Author(s):
Priyanka. J, Nalini K
Email(s):
ns.kurup@kmkcp.edu.in
DOI:
10.52711/0974-360X.2026.00664 
Address:
Priyanka. J1, Nalini K2
1Prin. K.M. Kundnani College of Pharmacy, Colaba, Mumbai, India.
2Department of Pharmaceutics, Prin. K.M. Kundnani College of Pharmacy, Colaba, Mumbai, India.
*Corresponding Author
Published In:
Volume - 19,
Issue - 10,
Year - 2026
ABSTRACT:
Spasticity is an abnormal condition characterized by prolonged muscle contraction due to injury to the brain, spinal cord or motor neurons. This causes pain and complications such as constipation, urinary tract infection etc. Conventionally Baclofen has been used as an oral tablet but due to a short half life needs frequent administration. The current research aims to formulate a sustained release ethosomal gel of baclofen that can be applied once a day in order to alleviate the spastic condition. The Hot method was used to formulate the ethosomes followed by sonication. Box Behnken method of Quality by Design (QbD) was used to optimize the ethosomes. The impact of independent variables such as lipid concentration, ethanol concentration and sonication time was observed on critical quality attributes such as particle size and entrapment efficiency. The optimized batch was found to have a particle size of 98.9nm, polydispersity index of 0.279 and entrapment efficiency of 73%. The surface morphology was observed using Transmission Electron Microscopy. Zeta potential of -30mV indicated good stability. The optimized batch was incorporated in a Carbopol gel base to obtain an Ethosomal gel with adequate viscosity and exhibited first order release kinetics. Transepidermal flux was found to be 112.5 µg/cm2/hr with a permeability coefficient of 0.071. Hen egg Chorioallantoic membrane assay (HET CAM) was performed to rule out irritancy of the ethosomal gel. The optimized ethosomal gel was found to be stable at 25ºC 65%RH for a period of three months. Thus, a stable sustained release formulation which reduced the frequency of oral administration was successfully developed for alleviating the symptoms of spasticity.
Cite this article:
Priyanka. J, Nalini K. Formulation and Optimization of Baclofen Ethosomal Gel for Transdermal Drug Delivery using the Box Behnken Design approach. Research Journal Pharmacy and Technology. 2026;19(10):4761-8. doi: 10.52711/0974-360X.2026.00664
Cite(Electronic):
Priyanka. J, Nalini K. Formulation and Optimization of Baclofen Ethosomal Gel for Transdermal Drug Delivery using the Box Behnken Design approach. Research Journal Pharmacy and Technology. 2026;19(10):4761-8. doi: 10.52711/0974-360X.2026.00664 Available on: https://rjptonline.org/AbstractView.aspx?PID=2026-19-10-40
REFERENCES:
1. Kheder A. Nair KPS. Spasticity: pathophysiology, evaluation and management. Pract Neurol. 2012; 12(5): 289–98. doi.org/10.1136/practneurol-2011-000155
2. Becker WJ. Harris CJ. Long ML. Ablett DP. Klein GM. DeForge DA. Long-term intrathecal baclofen therapy in patients with intractable spasticity. Can J Neurol Sci. 1995; 22(3): 208–17. doi.org/10.1017/S0317167100039286
3. Gilmartin R. Bruce D. Storrs BB. Abbott R. Krach L. Ward J. et al. Intrathecal baclofen for management of spastic cerebral palsy: multicenter trial. J Child Neurol. 2000; 15(2): 71–7. doi.org/10.1177/088307380001500201
4. Qureshi AZ. Shacfe H. Ilyas A. Ayaz SB. Aljamaan KY. Moukais IS. et al. Complications of intrathecal baclofen pump therapy: an institutional experience from Saudi Arabia. Healthcare. 2023; 11(21): 2820. doi.org/10.3390/healthcare11212820
5. Cleveland Clinic. What is a baclofen pump? 2025. Available from: https://my.clevelandclinic.org/health/treatments/8997-intrathecal-baclofen-pump [cited 2025 Aug 14]
6. Cho SR. Intrathecal baclofen therapy: pros and cons. Ann Rehabil Med. 2023; 47(1): 1–3. doi.org/10.5535/arm.22164
7. Ramadan D. McCrudden MTC. Courtenay AJ. Donnelly RF. Enhancement strategies for transdermal drug delivery systems: current trends and applications. Drug Deliv Transl Res. 2022; 12(4): 758–91. doi.org/10.1007/s13346-021-01026-0
8. Jeong WY. Kwon M. Choi HE. Kim KS. Recent advances in transdermal drug delivery systems: a review. Biomater Res. 2021; 25(1): 24. doi.org/10.1186/s40824-021-00226-9
9. Touitou E. Dayan N. Bergelson L. Godin B. Eliaz M. Ethosomes – novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release. 2000; 65(3): 403–18. doi.org/10.1016/S0168-3659(99)00222-9
10. CM. Ganesh G. LM. Radhakrishnan K. A review on ethosomes for transdermal application. Res J Pharm Technol. 2019; 12(7): 3133–43.
