Comparative Analysis of Loxoprofen Loaded Ethosomal Gel Formulations Incorporating Carbopol and Hydroxypropyl Methylcellulose

Main Article Content

Sarah Jabbar Abd Alhur
Hasanain Shakir Mahmood
Pegah Khosravian

Abstract

Transdermal delivery is recognized as one of 
the most advantageous non-invasive drug 
delivery technologies; but the skin's natural 
barrier, particularly the stratum corneum, 
restricts drug permeation.  However, 
ethosomes, which are phospholipid vesicles 
containing ethanol, have the potential to 
enhance transdermal drug delivery.  
They are integrated into various vehicles to create innovative pharmaceutical formulations like 
ethosomal gels (EGs). This study aimed to assess the appropriateness of various grades of carbopol 
and hydroxypropyl methylcellulose (HPMC) as gel matrices for ethosomal suspensions intended 
for transdermal delivery of loxoprofen (used as a model medication). Additionally, the effect of 
lyophilization on hydrogel was studied. Five EGs (EG1-EG5) were developed and analyzed for 
their viscosity, pH, drug content, and in vitro drug release. Additionally, the ex vivo penetration 
of EG was compared with that in a gel formed from a hydroethanolic solution of drug (Sol-G). 
The results revealed that, compared to HPMC, carbopol exhibited superior gelling properties, and 
the drug release from the lyophilized optimized EG (EG5) was much higher (95.44±0.8%) over 
12 hours than that of other formulations (p < 0.05). Moreover, the skin permeation investigation 
employing rat skin indicated that the EG5 exhibited a markedly greater flux (J) value and apparent 
permeability (Papp) in comparison to Sol-G. It can be concluded that the loxoprofen-loaded 
ethosomes were successfully formulated in gel form and can be of use for transdermal delivery.   

Article Details

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How to Cite

Comparative Analysis of Loxoprofen Loaded Ethosomal Gel Formulations Incorporating Carbopol and Hydroxypropyl Methylcellulose. (2026). Al Mustansiriyah Journal of Pharmaceutical Sciences, 25(5), 781-795. https://doi.org/10.32947/ajps.v25i5.1281

References

1. Hui M, Quan P, Yang Y, Fang L. The effect of ion-pair formation combined with penetration enhancers on the skin permeation of loxoprofen. Drug Deliv. 2016;23(5):1550-7.

2. Ryu S-R, Shin S-C. Controlled transdermal delivery of loxoprofen from an ethylene-vinyl acetate matrix. J Pharm Invest. 2011;41(6):347-54.

3. Jeong WY, Kwon M, Choi HE, Kim KS. Recent advances in transdermal drug delivery systems: A review. Biomater Res. 2021;25(1):24. DOI: https://doi.org/10.1186/s40824-021-00226-6

4. Al-Wahaab ZMA, Al-Mayahy MH. Microneedles as a potential platform for improving antibiotic delivery to bacterial infections. Heliyon. 2024;10(17): e37173. DOI: https://doi.org/10.1016/j.heliyon.2024.e37173

5. Jaiswal PK, Kesharwani S, Kesharwani R, Patel DK. Ethosome: A new technology used as topical & transdermal delivery system. J. Drug Delivery Ther. 2016;6(3):7-17. DOI: https://doi.org/10.22270/jddt.v6i3.1245

6. Jadhav PU, Gujare SG, Shende MA. Ethosomes: A novel tool for vesicular drug delivery. Asian J Pharm Sci. 2024;14(1):45-52. DOI: https://doi.org/10.52711/2231-5691.2024.00007

7. Abubakr A-H, Othman AI. Ethosomes: a potential nanocarrier for transdermal drug delivery‏. ERURJ. 2023;2(1):161-76. DOI: https://doi.org/10.21608/erurj.2023.190245.1010

8. Nugrahani HN. Stability study of azelaic acid proethosomes with lyoprotectant as stabilizer. J Adv Pharm Technol Res. 2018;9(2):61-4. DOI: https://doi.org/10.4103/japtr.JAPTR_252_18

9. Kassem MA, Aboul-Einien MH, El Taweel MM. Dry gel containing optimized felodipine-loaded transferosomes: A promising transdermal delivery system to enhance drug bioavailability. AAPS pharmscitech. 2018;19:2155-73. DOI: https://doi.org/10.1208/s12249-018-1020-5

10. Riccardi D, Baldino L, Reverchon E. Liposomes, transfersomes and niosomes: production methods and their applications in the vaccinal field. J Transl Med. 2024;22(1):339. DOI: https://doi.org/10.1186/s12967-024-05160-4

11. Bhandari S, Rathore KS. Formulation and evaluation of nano-ethogel of silver sulfadiazine for treatment of topical burns. infection. 2023;11:15. DOI: https://doi.org/10.18231/j.ijcaap.2022.038

