Category: Formulation and Quality
Purpose: We have recently shown the effect of Δ9 -Tetrahydrocannabinol Valine Hemisuccinate (THC-VHS, NB1111) on the intraocular pressure (IOP). Initial formulations studied effectively reduced the IOP in rabbits to a greater extent than the marketed formulations of timolol and pilocarpine. These formulations were, however, restricted by drug loading capacity and the duration of action. Thus, the current study was undertaken to optimize the nanoemulsion (NE) formulations with increased drug loading and reduced surfactant concentrations and also increase the duration of activity by increasing retention or penetration or both.
Methods: THC-VHS-NE formulations were prepared and optimized using homogenization followed by probe sonication method. The effect of a single dose administration of optimized THC-VHS-NE formulation on the IOP profile of normotensive New Zealand white rabbits was determined. Fifty microliters of the formulations were administered to the left eye and the contralateral eye remained untreated. IOP was measured at predetermined time intervals. Further, the effect of surfactant concentration, drug loading, filtration and pH of the THC-VHS-NE formulations were studied. All animal studies were undertaken using UM IACUC approved protocols.
Results: The THC-VHS-NE formulation with drug loads of 0.5%, 1.0%, and 2.0% demonstrated a dose-dependent drop in IOP (20-25%) and duration of activity. The 1.0% formulation was selected for further trials. It was observed that increasing the surfactant concentration from 0.75 – 4% w/v had a negative effect on the IOP lowering profile. When the pH of the THC-VHS NE (1.0%) formulation was increased from 4.5 to 5.5, no significant changes were observed in the IOP profile. Similarly, no difference in IOP profile was observed between unfiltered and filtered (0.22 µm nylon) formulations.
Conclusion: The significant IOP reduction profile suggests that the THC-VHS-NE formulation could potentially be a new alternative delivery system for THC-VHS in the treatment of glaucoma.
Narendar Dudhipala– Postdoctoral research fellow, University of Mississippi, University, Mississippi
Ruchi Thakkar– Graduate Research Assistant, The University of Mississippi, University, Mississippi
Tabish Mehraj– Graduate Student, University of Mississippi, University, Mississippi
Sushrut Marathe– Mr., University of Mississippi, University, Mississippi
Iram Shahzadi– Oxford, Mississippi
Waseem Gul– Oxford, Mississippi
Mahmoud. A. Elsohly– Oxford, Mississippi
Brian Murphy– Long Beach, California
Soumyajit Majumdar– Professor and Associate Dean, Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi. Oxford, MS, University, Mississippi