Formulation and Evaluation of Caffeine-Loaded Cubosomes Hydrogel for Topical Delivery

Authors

  • Arjun L Uppar Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India https://orcid.org/0009-0002-3780-4689
  • Chandrashekar C. Patil Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India
  • Shashank Namannavar Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India https://orcid.org/0009-0007-6653-4098
  • Pankaj Ajit Deshmane Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India https://orcid.org/0009-0008-4724-3807

Abstract

The goal of the current study was to create and assess a cubosomal hydrogel loaded with caffeine for long-term topical administration. Due to its hydrophilic nature, caffeine, which is widely utilized for its antioxidant, lipolytic, and skin-stimulating qualities, has limited skin permeability in traditional formulations. Glyceryl monooleate (GMO) and Poloxamer 407 were used in the top-down procedure to create cubosomes in order to get over this restriction. Particle size, polydispersity index (PDI), zeta potential, morphology, entrapment efficiency, and compatibility tests were assessed for the produced formulations. With a particle size of 280.4 nm, a PDI of 0.3461, and a zeta potential of −23.64 mV, F3 demonstrated the best qualities among the produced formulations, indicating satisfactory stability. F3's entrapment efficiency was determined to be 88.915 ± 0.148%. After being integrated into a Carbopol 934 hydrogel, the improved cubosomal dispersion was assessed for physicochemical characteristics. The gel had an appropriate pH of 6.72 ± 0.48, a viscosity of 13285 ± 6.12 cps, good spreadability, a consistent drug content of 95.382 ± 0.864%, and no grittiness. Caffeine was shown to be released continuously for up to 24 hours (82.756%), in-vitro drug release tests using Franz diffusion cells, which followed Higuchi diffusion kinetics. Formulation parameters did not significantly change throughout 90-day stability testing. Overall, the findings point to cubosomal hydrogel filled with caffeine as a potential method for improved and long-lasting topical medication administration.

Keywords: Caffeine; Cubosomes; Topical drug delivery; Carbopol hydrogel; Sustained release

Keywords:

Caffeine, Cubosomes, Topical drug delivery, Carbopol hydrogel, Sustained Release

DOI

https://doi.org/10.22270/jddt.v16i4.7666

Author Biographies

Arjun L Uppar, Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India

Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India

Chandrashekar C. Patil, Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India

Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India

Shashank Namannavar, Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India

Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India

Pankaj Ajit Deshmane, Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India

Department of Pharmaceutics, BLDEA'S Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura, Karnataka, India

References

1. Raina N, Rani R, Thakur VK, Gupta M. New insights in topical drug delivery for skin disorders: from a nanotechnological perspective. ACS omega. 2023 May 19;8(22):19145-67. https://doi.org/10.1021/acsomega.2c08016

2. Sivadasan D, Sultan MH, Alqahtani SS, Javed S. Cubosomes in drug delivery—a comprehensive review on its structural components, preparation techniques and therapeutic applications. Biomedicines. 2023 Apr 7;11(4):1114. https://doi.org/10.3390/biomedicines11041114

3. Ősz BE, Jîtcă G, Ștefănescu RE, Pușcaș A, Tero-Vescan A, Vari CE. Caffeine and its antioxidant properties—it is all about dose and source. International journal of molecular sciences. 2022 Oct 28;23(21):13074. https://doi.org/10.3390/ijms232113074

4. Ho TC, Chang CC, Chan HP, Chung TW, Shu CW, Chuang KP, Duh TH, Yang MH, Tyan YC. Hydrogels: properties and applications in biomedicine. Molecules. 2022 May 2;27(9):2902. https://doi.org/10.3390/molecules27092902

5. Beena P, Shithin Ann Varghese, Jinny Ann Alexander, Steffy P Raju, Sherin Koshy, Feba Elsa Mathew, Elessy Abraham. Formulation and Evaluation of Cubosomal Gel of an Anti-inflammatory Agent. Research J. Pharm. and Tech. 2021; 14(2):857-862. https://doi.org/10.5958/0974-360X.2021.00152.9

6. Elnaggar Y, Etman S, Abdelmonsif D, Abdallah O. Novel piperine-loaded Tween-integrated monoolein cubosomes as brain-targeted oral nanomedicine in Alzheimer’s disease: pharmaceutical, biological, and toxicological studies. International Journal of Nanomedicine. 2015 Aug;5459. https://doi.org/10.2147/IJN.S87336

7. Maha KA Khalifa. Miconazole Nitrate based cubosome hydrogels for topical application. ijdd [Internet]. 2015 Mar. 31 [cited 2026 Feb. 25];7(1):1-12.