11. Maniyar MM. Deshmukh AS. Shelke SJ. Ethosomes: a carrier for transdermal drug delivery system. Asian J Pharm Res. 2022; 12(3): 225–8.
12. Jadhav PU. Gujare SG. Shende MA. Ethosomes: a novel tool for vesicular drug delivery. Asian J Pharm Res. 2024;14(1):45–52.
13. Xie J. Ji Y. Xue W. Ma D. Hu Y. Hyaluronic acid-containing ethosomes as a potential carrier for transdermal drug delivery. Colloids Surf B Biointerfaces. 2018; 172: 323–9. doi.org/10.1016/j.colsurfb.2018.08.045
14. Ahuja S. Baclofen. In: Florey K, editor. Analytical Profiles of Drug Substances. 1985;14:527–48.
15. Patekar RR. Choudhary HB. Rede SD. Formulation and evaluation of ethosomal gel and non-ethosomal gel of S. grandiflora leaves. Res J Pharm Technol. 2022; 15(3): 1029–36.
16. Mistry A. Ravikumar P. Development and evaluation of azelaic acid based ethosomes for topical delivery for the treatment of acne. Indian J Pharm Educ Res. 2016; 50(3S): 232–43. doi.org/10.5530/ijper.50.3s.32
17. Lin H. Lin L. Choi Y. Michniak-Kohn B. Development and in-vitro evaluation of co-loaded berberine chloride and evodiamine ethosomes for treatment of melanoma. Int J Pharm. 2020; 581: 119278. doi.org/10.1016/j.ijpharm.2020.119278
18. Girhepunje K. Pal R. Gevariya H. Behera A. Thirumoorthy N. Ethosomes: a novel vesicular carrier for enhanced dermal delivery of ciclopirox olamine. Pharm Lett. 2010;2(1):360–7.
19. Mishra AD. Khunt DM. Ghayal AH. Patel CN. Shah DR. Formulation and optimization of ethosomes for transdermal delivery of felodipine. Res J Pharm Technol. 2012; 5(12): 1509–17.
20. Priya S. Jyothi D. James JP. Maxwell A. Formulation and optimization of ethosomes loaded with ropinirole hydrochloride: application of quality by design approach. Res J Pharm Technol. 2020;13(9):4339–45.
21. Chavan SD. Pimpodkar NV. Kadam AS. Gaikwad P. Quality by design. Asian J Res Pharm Sci. 2016;6(1):45–50.
22. Kadam VR. Patil MP. Pawar VV. Kshirsagar S. A review on quality by design (QbD). Asian J Res Pharm Sci. 2017; 7(4): 197–204.
23. Elsayed MMA. Abdallah OY. Naggar VF. Khalafallah NM. Deformable liposomes and ethosomes as carriers for skin delivery of ketotifen. Pharm. 2007; 62(2): 133–7. doi.org/10.1007/s00228-006-0234-5
24. Bhana R. Verma A. Jain S. Development and characterization of ethosomes bearing losartan potassium for transdermal drug delivery. Int J Pharm Pharm Sci. 2013; 5(1): 35–40.
25. Bodade SS. Shaikh KS. Kamble MS. Chaudhari PD. A study on ethosomes as mode for transdermal delivery of an antidiabetic drug. Drug Deliv. 2013; 20(1): 40–6. doi.org/10.3109/10717544.2012.762432
26. Goindi S. Dhatt B. Kaur A. Ethosomes-based topical delivery system of antihistaminic drug for treatment of skin allergies. J Microencapsul. 2014; 31(7): 716–24. doi.org/10.3109/02652048.2014.915627
27. Lodzki M. Godin B. Rakou L. Mechoulam R. Gallily R. Touitou E. Cannabidiol-transdermal delivery and anti-inflammatory effect in a murine model. J Control Release. 2003; 93(3): 377–87. doi.org/10.1016/j.jconrel.2003.09.001
28. Jain S. Umamaheshwari RB. Bhadra D. Jain NK. Indian journal of pharmaceutical sciences. Indian J Pharm Sci. 2004; 66(1): 72–81.
29. Sahu SK. Ram A. Evaluation of linezolid loaded ethosomes for treatment of deep skin infections in diabetic model. Res J Pharm Technol. 2018; 11(7): 3023–30.
30. Bhulli N. Sharma A. Preparation of novel vesicular carrier ethosomes with glimepiride and their investigation of permeability. Int J Ther Appl. 2012; 2.
31. Gondkar SB. Patil NR. Saudagar RB. Formulation development and characterization of etodolac loaded transethosomes for transdermal delivery. Res J Pharm Technol. 2017; 10(9): 3049–57.
32. Sujatha S. Sowmya G. Chaitanya M. Reddy VSK. Monica M. Kumar KK. Preparation, characterization and evaluation of finasteride ethosomes. Int J Drug Deliv. 2016; 8: 1–11.
