NANOEMULSION-BASED DELIVERY OF TERMINALIA ARJUNA BARK EXTRACT: SNEDDS FORMULATION, OPTIMIZATION, AND IN VIVO EVALUATION

PANKAJ; MANISH VYAS; SANJEEV KUMAR SAHU; PALWINDER KAUR

doi:10.22159/ijap.2025v17i6.55374

Authors

PANKAJ Pharmaceutical Sciences, Lovely Professional University, Phagwara-144411, Punjab, India. Development Cell, Parul University, Vadodara-391760, Gujarat India https://orcid.org/0009-0004-8803-6872
MANISH VYAS Pharmaceutical Sciences, Lovely Professional University, Phagwara-144411, Punjab, India https://orcid.org/0000-0002-1426-2277
SANJEEV KUMAR SAHU School of Pharmaceutical Sciences, Lovely Professional University, Phagwara-144411, Punjab, India
PALWINDER KAUR Pharmaceutical Sciences, Lovely Professional University, Phagwara-144411, Punjab, India

DOI:

https://doi.org/10.22159/ijap.2025v17i6.55374

Keywords:

Arjuna, SNEDDS, Nanoemulsion, Stability, Antihypertensive activity

Abstract

Objective: Terminalia arjuna (T. arjuna), the stem bark of which has long been valued for its strong cardioprotective and antioxidant effects, primarily due to its diverse range of bioactive compounds. Despite its potential, its clinical use has been limited due to its poor water solubility and low oral bioavailability.

Methods: In this study, an optimized Self-Nanoemulsifying Drug Delivery System (SNEDDS) of T. arjuna extract was developed to overcome these limitations and improve the oral delivery of the extract. Later, the formulation was subjected to stability analysis and preclinical analysis to check the effectiveness of the developed dosage form.

Results: In this research, the SNEDDS formulation was optimized using a reference ratio of the oil (Labrafil), surfactant (Tween 80), and co-surfactant (Transcutol P). The resulting formulation displayed a globule size of 325.66 nm, a polydispersity index (PDI) of 0.252, and a zeta potential of-29.7 mV. The results of the in vivo study showed significant improvements for all groups compared to the control. The standard drug and high-dose SNEDDS groups had the most pronounced effects, while the crude extract and low-dose SNEDDS (500 mg/kg) showed milder responses. The SNEDDS formulation of T. arjuna enhanced both efficacy and safety, highlighting its potential for improving the bioavailability of natural extracts.

Conclusion: Overall, the SNEDDS approach is a promising method for enhancing the therapeutic effectiveness of T. arjuna, particularly in managing cardiovascular conditions.

References

1. Singh P, Sharma D, Singh A, Singh A. A comprehensive review for drug target on Terminalia arjuna (roxb.): ethnopharmacological, phytochemical, pharmacognostical and clinical significance. Asian J Res Chem. 2023 Nov 28;16(6):448-52. doi: 10.52711/0974-4150.2023.00074.

2. Ameta RK, Soni K, Bhattarai A. Recent advances in improving the bioavailability of hydrophobic/lipophilic drugs and their delivery via self-emulsifying formulations. Colloids Interfaces. 2023 Feb 17;7(1):16. doi: 10.3390/colloids7010016.

3. Jain AK, Jain S, Abourehab MA, Mehta P, Kesharwani P. An insight on topically applied formulations for management of various skin disorders. J Biomater Sci Polym Ed. 2022 Dec 12;33(18):2406-32. doi: 10.1080/09205063.2022.2103625, PMID 35848901.

4. Kesharwani P, Sheikh A, Abourehab MA, Salve R, Gajbhiye V. A combinatorial delivery of survivin targeted siRNA using cancer-selective nanoparticles for triple negative breast cancer therapy. J Drug Deliv Sci Technol. 2023 Feb;80:104164. doi: 10.1016/j.jddst.2023.104164.

5. Date AA, Desai N, Dixit R, Nagarsenker M. Self-nanoemulsifying drug delivery systems: formulation insights, applications and advances. Nanomedicine (Lond). 2010 Dec 14;5(10):1595-616. doi: 10.2217/nnm.10.126, PMID 21143036.

6. Liu Z, Parveen N, Rehman U, Aziz A, Sheikh A, Abourehab MA. Unravelling the enigma of siRNA and aptamer-mediated therapies against pancreatic cancer. Mol Cancer. 2023 Jan 12;22(1):8. doi: 10.1186/s12943-022-01696-5, PMID 36635659.

7. Stegemann S, Leveiller F, Franchi D, De Jong H, Linden H. When poor solubility becomes an issue: from early stage to proof of concept. Eur J Pharm Sci. 2007 Aug;31(5):249-61. doi: 10.1016/j.ejps.2007.05.110, PMID 17616376.

8. Merisko Liversidge EM, Liversidge GG. Drug nanoparticles: formulating poorly water-soluble compounds. Toxicol Pathol. 2008 Jan 1;36(1):43-8. doi: 10.1177/0192623307310946, PMID 18337220.

9. Ateeq MA, Aalhate M, Mahajan S, Kumar GS, Sen S, Singh H. Self nanoemulsifying drug delivery system (SNEDDS) of docetaxel and carvacrol synergizes the anticancer activity and enables safer toxicity profile: optimization and in vitro ex vivo and in vivo pharmacokinetic evaluation. Drug Deliv Transl Res. 2023 Oct 17;13(10):2614-38. doi: 10.1007/s13346-023-01342-7, PMID 37067745.

10. Mandal S, Patra A, Samanta A, Roy S, Mandal A, Mahapatra TD. Analysis of phytochemical profile of Terminalia Arjuna bark extract with antioxidative and antimicrobial properties. Asian Pac J Trop Biomed. 2013 Dec;3(12):960-6. doi: 10.1016/S2221-1691(13)60186-0, PMID 24093787.

