(T1230-03-20) Development of Stable Nanoemulsion Formulation as an Ophthalmic Drug Delivery System for Cannabinoids

Purpose: This study is aimed at developing a nanoemulsion formulation of a poorly water-soluble and thermally, oxidatively, and photolytically unstable active pharmaceutical ingredient (API) for ophthalmic application, specifically for the reduction of intraocular pressure (IOP) and to provide neuroprotection. The API is a cannabinoid and has shown promise in glaucoma treatment by targeting the endocannabinoid system (ECS) to lower IOP and provide neuroprotection.

Methods: The solubility of cannabinoid in various oils was evaluated, and sesame oil was identified as the optimal solubilizer. Placebo trials determined the suitable stabilizer and its concentration. To mitigate oxidation, low peroxide-grade sesame oil, and nitrogen/argon-purged water were utilized during formulation processing. The Nanoemulsion was prepared under a nitrogen blanket. Particle size reduction was achieved using a Microfluidics M110-P at optimized pressure and passes. Antioxidants were explored to prevent API oxidation. Finally, different packaging materials were assessed for stability.

Results: Sesame oil demonstrated the highest solubilizing capacity for the cannabinoid API. Tween 80 effectively stabilized the nanoemulsion, achieving a particle size of approximately 150 nm. Microfluidizer treatment at 25,000 PSI for 5 passes resulted in the desired particle size with a low polydispersity index (PDI) and narrow size distribution. The nanoemulsion maintained particle size even after filtration through a 0.22 µm filter, with minimal resistance. A combination of BHA/BHT and Vitamin A successfully prevented cannabinoid API oxidation during storage. LDPE and HDPE containers exhibited superior stability compared to PP and amber glass containers.

Conclusion: In conclusion, this study successfully developed a stable nanoemulsion formulation for the ophthalmic application of the cannabinoid API, addressing its poor water solubility and instability. The findings provide valuable insights into the potential treatment of glaucoma using this nanoemulsion formulation.

Microfluidics process optimization parameters

Freeze thaw stability of the final Nanoemulsion