Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, University, MS 38677, USA; Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
Int J Pharm. 2024 May 25;657:124110. doi: 10.1016/j.ijpharm.2024.124110. Epub 2024 Apr 10.
The goal of this investigation is to develop stable ophthalmic nanoformulations containing cannabidiol (CBD) and its analog cannabidiol-valine-hemisuccinate (CBD-VHS) for improved ocular delivery. Two nanoformulations, nanoemulsion (NE) and nanomicelles (NMC), were developed and evaluated for physicochemical characteristics, drug-excipient compatibility, sterilization, thermal analysis, surface morphology, ex-vivo transcorneal permeation, corneal deposition, and stability. The saturation solubility studies revealed that among the surfactants tested, Cremophor EL had the highest solubilizing capacity for CBD (23.3 ± 0.1 mg/mL) and CBD-VHS (11.2 ± 0.2 mg/mL). The globule size for the lead CBD formulations (NE and NMC) ranged between 205 and 270 nm while CBD-VHS-NMC formulation had a particle size of about 78 nm. The sterilized formulations, except for CBD-VHS-NMC at 40 °C, were stable for three months of storage (last time point tested). Release, in terms of CBD, in the in-vitro release/diffusion studies over 18 h, were faster from the CBD-VHS nanomicelles (38 %) compared to that from the CBD nanoemulsion (16 %) and nanomicelles (33 %). Transcorneal permeation studies revealed improvement in CBD permeability and flux with both formulations; however, a greater improvement was observed with the NMC formulation compared to the NE formulation. In conclusion, the nanoformulations prepared could serve as efficient topical ocular drug delivery platforms for CBD and its analog.
本研究旨在开发含有大麻二酚 (CBD) 及其类似物大麻二酚-缬氨酸-半琥珀酸酯 (CBD-VHS) 的稳定眼科纳米制剂,以改善眼部递药。本文制备了两种纳米制剂,即纳米乳剂 (NE) 和纳米胶束 (NMC),并对其理化性质、药物赋形剂相容性、灭菌、热分析、表面形态、体外角膜渗透、角膜沉积和稳定性进行了评价。饱和溶解度研究表明,在所测试的表面活性剂中,Cremophor EL 对 CBD(23.3±0.1mg/mL)和 CBD-VHS(11.2±0.2mg/mL)具有最高的增溶能力。主导 CBD 制剂(NE 和 NMC)的粒径在 205nm 到 270nm 之间,而 CBD-VHS-NMC 制剂的粒径约为 78nm。除 40°C 下的 CBD-VHS-NMC 制剂外,经灭菌的制剂在三个月的储存期内(最后一次检测时间点)均稳定。在 18 小时的体外释放/扩散研究中,CBD-VHS 纳米胶束(38%)的 CBD 释放速度快于 CBD 纳米乳剂(16%)和纳米胶束(33%)。角膜渗透研究表明,两种制剂均可提高 CBD 的渗透性和通量;然而,与 NE 制剂相比,NMC 制剂的改善更为显著。综上所述,所制备的纳米制剂可作为 CBD 及其类似物的高效眼部局部递药平台。
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