ex-vivo Permeability; Drug–Excipient Compatibility

Abstract

The present investigation was undertaken to perform comprehensive preformulation studies and develop an optimized niosomal drug delivery system for Ticagrelor with the objective of enhancing its delivery performance. Ticagrelor, a white crystalline powder with a melting point of 138 ± 2 °C, exhibited high solubility in organic solvents such as ethanol and methanol, whereas limited solubility was observed in distilled water and phosphate buffer (pH 6.8). Ultraviolet spectroscopic analysis confirmed the identity of the drug, showing maximum absorbance (λ_max) at 255 nm in ethanol and 256.2 nm in phosphate buffer. Fourier transform infrared (FTIR) spectroscopy revealed no significant shifts in characteristic peaks, indicating good compatibility between Ticagrelor and the selected excipients.

Niosomal vesicles were formulated using the ether injection technique and systematically optimized employing a 3² full factorial experimental design. Among the developed formulations, the optimized batch (A9) demonstrated superior performance, achieving an entrapment efficiency of 89.7%, a mean particle size of 280.5 nm, and a zeta potential of −26.8 mV, indicative of satisfactory vesicular stability. Scanning electron microscopy (SEM) confirmed the formation of well-defined, spherical vesicles. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses revealed a reduction in crystallinity of Ticagrelor, suggesting its transformation from a crystalline to an amorphous state upon encapsulation within the niosomes. In-vitro drug release studies demonstrated a sustained release behavior, with cumulative drug release ranging from 20.09% to 91.13%, confirming the controlled release potential of the niosomal system. Ex-vivo permeability studies conducted using a Franz diffusion cell apparatus showed significantly enhanced drug permeation from niosomal formulations compared to the pure drug, indicating improved transmembrane transport. Precompression parameters confirmed acceptable flow properties of the powder blend. Furthermore, evaluation of the compressed niosomal tablets revealed satisfactory mechanical strength, with hardness of 5.2 kg/cm², friability of 0.652%, and drug content uniformity of 90.7%, all of which complied with pharmacopeial specifications. Overall, the optimized Ticagrelor-loaded niosomal formulation demonstrated enhanced stability, controlled drug release, and improved permeability, highlighting its potential as an effective and promising delivery system for improving the bioavailability of Ticagrelor....

Downloads

Download data is not yet available.

References

[1] Jain S, Jain V, Mahajan SC. Lipid-based vesicular drug delivery systems. Adv Pharm. 2014; 2014:1-12.

[2] Ge X, Wei M, He S, Yuan WE. Advances of non-ionic surfactant vesicles (niosomes) and their application in drug delivery. Pharmaceutics. 2019 Jan 29;11(2):55.

[3] Liga S, Paul C, Moacă EA, Péter F. Niosomes: composition, formulation techniques, and recent progress as delivery systems in cancer therapy. Pharmaceutics. 2024 Feb 4;16(2):223.

[4] Kaur D, Kumar S. Niosomes: present scenario and future aspects. J Drug Deliv Ther. 2018;8(5):35-43.

[5] Rajera R, Nagpal K, Singh SK, Mishra DN. Niosomes: a controlled and novel drug delivery system. Biol Pharm Bull. 2011;34(7):945-53.

[6] Manosroi A, Khanrin P, Lohcharoenkal W, Werner RG, Götz F, Manosroi W, et al. Transdermal absorption enhancement through rat skin of gallidermin loaded in niosomes. Int J Pharm. 2010;392(1-2):304-10.

[7] Kumar GP, Rajeshwarrao P. Nonionic surfactant vesicular systems for effective drug delivery—an overview. Acta Pharm Sin B. 2011;1(4):208-19.

[8] Kazi KM, Mandal AS, Biswas N, Guha A, Chatterjee S, Behera M, et al. Niosome: a future of targeted drug delivery systems. J Adv Pharm Technol Res. 2010;1(4):374-80.

[9] Ag Seleci D, Seleci M, Walter JG, Stahl F, Scheper T. Niosomes as nanoparticular drug carriers: fundamentals and recent applications. J Nanomater. 2016;2016:7372306.

[10] Biju SS, Telegaonar S, Mishra PR, Khar RK. Vesicular system: an overview. Indian J Pharm Sci. 2006;68(2):141-53.

[11] Vyas SP, Khar RK. Controlled drug delivery system: concept and advances. New Delhi: CBS Publishers and Distributors; 2002.

