2019 Mississippi IDeA Conference

Sterilization of Δ⁹–Tetrahydrocannabinol Valine Hemisuccinate (THC-VHS) loaded nanoemulsions for topical ophthalmic applications

Corinne Sweeney¹, Ruchi Thakkar¹, Tabish Mehraj¹, Sushruth Marathe¹, Narendar Dudhipala¹, Waseem Gul², Mahmoud. A. ElSohly^1,2,3, Brian Murphy⁴, Soumyajit Majumdar^{1 3}

¹Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS

²ElSohly Laboratories Inc., Oxford, MS

³Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS

⁴Emerald Bioscience Inc., Long Beach, CA

Glaucoma is a sight-threatening disease that damages the optic nerve, through the buildup of aqueous humor which results in increased intraocular pressure (IOP), that can lead to vision loss. We have recently shown, using the rabbit model, that Δ⁹–Tetrahydrocannabinol Valine Hemisuccinate (THC-VHS) effectively lowers the IOP following topical instillation. The initial formulations studied were more effective than the marketed formulations of Timolol and Pilocarpine in the reduction of IOP. Although our optimized formulation were very effective, ophthalmic formulations need to be sterile. Thus, a key objective was to study the effect of the sterilization process on the physical and chemical stability of the formulations. THC-VHS was incorporated into the previously optimized nanoemulsion (NE), or Carbopol containing NE (NEC), formulations following hot homogenization followed by probe sonication protocols. The NE and NEC formulations were subjected to two sterilization techniques: filtration using a stainless steel 13 mm filter housing and filter membrane, or, steam sterilization (autoclaving). NE THC-VHS was successfully sterilized by filtration, whereas NEC THC-VHS could be autoclaved after a slight modification to the original formulation. IOP lowering activity, in normotensive rabbits, of the pre- and post-sterilization NE and NEC formulations, did not show any significant difference (p<0.05) in terms of duration of activity or maximum drop in intensity (E_max) or time to E_max (T_max).