Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation

Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation

<b>Background/Objectives:</b> 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, part...

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Main Authors: Bernard Do, Luc Mallet, Maxime Annereau, Danielle Libong, Audrey Solgadi, Florence Vorspan, Muriel Paul, Philippe-Henri Secretan
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Pharmaceutics
Subjects:
D-LSD
photostability
formulation development
orthogonal analysis
LC-IM-MS
DFT
Online Access:https://www.mdpi.com/1999-4923/17/6/767
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Summary:<b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.
ISSN:1999-4923

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