Department of Pharmaceutics and Drug Delivery, University of Mississippi, Oxford, MS, 38677, USA.
ElSohly Laboratories Inc, 5-Industrial Park Drive, Oxford, MS, 38655, USA.
Drug Deliv Transl Res. 2021 Oct;11(5):2096-2107. doi: 10.1007/s13346-020-00871-9. Epub 2020 Nov 9.
The use of Δ-tetrahydrocannabinol (THC) and Δ-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.
最近，人们研究了 Δ-四氢大麻酚（THC）和 Δ-四氢大麻酚-缬氨酸-半琥珀酸酯（THC-VHS；NB1111）在管理眼内压（IOP）方面的作用。本研究旨在开发一种优化的 THC-VHS 负载纳米乳液制剂（NE；THC-VHS-NE），以提高药物载药量和作用持续时间。THC-VHS-NE 制剂通过匀浆随后超声处理制备。芝麻油、吐温®80 和泊洛沙姆 188 分别用作油、表面活性剂和助表面活性剂。观察到优化的 THC-VHS-NE 制剂在 4°C 时的稳定性。在新西兰白兔中，通过局部给药研究了先导制剂、商业噻吗洛尔和拉坦前列素滴眼液以及 Tocrisolve™中的乳液（THC-VHS-TOC）的降眼压效果。还研究了表面活性剂浓度和灭菌过程对降眼压活性的影响。THC-VHS-NE 制剂（0.5、1.0 和 2.0%w/v）显示出剂量依赖性作用持续时间。由于其理想的物理和化学特性，选择 1.0%w/v THC-VHS-NE 制剂进行进一步评估。含有 2%w/v 吐温®80 的 THC-VHS-NE 制剂显示出比含有 0.75%和 4.0%w/v 吐温®80 的制剂更高的眼压下降。然而，0.75%和 2.0%吐温®80 制剂的眼压降低持续时间相似，而 4.0%吐温®80 制剂的持续时间较短。与 THC-VHS-TOC、拉坦前列素和噻吗洛尔相比，THC-VHS-NE 制剂能更显著地降低眼压（p<0.05）并延长作用持续时间。该制剂可通过过滤进行灭菌，而不会影响产品特性。总体而言，与评估的商业眼用溶液相比，优化的 THC-VHS-NE 制剂在测试模型中表现出显著更好的眼压降低谱。
