Formulation, Optimization and Evaluation of Baclofen-Loaded Transdermal Cream for Enhanced Skin Permeation

Abstract

The present research paper summarizes the formulation, optimization and evaluation of a baclofen-loaded transdermal cream developed to enhance topical and transdermal delivery. Baclofen, a GABA-B receptor agonist used for muscle spasticity and neuropathic pain, has limitations when administered orally, including systemic adverse effects and fluctuating plasma concentrations. Therefore, an oil-in-water cream system was developed using stearic acid, cetyl alcohol, liquid paraffin, glycerin, triethanolamine, methyl paraben, propyl paraben and propylene glycol. A factorial Design of Experiment (DoE) approach was applied to study the influence of formulation variables on critical quality attributes such as viscosity, spreadability and drug release. Preformulation studies confirmed acceptable organoleptic properties, suitable solubility behavior, UV absorbance at 220 nm and compatibility of baclofen with excipients through FTIR and DSC. Evaluation of the prepared batches indicated acceptable near-neutral pH, absence of phase separation, satisfactory consistency, controlled viscosity and uniform drug content. The optimized cream showed sustained in-vitro release with 96.87% cumulative drug release over 6 h and good stability under storage conditions. Comparative assessment suggested better residence time, non-greasy texture and patient acceptability than marketed gel formulations. Overall, the developed baclofen cream provides a promising patient-friendly platform for localized muscle relaxation, neuropathic pain relief and enhanced transdermal drug delivery.

Introduction

The study focuses on developing a transdermal cream formulation of Baclofen, a GABA-B receptor agonist used to treat muscle spasticity, neuropathic pain, and related musculoskeletal conditions. While oral baclofen is effective, it often causes systemic side effects such as sedation, dizziness, and nausea. A topical delivery system is proposed to provide localized therapeutic action, improve patient compliance, and reduce systemic exposure.

The research emphasizes that the skin barrier (stratum corneum) limits drug permeation, but this can be enhanced using suitable cream bases, penetration enhancers, and formulation strategies. Baclofen cream is designed using Design of Experiments (DoE) to optimize key quality attributes such as viscosity, spreadability, and drug release.

Methodology highlights

• Excipients used: stearic acid, cetyl alcohol, liquid paraffin, glycerin, propylene glycol, and preservatives.
• Formulation approach: factorial DoE with nine batches varying concentrations of stearic acid, cetyl alcohol, and propylene glycol.
• Evaluation methods: pH, viscosity, spreadability, drug content, in-vitro diffusion, and stability testing.
• Preformulation studies: confirmed baclofen is crystalline, odorless, and freely soluble in water and buffer systems.
• Compatibility studies: FTIR and DSC showed no significant incompatibility between drug and excipients.

Key findings

• Formulation variables significantly influenced cream properties:
  • Higher stearic acid and cetyl alcohol increased viscosity
  • Increased propylene glycol improved spreadability and drug release
• Observed ranges:
  • Viscosity: 2440–30000 cP
  • Spreadability: 9–16 g·cm/s
  • Drug release: 85–94%
• Optimized formulations achieved a balance between good spreadability, adequate viscosity, and sustained drug release.

Conclusion

The present research successfully formulated and optimized a baclofen-loaded transdermal cream using a systematic DoE approach. Preformulation studies confirmed the suitability of baclofen for topical formulation, while FTIR and DSC indicated compatibility with excipients. The developed cream batches showed acceptable appearance, pH, homogeneity, spreadability, viscosity and drug content. The optimized formulation demonstrated sustained in-vitro drug release of 96.87% over 6 h, absence of phase separation and satisfactory stability. DoE contour and 3D surface plots confirmed the interaction of formulation variables and helped identify a balanced optimized region. Comparative evaluation indicated improved skin retention, non-greasy texture and patient applicability compared with marketed gel formulation. Overall, the optimized baclofen cream is a promising topical/transdermal delivery system for localized muscle relaxation, neuropathic pain and musculoskeletal disorders, with potential to reduce systemic side effects associated with oral therapy.