11. Kazi M, Al Swairi M, Ahmad A, Raish M, Alanazi FK, Badran MM. Evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for poorly water-soluble talinolol: preparation in vitro and in vivo assessment. Front Pharmacol. 2019 May 2;10:459. doi: 10.3389/fphar.2019.00459, PMID 31118895.

12. Larsen AT, Ohlsson AG, Polentarutti B, Barker RA, Phillips AR, Abu Rmaileh R. Oral bioavailability of cinnarizine in dogs: relation to SNEDDS droplet size, drug solubility and in vitro precipitation. Eur J Pharm Sci. 2013 Jan;48(1-2):339-50. doi: 10.1016/j.ejps.2012.11.004, PMID 23178440.

13. Kavitha K, Kanagathara N. Optimization and solubilization study of novel nanoemulsion formulation for 5-fluorouracil by applying pseudoternary phase diagram. Asian J Pharm Clin Res. 2014;7(2):137-9.

14. Katoch P, Singh R, Kaur P, Vyas M, Gulati M, Singh S. Development and characterization of self-nanoemulsifying drug delivery system loaded with fixed oil of Semecarpus anacardium linn. Asian J Pharm. 2016 Jun 28;10(2):144-53. doi: 10.22377/ajp.v10i2.614.

15. Ishak W WM, Zulfakar MH. Optimization development and safety evaluation of olive oil nanoemulsion for topical application: a response surface methodology. Asian J Pharm Clin Res. 2022 Sep 7;15(9):167–73. doi: 10.22159/ajpcr.2022.v15i9.45964.

16. Gupta S, Kesarla R, Omri A. Formulation strategies to improve the bioavailability of poorly absorbed drugs with special emphasis on self-emulsifying systems. ISRN Pharm. 2013 Dec 26;2013:848043. doi: 10.1155/2013/848043, PMID 24459591.

17. Inugala S, Eedara BB, Sunkavalli S, Dhurke R, Kandadi P, Jukanti R. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of Darunavir for improved dissolution and oral bioavailability: in vitro and in vivo evaluation. Eur J Pharm Sci. 2015 Jul;74:1-10. doi: 10.1016/j.ejps.2015.03.024, PMID 25845633.

18. Laxmi M, Bhardwaj A, Mehta S, Mehta A. Development and characterization of nanoemulsion as carrier for the enhancement of bioavailability of artemether. Artif Cells Nanomed Biotechnol. 2015;43(5):334-44. doi: 10.3109/21691401.2014.887018, PMID 24641773.

19. Farooqui H, Upadhyay S, Upadhyay P. Transdermal patches approach towards self-nano-emulsifying drug delivery system (SNEDDS) using essential oil as penetration enhancer. Micro Nanosystems. 2022 Dec;14(4):314-40. doi: 10.2174/1876402914666220221105304.

20. Soto Pina AE, Franklin C, Rani CS, Gottlieb H, Hinojosa Laborde C, Strong R. A novel model of dexamethasone-induced hypertension: use in investigating the role of tyrosine hydroxylase. J Pharmacol Exp Ther. 2016 Sep;358(3):528-36. doi: 10.1124/jpet.116.234005, PMID 27405316.

21. Ramesh P, Palaniappan A. Terminalia arjuna a cardioprotective herbal medicine relevancy in the modern era of pharmaceuticals and green nanomedicine a review. Pharmaceuticals (Basel). 2023 Jan;16(1):126. doi: 10.3390/ph16010126, PMID 36678623.

22. Baloch J, Sohail MF, Sarwar HS, Kiani MH, Khan GM, Jahan S. Self-nanoemulsifying drug delivery system (SNEDDS) for improved oral bioavailability of chlorpromazine: in vitro and in vivo evaluation. Medicina (Kaunas). 2019 May;55(5):210. doi: 10.3390/medicina55050210, PMID 31137751.

23. Buya AB, Beloqui A, Memvanga PB, Preat V. Self-nano-emulsifying drug-delivery systems: from the development to the current applications and challenges in oral drug delivery. Pharmaceutics. 2020 Dec;12(12):1194. doi: 10.3390/pharmaceutics12121194, PMID 33317067.

24. Cherniakov I, Domb AJ, Hoffman A. Self-nano-emulsifying drug delivery systems: an update of the biopharmaceutical aspects. Expert Opin Drug Deliv. 2015 Jul 3;12(7):1121-33. doi: 10.1517/17425247.2015.999038, PMID 25556987.

25. Zafar F, Jahan N, Khalil Ur Rahman AM, Asi M, Zafar WU. Nanosuspension enhances dissolution rate and oral bioavailability of Terminalia arjuna bark extract in vivo and in vitro. Asian Pac J Trop Biomed. 2020;10(4):164. doi: 10.4103/2221-1691.280293.

26. Prihapsara F, Ifrian Wijayanti I, Budiharjo A, Pangastut A, Nur Artanti A. Characterization and antihypertensive activity of ginger extract-eel bone oil SNEDDS (self-nanoemulsifying drug delivery system). Pharm Sci Asia. 2021;48(1):90-8. doi: 10.29090/psa.2021.01.19.120.

27. Abdallah HM, El Bassossy HM, El Halawany AM, Ahmed TA, Mohamed GA, Malebari AM. Self-nanoemulsifying drug delivery system loaded with Psiadia punctulata major metabolites for hypertensive emergencies: effect on hemodynamics and cardiac conductance. Front Pharmacol. 2021;12:681070. doi: 10.3389/fphar.2021.681070, PMID 34177590.