FREEZE-DRIED BINARY AND TERNARY SOLID DISPERSIONS OF CANNABIDIOL: FORMULATION, CHARACTERIZATION, AND SOLUBILITY ENHANCEMENT

Abstract

Objective: Cannabidiol (CBD) is a non-psychoactive phytocannabinoid with broad therapeutic potential. However, it’s extremely poor aqueous solubility limits pharmaceutical development. This study aimed to enhance CBD solubility using binary and ternary amorphous solid dispersions (SDs) prepared by freeze-drying. Methods: Freeze-drying conditions were optimized by screening solvent systems based on frozen-state thermal behavior. Binary SDs were prepared with polyvinylpyrrolidone (PVP-K30 or PVP-K90), while ternary SDs incorporated surfactants (TPGS, poloxamer 188, and poloxamer 407). Formulations were evaluated for solubility, dissolution, solid-state properties (DSC, FTIR), and stability. Results: The optimal solvent system was 35% (v/v) tert-butyl alcohol. Binary SDs increased CBD solubility by up to 32-fold. Initial screening of ternary systems achieved approximately 7,000-fold enhancement, with poloxamer 407 showing the greatest effect. Further optimization yielded formulations (F7 and F14) with up to ~11,000-fold increased solubility and rapid dissolution. DSC confirmed complete amorphization, while FTIR indicated intermolecular interactions. The optimized formulations maintained amorphous characteristics and>96% CBD content after six months. Conclusion: Freeze-dried ternary SDs, particularly those containing poloxamer 407, provide a robust strategy for markedly enhancing CBD solubility and dissolution with good stability.