12. Yu X, Du L, Li Y, Fu G, Jin Y. Improved anti-melanoma effect of a transdermal mitoxantrone ethosome gel. Biomed Pharmacother. 2015; 73:6-11 DOI: https://doi.org/10.1016/j.biopha.2015.05.002

13. Avasarala H, Dinakaran S, Boddeda B, Dasari SP, Jayanthi VR, Swaroopa P. Ethosomal gel: a novel choice for topical delivery of the antipsychotic drug Ziprasidone Hydrochloride. Braz. J. Pharm. Sci. 2022;58: e19317. DOI: https://doi.org/10.1590/s2175-97902022e19317

14. Fathalla D, Youssef EM, 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. DOI: https://doi.org/10.3390/pharmaceutics12050446

15. Shamma RN, Elsayed I. Transfersomal lyophilized gel of buspirone HCl: formulation, evaluation and statistical optimization. J Liposome Res. 2013;23(3):244-54. DOI: https://doi.org/10.3109/08982104.2013.801489

16. Ghareeb MM, Mohammed MS. Topical nanoemulsion-based gel of isoconazole nitrate. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2023; 23:378-396. DOI: https://doi.org/10.32947/ajps.v23i4.1093

17. Sakran W, Abdel-Rashid RS, Saleh F, Abdel-Monem R. Ethosomal gel for rectal transmucosal delivery of domperidone: design of experiment, in vitro, and in vivo evaluation. Drug Deliv. 2022;29(1):1477-91. DOI: https://doi.org/10.1080/10717544.2022.2072542

18. Mehmood Y, Shahid H, Ahmed S, Khursheed A, Jamshaid T, Jamshaid M, et al. Synthesis of vitamin D3 loaded ethosomes gel to cure chronic immune-mediated inflammatory skin disease: physical characterization, in vitro and ex vivo studies. Sci Rep. 2024;14(1):1-15. DOI: https://doi.org/10.1038/s41598-024-72951-6

19. 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. DOI: https://doi.org/10.1111/jocd.13251

20. KKHUDHAIR AS, SABRI LA. Preparation and evaluation of topical hydrogel containing ketoconazole-loaded bilosomes. Acta Pharm Sci. 2024; 62(4). DOI: https://doi.org/10.23893/1307-2080.APS6250

21. Sicurella M, Pula W, Musiał K, Cieślik-Boczula K, Sguizzato M, Bondi A, et al. Ethosomal gel for topical administration of dimethyl fumarate in the treatment of HSV-1 infections. Int J Mol Sci. 2023;24(4):4133. DOI: https://doi.org/10.3390/ijms24044133

22. Kocabaş NÖ, Kahraman E, Güngör S. Assessment of membrane type effects on in vitro performance of topical semi-solid products. Journal of Drug Delivery Science and Technology. 2021;64:102646. DOI: https://doi.org/10.1016/j.jddst.2021.102646

23. Abd Alhur SJ, Mahmood HS. Fabrication and assessment of ethosomes for effective transdermal delivery of loxoprofen. Iran J Basic Med Sci. 2025;28(6):728-38.

24. Hameed HI, Al-Mayahy MH. Combined approach of nanoemulgel and microneedle pre-treatment as a topical anticellulite therapy. ADMET and DMPK. 2024;12(6):903-23. DOI: https://doi.org/10.5599/admet.2461

25. Ibrahim TM, Abdallah MH, El-Megrab NA, El-Nahas HM. Transdermal ethosomal gel nanocarriers; a promising strategy for enhancement of anti-hypertensive effect of carvedilol. J Liposome Res . 2019;29(3):215-28. DOI: https://doi.org/10.1080/08982104.2018.1529793

26. Mamatha J, Gadili S, Pallavi K. Formulation and evaluation of zidovudine transdermal patch using permeation enhancers. J Young Pharm. 2020;12(2s):s45. DOI: https://doi.org/10.5530/jyp.2020.12s.45

27. Al-Ameri AAF, Al-Gawhari FJ. Formulation development of meloxicam binary ethosomal hydrogel for topical delivery: in vitro and in vivo assessment. Pharmaceutics. 2024;16(7). DOI: https://doi.org/10.3390/pharmaceutics16070898

28. Nser SM, Al-Shohani ADH, Abuawad A. Effect of using high molecular weight crosslinker on the physical properties of super porous hydrogel composite. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2023;23(4):355-66. DOI: https://doi.org/10.32947/ajps.v23i4.1091

29. Ghanbarzadeh S, Valizadeh H, Zakeri-Milani P. The effects of lyophilization on the physico-chemical stability of sirolimus liposomes. Adv Pharm Bull 2013;3(1):25.