8. Samia M O, Aliaa I, Kariman D H, Sara H D. Formulation and evaluation of cubosomes as skin retentive system for topical delivery of clotrimazole. Jour.Adv.Pharm.Res .2019; 3 (2) : 68-82. https://doi.org/10.21608/APRH.2019.9839.1079

9. Karthika V T, Sheri P S, Kuriachan M A. Fabrication and evaluation of ketoprofen loaded cubogel for topical sustained delivery. IJRR .2018; 5(8): 149-159

10. Ananda K C, Madhubabu A, Padmanabha R A, Vasudha B, Vinod K Y. Design formulation in-vitro and ex-vivo evaluation of atazanavir oaded cubosomal gel. Biointer. Res. in App. Che.2021; 11(4): 12037-12054. https://doi.org/10.33263/BRIAC114.1203712054

11. Sinar S, Mostafa A M, Mohamed M A, Omnia M K. Cubogel as potential platform for glaucoma management. Drug Deliv. 2021; 28 (1): 293-305. https://doi.org/10.1080/10717544.2021.1872740 PMid:33509004 PMCid:PMC7850357

12. Ankit A, Prakash G, Vedamurthy J. Development and characterization of prolonged release timolol maleate cubosomal gel for ocular drug delivery. APJ. 2019; 4(1):1-14. https://doi.org/10.31024/apj.2019.4.1.1

13. Sachin K P, Atul K, Sandip B, Shitalkumar P. Formulation and evaluation of an insitu gel for ocular drug delivery of anticonjunctival drug. Cellu. Chem. Technol. 2015; 49(1): 35-40.

14. Mitkari BV, Korde SA, Mahadik KR and Kokare CR: Formulation and evaluation of topical liposomal gel for fluconazole. Indian J Pharm Educ Res 2010; 44: 324-333.

15. Sabale V, Kunjwani H and Sabale P: Formulation and in-vitro evalua-tion of the topical antiageing preparation of the fruit of Beninca sahispida. JAIM 2011; 2(3): 124-8.

16. Archana A, Vijayasri K, Madhurim M and Kumar CA: Curcumin loaded nano cubosomal hydrogel: Preparation, in-vitro characteri-zation and antibacterial activity. ChemSci Trans 2015; 4(1): 75-80.

17. Venkatesh B, Indira S and Srinivas P: Formulation and evaluation of miconazole nitrate as a cubosomal topical gel. J Glob Trends Pharm Sci 2014; 5(4): 2037-47

18. Omar S, Ismail A, Hassanin K and Hamdy S: Formulation and evaluation of cubosomes as skin retentive system for topical delivery of clotrimazole. Journal of Advanced Pharmacy Research 2019; 3(2): 68-82.

19. Ahmed MM, Fatima F, Anwer MK, Ibnouf EO, Kalam MA, Alshamsan A, Aldawsari MF, Alalaiwe A and Ansari MJ: Formulation and in-vitro evaluation of topical nanosponge-based gel containing butenafine for the treatment of fungal skin infection. Saudi Pharmaceutical Journal 2021; 29(5): 467-77.

20. González-González O, Ramirez IO, Ramirez BI, O’Connell P, Ballesteros MP, Torrado JJ, et al. Drug Stability: ICH versus Accelerated Predictive Stability Studies. Pharmaceutics. 2022 Oct 28;14(11):2324. https://doi.org/10.3390/pharmaceutics14112324

Published

2026-04-15
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How to Cite

1.
Uppar AL, Patil CC, Namannavar S, Deshmane PA. Formulation and Evaluation of Caffeine-Loaded Cubosomes Hydrogel for Topical Delivery. J. Drug Delivery Ther. [Internet]. 2026 Apr. 15 [cited 2026 Apr. 18];16(4):39-47. Available from: https://jddtonline.info/index.php/jddt/article/view/7666

How to Cite

1.
Uppar AL, Patil CC, Namannavar S, Deshmane PA. Formulation and Evaluation of Caffeine-Loaded Cubosomes Hydrogel for Topical Delivery. J. Drug Delivery Ther. [Internet]. 2026 Apr. 15 [cited 2026 Apr. 18];16(4):39-47. Available from: https://jddtonline.info/index.php/jddt/article/view/7666