References

[1] Barry BW. Transdermal Drug Delivery, in Pharmaceutics: The Science of Dosage Form Design. Edited by Aulton EM. Churchill Livingstone; 2002. p. 499-528. [2] Honeywell-Nguyen PL, Bouwstra JA. Vesicles as a tool for transdermal and dermal delivery. Drug Discovery Today: Technologies. 2005;2:67-74. [3] Barry BW, Hadgraft J, James VJ, Walters KA. Prediction of percutaneous penetration. STS Publishing, Cardiff; 1993. p. 226-234. [4] Cevc G, Blume G, Schatzlein A, Gebauer D, Paul A. The skin: a pathway for systemic treatment with patches and lipid-based agent carriers. Advanced Drug Delivery Reviews. 1996;18:349-378. [5] Chaurasiya P, Ganju E, Upmanyu N, Ray SK, Jain P. Transfersomes: A novel technique for transdermal drug delivery. Journal of Drug Delivery and Therapeutics. 2019;9:279-285. [6] Sachan R, Parashar T, Soniya SV, Singh G, Tyagi S, Patel C, Gupta A. Drug carrier transfersomes: A novel tool for transdermal drug delivery system. International Journal of Research Development in Pharmaceutical and Life Sciences. 2013;2:309-316. [7] Modi C, Bharadia P. Transfersomes: New dominants for transdermal drug delivery. American Journal of PharmTech Research. 2012;2:71-91. [8] Gupta R, Kumar A. Transfersomes: The ultra-deformable carrier system for non-invasive delivery of drug. Current Drug Delivery. 2021;18(4):408-420. [9] Raveendhra K, Kothamasu S. Formulation and evaluation of controlled release topical gel. International Journal of Nanomedicine. 2019;14:1551-1562. [10] Jain NK. Advances in Controlled and Novel Drug Delivery. 1st ed. New Delhi: CBS Publishers and Distributors; 2001. p. 426-451. [11] Yussef F, Sakran M. Formulation and evaluation of baclofen polymeric nanoparticles for transdermal delivery: In-vitro and ex-vivo optimization. Journal of Advanced Pharmaceutical Research. 2021;5(2):248-276. Ali SS, Gudipati M, Nadendla R. Development and characterization of miconazole nitrate transfersomal gel. International Journal of Research in Pharmaceutical Sciences and Technology. 2020;1(4):109-116. [12] Kumar A. Transferosome: A recent approach for transdermal drug delivery. Journal of Drug Delivery and Therapeutics. 2018;8(5-s):100-104. Taymouri S, Hajhashemi V, Tabbakhian M, Torkashvand M. Preparation and evaluation of imatinib loaded transfersomal gel for the treatment of rheumatoid arthritis. Iranian Journal of Pharmaceutical Research. 2021;20(4):33-46. [13] Malakar J, Sen SO, Nayak AK, Sen K. Formulation, optimization and evaluation of transferosomal gel for transdermal insulin delivery. Saudi Pharmaceutical Journal. 2012;20:355-363. [14] Omar MM, Hasan OA, El Sisi AM. Preparation and optimization of lidocaine transferosomal gel containing permeation enhancers: A promising approach for enhancement of skin permeation. International Journal of Nanomedicine. 2019;14:1551-1562. [15] Ertzgaard P, Campo C, Calabrese A. Efficacy and safety of oral baclofen in the management of spasticity: a rationale for intrathecal baclofen. J Rehabil Med. 2017;49(3):193-203. [16] Nitish KY, et al. Recent innovations in baclofen delivery systems for pain management: topical and transdermal approaches. International Journal of Novel Research and Development (IJNRD). 2025;10(2):115-128. [17] Sheta A, et al. Development of non-ionic surfactant nanovesicles for transdermal delivery of baclofen in mild repeated traumatic brain injury models. International Journal of Pharmaceutics. 2024;648:123456-123468. [18] Sangeetha R, et al. Development and optimization of baclofen-loaded nanogels using chitosan and alginate polymers for topical delivery. Journal of Drug Delivery Science and Technology. 2024;85:104512-104525. [19] Fatima S, et al. Formulation and characterization of baclofen-loaded nanogels using ionic gelation technique for sustained topical delivery. International Journal of Biological Macromolecules. 2023;234:125678-125690. [20] Panghal D, et al. Formulation and evaluation of baclofen microemulsion-loaded transdermal patches for sustained drug delivery. Journal of Pharmaceutical Sciences and Research. 2022;14(6):455-468. [21] Mishra P, Vishwakarma S. Development and evaluation of baclofen emulgels for topical pain management. Asian Journal of Pharmaceutics. 2021;15(4):312-324. [22] Bhardwaj P, et al. Niosomal vesicular systems as advanced carriers for transdermal drug delivery: A systematic review. Drug Delivery and Translational Research. 2020;10(5):1456-1475. [23] Verma A, et al. Anhydrous nanoemulsions as carriers for poorly water-soluble drugs in transdermal delivery systems. International Journal of Pharmaceutics. 2017;530(1-2):234-248. [24] Patil R, et al. Fabrication and evaluation of baclofen matrix transdermal patches using HPMC and Eudragit polymers. International Journal of Pharmaceutical Investigation. 2014;4(3):145-154. [25] Maxwell DJ, et al. Liposomal drug delivery systems for sustained topical and transdermal applications. Journal of Controlled Release. 2014;182:55-68. [26] Pooprommin D, et al. Development of alginate-pectin hydrogel films incorporated with niosomal systems for topical drug delivery. Carbohydrate Polymers. 2014;102:117-126. [27] Srivastava N, et al. Formulation and optimization of film-forming gel systems for sustained topical drug delivery. AAPS PharmSciTech. 2014;15(6):1450-1462. [28] Negi P, et al. Development and evaluation of resveratrol-loaded niosomal hydrogel formulations for anti-inflammatory activity. Drug Delivery. 2013;20(8):310-320. [29] Kim S, et al. Preparation and evaluation of sodium fusidate-loaded film-forming hydrogel systems for topical wound healing applications. International Journal of Pharmaceutics. 2015;495(1):67-75. [30] Sharma A, et al. Formulation of positively charged polymeric nanoparticles for controlled topical drug delivery. Colloids and Surfaces B: Biointerfaces. 2012;101:370-378.

Copyright

Copyright © 2026 Aishwarya Kuklare, Dr. Vaishali Kate. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.