30. Apriani EF, Shiyan S, Hardestyariki D, Starlista V, Sari AL. Optimization of hydroxypropyl methylcellulose (HPMC) and carbopol 940 in clindamycin HCl ethosomal gel as anti-acne. Research Journal of Pharmacy and Technology. 2024;17(2):603-11. DOI: https://doi.org/10.52711/0974-360X.2024.00094

31. Martihandini N, Surini S, Bahtiar A. Andrographolide-loaded ethosomal gel for transdermal application: Formulation and in vitro penetration study. Pharmaceutical Sciences. 2021;28(3):470-80. DOI: https://doi.org/10.34172/PS.2021.76

32. Maraie NK, Kadhium HS. Efficacy of Gelling Agents on The In Vitro Release and Physical Properties of Loxoprofen Sodium Gel Containing Ultra Elastic Vesicles. International Journal of Drug Delivery Technology. 2019;9(4):671-7. DOI: https://doi.org/10.25258/ijddt.9.4.26

33. Ansari SA, Qadir A, Warsi MH, Mujeeb M, Aqil M, Mir SR, et al. Ethosomes-based gel formulation of karanjin for treatment of acne vulgaris: in vitro investigations and preclinical assessment. 3 Biotech. 2021;11:1-14. DOI: https://doi.org/10.1007/s13205-021-02978-3

34. Shetty S, Jose J, Kumar L, Charyulu RN. Novel ethosomal gel of clove oil for the treatment of cutaneous candidiasis. J Cosmet Dermatol 2019;18(3):862-9. DOI: https://doi.org/10.1111/jocd.12765

35. Aldawsari MF, Alam A, Imran M. Rutin-loaded transethosomal gel for topical application: a comprehensive analysis of skin permeation and antimicrobial efficacy. ACS omega. 2024;9(25):27300-11. DOI: https://doi.org/10.1021/acsomega.4c01718

36. Risbud MV, Hardikar AA, Bhat SV, Bhonde RR. pH-sensitive freeze-dried chitosan–polyvinyl pyrrolidone hydrogels as controlled release system for antibiotic delivery. J Control Release. 2000;68(1):23-30. DOI: https://doi.org/10.1016/S0168-3659(00)00208-X

37. Sayed OM, Abo El-Ela FI, Kharshoum RM, Salem HF. Treatment of basal cell carcinoma via binary ethosomes of vismodegib: in vitro and in vivo studies. AAPS PharmSciTech. 2020;21:1-11. DOI: https://doi.org/10.1208/s12249-019-1574-x

38. Aljohani AA, Alanazi MA, Munahhi LA, Hamroon JD, Mortagi Y, Qushawy M, et al. Binary ethosomes for the enhanced topical delivery and antifungal efficacy of ketoconazole. OpenNano. 2023;11:100145. DOI: https://doi.org/10.1016/j.onano.2023.100145

39. Abdallah MH, Lila ASA, Unissa R, Elsewedy HS, Elghamry HA, Soliman MS. Brucine-loaded ethosomal gel: design, optimization, and anti-inflammatory activity. AAPS PharmSciTech. 2021;22(8):269. DOI: https://doi.org/10.1208/s12249-021-02113-8

40. Mohamed JMM, Khan BA, Rajendran V, El-Sherbiny M, Othman G, Hussamuldin ABA, et al. Polymeric ethosomal gel loaded with nimodipine: optimisation, pharmacokinetic and histopathological analysis. Saudi Pharm J 2022;30(11):1603-11. DOI: https://doi.org/10.1016/j.jsps.2022.09.003

41. Priya S, Shridhar P, Shekhara K, Shenthar S, Kudva SK. Tolnaftate-loaded ethosomal gel for topical delivery: formulation and in vitro evaluation. J Health Allied SciNU. 2025; 15(01): 026-031. DOI: https://doi.org/10.1055/s-0044-1787293

42. Soba SV, Babu M, Panonnummal R. Ethosomal gel formulation of alpha phellandrene for the transdermal delivery in gout. Adv Pharm Bull. 2021;11(1):137-149. DOI: https://doi.org/10.34172/apb.2021.015

43. Choi S-H, Kim S-Y, Ryoo JJ, Lee K-P. Complexation of the non-steroidal anti-inflammatory drug loxoprofen with modified and unmodified β-cyclodextrins. Journal of Inclusion Phenomena. 2001;40:139-46. DOI: https://doi.org/10.1023/A:1011175206514

44. S Saadallah MN, Almajidi YQ, Ali A. Binary ethosomal gel for enhanced transdermal delivery of tazarotene: Development, refinement, in vitro evaluation, and skin penetration investigations. Al-Rafidain J Med Sci. 2023; 5: S42-50. DOI: https://doi.org/10.54133/ajms.v5i1S.288

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