3D printed solid ophthalmic formulations with Cannabidiol: preclinical evaluation and hypotensive efficacy in an animal model

Abstract

Glaucoma is an optic neuropathy that leads to irreversible visual loss, with elevated intraocular pressure (IOP) being the main modifiable risk factor. Current topical treatments have low bioavailability, the need for multiple doses, and local adverse effects that affect adherence. Cannabidiol (CBD) has hypotensive and neuroprotective properties, but its ocular application is limited by absorption barriers and rapid elimination. 3D printed ophthalmic solid dosage forms (FFOS) using MESO-PP® are proposed to optimize the sustained ocular release of CBD. For this reason, our objective is to evaluate the ocular hypotensive efficacy of CBD FFOS conveyed in 3D printed oleogels, comparing them with the reference liquid formulation (Kanbis® CBD oil) and with commercial hypotensive drugs. To this end, CBD oleogels (Kanbis® 100 mg/mL) were developed and 3D printed to obtain personalized solid devices. The study was carried out in normotensive albino rabbits. IOP was measured with a digital tonometer before and up to 8 hours after administration. Ocular tolerance was assessed by slit lamp biomicroscopy and vital stains. CBD FFOS showed no signs of toxicity and achieved significant IOP reductions, achieving average IOP decreases of 20% (-3.73 mmHg; p<0.001) and 17% (-3.32 mmHg; p<0.001) at 4 and 8 hours, respectively. The 3D-printed CBD FFOS showed an excellent ocular safety profile and a greater and longer hypotensive effect than the reference liquid formulation.