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

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.

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Funding

This work has been supported by a research grant from Emerald Bioscience, INC.

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Correspondence to Soumyajit Majumdar.

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All animal experiments conformed to the tenets of the Association for Research in Vision and Ophthalmology statement on the Use of Animals in Ophthalmic and Vision Research and followed the University of Mississippi Institutional Animal Care and Use Committee approved protocols (18-029).

Conflict of interest

This research is sponsored by Emerald Bioscience, INC, and may lead to the development of products from which W.G., M.E., and S.M. may receive income as part of licensing fees and royalties paid to the University of Mississippi. M.E. is a scientific advisor to Emerald Bioscience. B.M. was the CMO of Emerald Bioscience, Inc. No competing financial interests exist for the other authors.

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Sweeney, C., Dudhipala, N., Thakkar, R. et al. Effect of surfactant concentration and sterilization process on intraocular pressure–lowering activity of Δ9-tetrahydrocannabinol-valine-hemisuccinate (NB1111) nanoemulsions. Drug Deliv. and Transl. Res. 11, 2096–2107 (2021). https://doi.org/10.1007/s13346-020-00871-9

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  • DOI: https://doi.org/10.1007/s13346-020-00871-9

Keywords

  • Glaucoma
  • Tetrahydrocannabinol-valine-hemisuccinate
  • Nanoemulsion
  • Stability
  • Sterilization
  • IOP
  • Nonpigmented rabbits