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Extraction of Plant-based Capsules for Microencapsulation Applications
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Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation.

Bernard Do1,2, Luc Mallet3,4,5, Maxime Annereau1,2

  • 1Clinical Pharmacy Department, Gustave Roussy Cancer Campus, 94805 Villejuif, France.

Pharmaceutics
|June 27, 2025
PubMed
Summary
This summary is machine-generated.

A new liquid-filled capsule protects D-lysergic acid diethylamide (D-LSD) from light, addressing a key challenge for its use in treating alcohol use disorder (AUD). This photostable formulation is crucial for future clinical trials.

Keywords:
D-LSDDFTLC-IM-MSdegradation productsformulation developmentorthogonal analysisphotostability

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Area of Science:

  • Pharmaceutical Sciences
  • Medicinal Chemistry
  • Analytical Chemistry

Background:

  • D-lysergic acid diethylamide (D-LSD) shows therapeutic potential for alcohol use disorder (AUD).
  • D-LSD's extreme photosensitivity hinders pharmaceutical development and clinical applications.
  • Developing a photostable D-LSD formulation is critical for its advancement as an investigational medicinal product.

Purpose of the Study:

  • To develop and characterize a liquid-filled capsule formulation of D-LSD.
  • To protect D-LSD from photodegradation during storage and handling.
  • To ensure accurate dosing and suitability for clinical trials in AUD treatment.

Main Methods:

  • Utilized a multi-tiered analytical strategy including liquid chromatography coupled with ion mobility spectrometry and mass spectrometry (LC-IM-MS).
  • Employed quantum chemical calculations (DFT and TD-DFT) for structural characterization of degradation products.
  • Conducted photostress studies under ICH-compliant conditions to assess formulation stability.

Main Results:

  • D-LSD in solution rapidly degrades into photoisomers and photooxidative byproducts when exposed to light.
  • The proposed liquid-filled capsule formulation significantly mitigated D-LSD photodegradation.
  • Orthogonal stability profiling confirmed the photoprotective efficacy of the capsule.

Conclusions:

  • The developed capsule formulation offers a viable, photostable platform for D-LSD.
  • Orthogonal stability profiling is essential for guiding pharmaceutical formulation development.
  • This formulation supports future clinical investigations of D-LSD for alcohol use disorder.