33. Paliwal S. Tilak A. Sharma J. Dave V. Sharma S. Yadav R. et al. Flurbiprofen loaded ethosomes – transdermal delivery of anti-inflammatory effect in rat model. Lipids Health Dis. 2019; 18(1): 133. doi.org/10.1186/s12944-019-1084-0
34. Kollipara RK. Tallapaneni V. Sanapalli BKR. Kumar GV. Karri VVSR. Curcumin loaded ethosomal vesicular drug delivery system for the treatment of melanoma skin cancer. Res J Pharm Technol. 2019; 12(4): 1783.
35. Silva IR. Lima FA. Reis ECO. Ferreira LAM. Goulart GAC. Stepwise protocols for preparation and use of porcine ear skin for in vitro skin permeation studies using Franz diffusion cells. Curr Protoc. 2022; 2(3): e391. doi.org/10.1002/cpz1.391
36. Zhang Y. Lane ME. Hadgraft J. Heinrich M. Chen T. Lian G. et al. A comparison of the in vitro permeation of niacinamide in mammalian skin and in the parallel artificial membrane permeation assay (PAMPA) model. Int J Pharm. 2019; 556: 142–9. doi.org/10.1016/j.ijpharm.2018.11.064
37. HET-CAM test method: ICCVAM recommended protocol. 2025. Available from: https://ntp.niehs.nih.gov/sites/default/files/iccvam/docs/protocols/ivocular-hetcam.pdf [cited 2025 Aug 9]
38. Wilson TD. Steck WF. A modified HET–CAM assay approach to the assessment of anti-irritant properties of plant extracts. Food Chem Toxicol. 2000; 38(10): 867–72. doi.org/10.1016/S0278-6915(00)00066-4
39. Anantaworasakul P. Chaiyana W. Michniak-Kohn BB. Rungseevijitprapa W. Ampasavate C. Enhanced transdermal delivery of concentrated capsaicin from chili extract-loaded lipid nanoparticles with reduced skin irritation. Pharmaceutics. 2020; 12(5): 463. doi.org/10.3390/pharmaceutics12050463
40. Bhalaria MK. Naik S. Misra AN. Ethosomes: a novel delivery system for antifungal drugs in the treatment of topical fungal diseases. Indian J Exp Biol. 2009;47(5):368–75.
41. Dave V. Bhardwaj N. Gupta N. Tak K. Herbal ethosomal gel containing luliconazole for productive relevance in the field of biomedicine. 3 Biotech. 2020; 10(3): 97. doi.org/10.1007/s13205-020-2108-6
42. Abouhussein DMN. Enhanced transdermal permeation of BCS class IV aprepitant using binary ethosome: optimization, characterization and ex vivo permeation. J Drug Deliv Sci Technol. 2021; 61: 102185. doi.org/10.1016/j.jddst.2020.102185
43. Paolino D. Lucania G. Mardente D. Alhaique F. Fresta M. Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers. J Control Release. 2005; 106(1–2): 99–110. doi.org/10.1016/j.jconrel.2005.05.001
44. Rakesh R. Anoop KR. Formulation and optimization of nano-sized ethosomes for enhanced transdermal delivery of cromolyn sodium. J Pharm Bioallied Sci. 2012; 4(4): 333–40. doi.org/10.4103/0975-7406.103257
45. Ismail TA. Shehata TM. Mohamed DI. Elsewedy HS. Soliman WE. Quality by design for development, optimization and characterization of brucine ethosomal gel for skin cancer delivery. Molecules. 2021; 26(11): 3454. doi.org/10.3390/molecules26113454
46. Pathan IB. Jaware BP. Shelke S. Ambekar W. Curcumin loaded ethosomes for transdermal application: formulation, optimization, in vitro and in vivo study. J Drug Deliv Sci Technol. 2018; 44: 49–57. doi.org/10.1016/j.jddst.2017.12.016
47. Xiang H. Xu S. Zhang W. Li Y. Zhou Y. Miao X. Skin permeation of curcumin nanocrystals: effect of particle size, delivery vehicles, and permeation enhancer. Colloids Surf B Biointerfaces. 2023; 224: 113203. doi.org/10.1016/j.colsurfb.2023.113203
48. Chourasia MK. Kang L. Chan SY. Nanosized ethosomes bearing ketoprofen for improved transdermal delivery. Results Pharma Sci. 2011; 1(1): 60–7. doi.org/10.1016/j.rps.2011.02.001
49. Aljohani AA. Alanazi MA. Munahhi LA. Hamroon JD. Mortagi Y. Qushawy M. Soliman GM. Binary ethosomes for the enhanced topical delivery and antifungal efficacy of ketoconazole. OpenNano. 2023; 11: 100145. doi.org/10.1016/j.onano.2023.100145
50. Akhtar N. Menaa F. Akhtar N. Javed N. Sethi A. Khan MS. Tocopherol succinate-loaded ethosomal gel synthesized by cold method technique: deeper biophysical characterizations for translational application on human skin. J Cosmet Dermatol. 2024; 23(3): 1015–28. doi.org/10.1111/jocd.16062