[12] Witika BA, Bassey KE, Demana PH, Siwe-Noundou X, Poka MS. Current advances in specialised niosomal drug delivery: manufacture, characterization and drug delivery applications. Int J Mol Sci. 2022 Aug 26;23(17):9668.

[13] Moammeri A, Chegeni MM, Sahrayi H, Ghafelehbashi R, Memarzadeh F, Mansouri A, et al. Current advances in niosomes applications for drug delivery and cancer treatment. Mater Today Bio. 2023 Oct 21;100837.

[14] Rosengren A, Wallentin L, Simoons M, et al. Age, clinical presentation, and outcome of acute coronary syndromes in the Euroheart acute coronary syndrome survey. Eur Heart J. 2006;27(7):789-95. doi:10.1093/eurheartj/ehi774.

[15] Cattaneo M, Schulz R, Nylander S. Adenosine-mediated effects of ticagrelor: evidence and potential clinical relevance. J Am Coll Cardiol. 2014;63(23):2503–9.

[16] Dracup K, McKinley S, Doering LV, et al. Acute coronary syndrome: what do patients know? Arch Intern Med. 2008;168(10):1049-54. doi:10.1001/archinte.168.10.1049.

[17] Sanchis-Gomar F, Perez-Quilis C, Leischik R, Lucia A. Epidemiology of coronary heart disease and acute coronary syndrome. Ann Transl Med. 2016;4(13):1-12. doi:10.21037/atm.2016.06.33.

[18] Santos-Gallego CG, Picatoste B, Badimón JJ. Pathophysiology of acute coronary syndrome. Curr Atheroscler Rep. 2014;16:1-9. doi:10.1007/s11883-014-0401-9.

[19] Fuster V, Fayad ZA, Badimon JJ. Acute coronary syndromes: biology. Lancet. 1999;353:s5-s9. doi:10.1016/S0140-6736(99)90234-9.

[20] Gach O, El HZ, Lancellotti P. Acute coronary syndrome. Rev Med Liege. 2018;73(5-6):243-50.

[21] CTX Lifesciences. Material Safety Data Sheet. p. 1-5.

[22] DrugBank. DBSALT002974 [Internet]. Available from: https://go.drugbank.com/salts/DBSALT002974.

[23] Raymond R, Sheskey P, Owen S. Sorbitan Monostearate. In: Galichet L, McIndoe L, Owen S, Weller P, editors. Handbook of Pharmaceutical Excipients. 5th ed. London: Pharmaceutical Press; 2006. p. 713-717.

[24] Raymond R, Sheskey P, Owen S. Cholesterol. In: Galichet L, McIndoe L, Owen S, Weller P, editors. Handbook of Pharmaceutical Excipients. 5th ed. London: Pharmaceutical Press; 2006. p. 182-184.

[25] Raymond R, Sheskey P, Owen S. Magnesium Stearate. In: Galichet L, McIndoe L, Owen S, Weller P, editors. Handbook of Pharmaceutical Excipients. 5th ed. London: Pharmaceutical Press; 2006. p. 430-433.

[26] Raymond R, Sheskey P, Owen S. Talc. In: Galichet L, McIndoe L, Owen S, Weller P, editors. Handbook of Pharmaceutical Excipients. 5th ed. London: Pharmaceutical Press; 2006. p. 767-769.

[27] Raymond R, Sheskey P, Owen S. Microcrystalline Cellulose. In: Galichet L, McIndoe L, Owen S, Weller P, editors. Handbook of Pharmaceutical Excipients. 5th ed. London: Pharmaceutical Press; 2006. p. 132-136.

[28] Shewaiter MA, Selim AA, Rashed HM, Moustafa YM, Gad S. Niosomal formulation of mefenamic acid for enhanced cancer targeting: preparation, characterization, and biodistribution study using radiolabeling technique. J Cancer Res Clin Oncol. 2023 Dec; 149(20):18065-80.

[29] Bansal S, Aggarwal G, Chandel P, Harikumar SL. Design and development of cefdinir niosomes for oral delivery. J Pharm Bioallied Sci. 2013 Oct 1; 5(4):318-25.

[30] Ertekin ZC, Bayindir ZS, Yuksel N. Stability studies on piroxicam encapsulated niosomes. Curr Drug Deliv. 2015 Apr 1; 12(2):192-9.

[31] Khan DH, Bashir S, Khan MI, Figueiredo P, Santos HA, Peltonen L. Formulation optimization and in vitro characterization of rifampicin and ceftriaxone dual drug-loaded niosomes with high-energy probe sonication technique. J Drug Deliv Sci Technol. 2020 Aug 1; 58:101763.

