Biocompatible Water-Soluble Hydroxypropyl-β-Cyclodextrin/Cannabidiol Powder Formulated via Spray Drying

Abstract

The poor aqueous solubility and instability of cannabidiol (CBD) limit its effectiveness in food, nutraceutical, and pharmaceutical applications, creating a pressing need for advanced delivery systems. This study addresses this challenge by developing a water-soluble CBD powder formulation through complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD). Phase solubility studies revealed that HP-β-CD significantly enhances CBD’s solubility (1:1 stoichiometry), while spray-dried HP-β-CD/CBD complexes exhibited improved thermal stability and physicochemical properties. Comprehensive characterization─using SEM, FTIR, Raman, XRD, NMR, and molecular docking─confirmed stable inclusion complex formation and elucidated the encapsulation mechanism. Importantly, biocompatibility testing on human bone marrow mesenchymal stem cells (h-BM-MSCs) demonstrated concentration-dependent effects on cell viability, underscoring the relevance of safety assessment for future applications. These findings establish HP-β-CD complexation as a scalable, cost-effective strategy to optimize CBD’s functionality, enabling the development of safer and more effective CBD-enriched products for diverse industries.