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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MDPI AG
2025-06-01
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| Online Access: | https://www.mdpi.com/1999-4923/17/6/767 |
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| author | Bernard Do Luc Mallet Maxime Annereau Danielle Libong Audrey Solgadi Florence Vorspan Muriel Paul Philippe-Henri Secretan |
| author_facet | Bernard Do Luc Mallet Maxime Annereau Danielle Libong Audrey Solgadi Florence Vorspan Muriel Paul Philippe-Henri Secretan |
| author_sort | Bernard Do |
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| description | <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. |
| format | Article |
| id | doaj-art-e1e099dcd28f4762844de46c845cd066 |
| institution | OA Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-e1e099dcd28f4762844de46c845cd0662025-08-20T02:21:50ZengMDPI AGPharmaceutics1999-49232025-06-0117676710.3390/pharmaceutics17060767Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical InvestigationBernard Do0Luc Mallet1Maxime Annereau2Danielle Libong3Audrey Solgadi4Florence Vorspan5Muriel Paul6Philippe-Henri Secretan7Clinical Pharmacy Department, Gustave Roussy Cancer Campus, 94805 Villejuif, FranceUniversité Paris-Est Créteil, DMU IMPACT, Département Médical-Universitaire de Psychiatrie et d’Addictologie, Hôpitaux Universitaires Henri Mondor-Albert Chenevier, Assistance Publique-Hôpitaux de Paris, 94000 Créteil, FranceClinical Pharmacy Department, Gustave Roussy Cancer Campus, 94805 Villejuif, FranceLip(Sys)2—Chimie Analytique Pharmaceutique, Université Paris-Saclay, 91400 Orsay, FranceUMS-IPSIT SAMM Facility, Université Paris-Saclay, Inserm, CNRS, Ingénierie et Plateformes au Service de l’Innovation Thérapeutique, 91400 Orsay, FranceUniversité Paris Cité, INSERM UMRS 1144 Optimisation Thérapeutique en Neuropharmacologie, 75006 Paris, FranceDepartment of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, FranceMatériaux et Santé, Université Paris-Saclay, 91400 Orsay, France<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.https://www.mdpi.com/1999-4923/17/6/767D-LSDphotostabilityformulation developmentorthogonal analysisLC-IM-MSDFT |
| spellingShingle | Bernard Do Luc Mallet Maxime Annereau Danielle Libong Audrey Solgadi Florence Vorspan Muriel Paul Philippe-Henri Secretan Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation Pharmaceutics D-LSD photostability formulation development orthogonal analysis LC-IM-MS DFT |
| title | Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation |
| title_full | Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation |
| title_fullStr | Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation |
| title_full_unstemmed | Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation |
| title_short | Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation |
| title_sort | stability guided formulation of a light sensitive d lsd capsule for clinical investigation |
| topic | D-LSD photostability formulation development orthogonal analysis LC-IM-MS DFT |
| url | https://www.mdpi.com/1999-4923/17/6/767 |
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