[32] Hasan AA, Madkor H, Wageh S. Formulation and evaluation of metformin hydrochloride-loaded niosomes as a controlled release drug delivery system. Drug Deliv. 2013 Apr 1; 20(3-4):120-6.

[33] Rasve VR, Chakraborty AK, Jain SK, Vengurlekar S., Comparative evaluation of antidiabetic activity of ethanolic leaves extract of Clematis triloba and their SMEDDS formulation in streptozotocin-induced diabetic rats. J Popul Ther Clin Pharmacol. 2022; 29(4):959-71. doi:10.53555/jptcp.v29i04.2360.

[34] Naderi R, Pardakhty A, Abbasi MF, Ranjbar M, Iranpour M. Preparation and evaluation of crocin-loaded nanoniosomes and their effects on ischemia–reperfusion injuries in rat kidney. Sci Rep. 2021 Dec 7;11(1):23525.

[35] Ghafelehbashi R, Akbarzadeh I, Yaraki MT, Lajevardi A, Fatemizadeh M, Saremi LH. Preparation, physicochemical properties, in vitro evaluation, and release behavior of cephalexin-loaded niosomes. Int J Pharm. 2019 Oct 5; 569:118580.

[36] Khan DH, Bashir S, Figueiredo P, Santos HA, Khan MI, Peltonen L. Process optimization of ecological probe sonication technique for the production of rifampicin-loaded niosomes. J Drug Deliv Sci Technol. 2019 Apr 1; 50:27-33.

[37] Narade S, Pore Y. Optimization of ex vivo permeability characteristics of berberine in the presence of quercetin using 3² full factorial designs. J Appl Pharm Sci. 2019 Feb 4; 9(1):073-82.

[38] Sánchez AB, Calpena AC, Mallandrich M, Clares B. Validation of an ex vivo permeation method for the intestinal permeability of different BCS drugs and its correlation with Caco-2 in vitro experiments. Pharmaceutics. 2019 Nov 29; 11(12):638.

[39] Indian Pharmacopeia. Government of Ministry of Health and Family Welfare. Published by the Controller of Publication, Delhi. Vol. II. 2007. p. 1815-20.

[40] Fouad SA, Teaima MH, Gebril MI, Abd Allah FI, El-Nabarawi MA, Elhabal SF. Formulation of novel niosomal repaglinide chewable tablets using coprocessed excipients: in vitro characterization, optimization, and enhanced hypoglycemic activity in rats. Drug Deliv. 2023 Dec 31;30(1):2181747.

[41] Rasve V, Chakraborty AK, Jain SK, Vengurlekar S. Study of phytochemical profiling and in vitro studies on antioxidant properties of ethanolic extract of Clematis triloba. Eur Chem Bull. 2022;11(12):2658–2677. doi:10.53555/ecb/2022.11.12.2162022.

[42] Patel SS, Patel MR, Patel MJ. Formulation and evaluation of microsponge-based nicorandil sustained release tablet. J Sci Res. 2017;9(3):285-96.

[43] Hazarika JN, Deb P. Formulation, evaluation, and optimization of immediate release tablet of aceclofenac by direct compression method. Int J Curr Pharm Res. 2017;9(3):118-22.

[44] Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics - A Treatise. 2nd ed. New Delhi: Jaypee Publishers; 2002. p. 400-43.

[45] Arvapally S, Harini M, Harshitha G, Arunkumar A. Formulation and in vitro evaluation of glipizide nanosponges. Am J Pharm Tech Res. 2017;7(3):342-60.

Vyas A, Saraf S, Saraf S. Cyclodextrin-based novel drug delivery systems. J Incl Phenom Macrocycl Chem. 2008 Oct;62:23-42.

Downloads

Published

2025-12-12

How to Cite

1.
B. Ghanmode A, S. Malthankar A, M. Jawalkar G, N. Somnathe D, S. Phuse A. Formulation Development, Optimization, And Characterization Of Niosomal Nanocarriers For Improved Drug Delivery. J Neonatal Surg [Internet]. 2025 Dec. 12 [cited 2026 Sep. 5];14(32S):10994-1010. Available from: https://jneonatalsurg.com/index.php/jns/article/view/10357

Issue

Vol. 14 No. 32S (2025): Journal of Neonatal Surgery

Section

Original Article

License

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

You are free to:

  • Adapt — remix, transform, and build upon the material for any purpose, even commercially.

Terms:

  • Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
  • No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.