Optimized Silk Fibroin Hydrogel Patches for Controlled Transdermal Cannabidiol Delivery: Formulation and In Vivo Safety Assessment

ABSTRACT This study explores the development of a silk fibroin (SF) hydrogel patch for transdermal cannabidiol (CBD) delivery. The CBD‐loaded SF (CBD‐SF) patches, with concentrations ranging from 0.5% w/v to 1.5% w/v, exhibited uniform thickness (~0.33 mm) and demonstrated high stability under simulated skin conditions. The incorporation of ethanol facilitated the formation of CBD microencapsulation with an optimal size range of 0.59–58.90 μm, exhibiting a bimodal particle size distribution. This dual functionality enhances skin permeation through smaller particles while enabling controlled release through bigger particles. The addition of sodium bicarbonate (NaHCO 3 ), a gas‐generating agent, accelerated the release profile by creating a hollow structure within the matrix, promoting efficient CBD diffusion. This mechanism enabled effective CBD release over an 8‐h period. Safety evaluations based on the Organization for Economic Co‐operation and Development (OECD) guidelines (No. 402, 403, 406) confirmed the patch was non‐toxic, non‐irritating, and non‐sensitizing to animal skin. Overall, the CBD‐SF patch demonstrates potential as a safe and effective transdermal delivery system for sustained CBD release and enhanced skin absorption.