Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation.
Pharmaceutics June 11, 2025 Bernard Do, Luc Mallet, Maxime Annereau et al.
D-lysergic acid diethylamide (D-LSD), being investigated for alcohol use disorder, is extremely sensitive to light, which complicates formulation for clinical trials. A liquid-filled capsule formulation was developed to protect D-LSD from photodegradation while providing accurate dosing. Using liquid chromatography with ion mobility spectrometry and mass spectrometry, along with quantum chemical calculations, researchers characterized degradation products. Photostress studies showed that D-LSD in solution rapidly degrades into photoisomers and photooxidative byproducts, but the capsule formulation markedly reduced these transformations under ICH-compliant conditions. Orthogonal stability profiling is essential for guiding formulation development, and this capsule approach may offer a viable, photostable platform for future clinical investigation of D-LSD.