Effect of surfactant concentration and sterilization process on intraocular pressure-lowering activity of Δ9-tetrahydrocannabinol-valine-hemisuccinate (NB1111) nanoemulsions

Corinne Sweeney; Narendar Dudhipala; Ruchi Thakkar; Tabish Mehraj; Sushrut Marathe; Waseem Gul; Mahmoud A ElSohly; Brian Murphy; Soumyajit Majumdar

doi:10.1007/s13346-020-00871-9

Effect of surfactant concentration and sterilization process on intraocular pressure-lowering activity of Δ⁹-tetrahydrocannabinol-valine-hemisuccinate (NB1111) nanoemulsions

Drug Deliv Transl Res. 2021 Oct;11(5):2096-2107. doi: 10.1007/s13346-020-00871-9. Epub 2020 Nov 9.

Authors

Corinne Sweeney¹, Narendar Dudhipala¹, Ruchi Thakkar¹, Tabish Mehraj¹, Sushrut Marathe¹, Waseem Gul^{2

3}, Mahmoud A ElSohly^{1

2

3}, Brian Murphy⁴, Soumyajit Majumdar^{5

6}

Affiliations

¹ Department of Pharmaceutics and Drug Delivery, University of Mississippi, Oxford, MS, 38677, USA.
² ElSohly Laboratories Inc, 5-Industrial Park Drive, Oxford, MS, 38655, USA.
³ National Center for Natural Products Research, University of Mississippi, Oxford, MS, 38677, USA.
⁴ Emerald Bioscience Inc, Long Beach, CA, 90803, USA.
⁵ Department of Pharmaceutics and Drug Delivery, University of Mississippi, Oxford, MS, 38677, USA. majumso@olemiss.edu.
⁶ Research Institute of Pharmaceutical Sciences, University of Mississippi, Oxford, MS, 38677, USA. majumso@olemiss.edu.

PMID: 33169348
DOI: 10.1007/s13346-020-00871-9

Abstract

The use of Δ⁹-tetrahydrocannabinol (THC) and Δ⁹-tetrahydrocannabinol-valine-hemisuccinate (THC-VHS; NB1111) has recently been investigated in the management of intraocular pressure (IOP). The current study was undertaken to develop an optimized THC-VHS-loaded nanoemulsion formulation (NE; THC-VHS-NE) that could improve the drug load and duration of activity. THC-VHS-NE formulation was prepared by homogenization followed by ultrasonication. Sesame oil, Tween®80, and Poloxamer®188 were used as the oil, surfactant, and cosurfactant, respectively. Stability of the optimized THC-VHS-NE formulation was observed at 4 °C. The IOP lowering effect of the lead formulations, commercial timolol, and latanoprost ophthalmic solutions, as well as an emulsion in Tocrisolve™ (THC-VHS-TOC), was studied in New Zealand White rabbits following topical administration. The effect of surfactant concentration and sterilization process on IOP-lowering activity was also studied. THC-VHS-NE formulations (0.5, 1.0, and 2.0% w/v) showed dose dependent duration of action. The 1.0%w/v THC-VHS-NE formulation was selected for further evaluation because of its desirable physical and chemical characteristics. THC-VHS-NE formulation prepared with 2% w/v Tween®80 exhibited a higher drop in IOP than the 0.75 and 4.0% w/v of Tween®80 containing formulations. The IOP-lowering duration was, however, similar for the formulations with 0.75 and 2.0% Tween®80, while that with 4.0% Tween®80 was shorter. THC-VHS-NE formulation produced a greater drop in IOP (p < 0.05) and a longer duration of activity compared to THC-VHS-TOC, latanoprost, and timolol. The formulation could be sterilized by filtration without impacting product attributes. Overall, the optimized THC-VHS-NE formulation demonstrated a significantly better IOP reduction profile in the test model compared to the commercial ophthalmic solutions evaluated.

Keywords: Glaucoma; IOP; Nanoemulsion; Nonpigmented rabbits; Stability; Sterilization; Tetrahydrocannabinol-valine-hemisuccinate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antihypertensive Agents / pharmacology
Antihypertensive Agents / therapeutic use
Dronabinol* / pharmacology
Intraocular Pressure*
Ophthalmic Solutions
Rabbits
Sterilization
Surface-Active Agents
Timolol
Valine

Substances

Antihypertensive Agents
Ophthalmic Solutions
Surface-Active Agents
Dronabinol
Timolol
Valine