Purpose
This research aims to develop a stable Nanoemulsion formulation for a challenging, water-insoluble, and thermally, oxidatively, and photolytically unstable active pharmaceutical ingredient (API) for ophthalmic use, specifically to help reduce intraocular pressure (IOP) and provide neuroprotection. The cannabinoid API has shown great potential in treating glaucoma by targeting the endocannabinoid system (ECS) to lower IOP and provide valuable neuroprotection.
Method
The solubility of the cannabinoid in various oils was systematically assessed. Placebo trials were conducted to identify the appropriate stabilizer and its concentration. To mitigate oxidation, low peroxide-grade sesame oil, and nitrogen/argon-purged water were used throughout the process. Nanoemulsion was prepared under a nitrogen atmosphere. Reduction of particle size was accomplished utilizing a Microfluidics M110-P under optimized pressure and number of passes. Antioxidants were evaluated to inhibit the oxidation of the API. Various packaging materials were evaluated for stability.
Results
Sesame oil exhibited the most pronounced solubilizing capability for the API. Tween 80 effectively stabilized the Nanoemulsion, resulting in a particle size of approximately 150 nanometers. Treatment via a microfluidizer at a pressure of 25,000 PSI over five passes yielded the targeted particle size alongside a low polydispersity index and a narrow size distribution. The Nanoemulsion retained its particle size even after filtration through a 0.22 µm filter, experiencing minimal resistance. A synergistic combination of butylated hydroxyanisole /butylated hydroxytoluene and Vitamin A effectively mitigated the oxidation of the cannabinoid API. Containers composed of low-density polyethylene and high-density polyethylene demonstrated enhanced stability in comparison to polypropylene and amber glass containers.
Conclusion
This research proficiently formulated a stable Nanoemulsion for the ophthalmic delivery of the cannabinoid API, effectively mitigating issues related to its inadequate aqueous solubility and inherent instability. The findings provide valuable insights into the potential treatment of glaucoma using this novel Nanoemulsion formulation.
