Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation

• Published in: AAPS PharmSciTech 2024-05, Vol.25 (5), p.112, Article 112
• Main Authors: Saini, Shagun, Soni, Bindu, Kaur, Manjot, Thakur, Shubham, Shivgotra, Riya, Shahtaghi, Navid Reza, Jain, Subheet Kumar
• Format: Article
• Language: English
• Subjects: Acute Pain - drug therapy; Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Chemistry, Pharmaceutical - methods; Drug Compounding - methods; Etodolac - administration & dosage; Etodolac - chemistry; Etodolac - pharmacokinetics; Male; Mice; Permeability; Pharmacology/Toxicology; Pharmacy; Rats; Rats, Sprague-Dawley; Research Article; Skin - drug effects; Skin - metabolism; Skin Absorption - physiology
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-024-02807-9

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action. Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro , ex vivo , and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30 ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24 min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42 cm/h for rat skin, 13.64 cm/h for mice skin, and 18.97 cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns. Graphical Abstract