Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation.
Bernard Do, Luc Mallet, Maxime Annereau, Danielle Libong, Audrey Solgadi, Florence Vorspan, Muriel Paul, Philippe-Henri Secretan
Pharmaceutics June 11, 2025 DOI: 10.3390/pharmaceutics17060767 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical formulation development study Peer reviewed |
|---|---|
| Topics | LSD |
| Keywords | Dft Lc-im-ms Degradation products Formulation development Orthogonal analysis Photostability Stable drug formulation Analytical chemistry D-LSD Therapeutics |
| Key points | A liquid-filled capsule formulation markedly mitigates photodegradation of D-LSD under ICH-compliant conditions, offering a photostable platform for clinical investigation. |
Abstract
Background/Objectives: D-lysergic acid diethylamide (D-LSD) is under investigation as a potential therapeutic strategy for alcohol use disorder (AUD). However, the extreme light sensitivity of D-LSD presents a significant challenge in developing suitable pharmaceutical forms, particularly for clinical trial settings. This study proposes a liquid-filled capsule formulation designed to provide accurate dosing while protecting D-LSD from photodegradation.
Methods: To support formulation development and ensure its suitability as an investigational medicinal product, a multi-tiered analytical strategy was employed. This included liquid chromatography coupled with ion mobility spectrometry and mass spectrometry (LC-IM-MS), along with quantum chemical calculations (density functional theory (DFT) and time dependent-DFT (TD-DFT)), to ensure robust and orthogonal structural characterization of degradation products.
Results: Photostress studies demonstrated that while D-LSD in solution rapidly degrades into photoisomers and photooxidative byproducts, the capsule formulation markedly mitigates these transformations under ICH-compliant conditions.
Conclusions: These findings highlight the essential role of orthogonal stability profiling in guiding formulation development and demonstrate that this approach may offer a viable, photostable platform for future clinical investigation of D-LSD in the treatment of AUD.