Impact of Formulation Variables on the Quality Attributes of Psilocybin-Loaded Oral Thin Films for Early-Phase Development
Vorawut Wongumpornpinit, K Ingkaninan, Prapapan Temkitthawon, Neti Waranuch, Rhannanda Copetti Pivetta, Jieyu Zuo, Gabriel Lima Barros de Araújo, Nádia Bou-Charcra, Vijay Somayaji, Raimar Loebenberg
Journal of Drug Delivery Science and Technology March 1, 2026 DOI: 10.1016/j.jddst.2026.108228 via OpenAlex
Summary
AI-generated from the abstractPsilocybin, an investigational compound for neuropsychiatric disorders, was successfully incorporated into oral thin film (OTF) formulations using a solvent casting process. The films disintegrated and dissolved within 180 seconds, with drug loading ranging from 6.73% to 24.07% and recovery between 89.78% and 99.56%. The maximum amorphous psilocybin loading without detectable crystallinity was 11.75%. Stability studies over three months at 25°C/60% RH and 40°C/75% RH showed no significant changes in film appearance or drug content. The OTF platform enables flexible dose adjustment and broad dose exploration within a single stability program, supporting efficient formulation development for early-phase clinical trials.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Intervention | Psilocybin-loaded oral thin film |
| Duration | Three months |
| Topics | Psilocybin |
| Keywords | Dissolution Thin film Crystallinity Amorphous solid |
| Key finding | Psilocybin-loaded oral thin films with acceptable short-term physical and chemical stability were successfully developed, supporting their suitability for early-phase pharmaceutical development. |
Abstract
Psilocybin is an emerging investigational compound with therapeutic potential in neuropsychiatric disorders, creating a need for flexible and scalable dosage forms suitable for early clinical development. This study aimed to develop and evaluate psilocybin-loaded oral thin film (OTF) formulations as a dose-proportional platform for early-phase clinical use. OTFs were prepared using a solvent casting process and characterized with respect to physicochemical properties, drug loading, content uniformity, disintegration, dissolution behavior, and short-term stability. Psilocybin was fully solubilized in the aqueous phase and successfully incorporated into the polymeric film matrix. All formulations disintegrated and dissolved within 180 s. Drug loading ranged from 6.73% to 24.07%, with recovery between 89.78% and 99.56%. The maximum amorphous psilocybin loading without detectable crystallinity was 11.75%. Stability studies conducted at 25 ± 2 °C / 60 ± 5% RH and 40 ± 2 °C / 75 ± 5% RH over three months demonstrated no significant changes in film appearance or drug content. A psilocybin-loaded oral thin film formulation with acceptable short-term physical and chemical stability was successfully developed, supporting its suitability for early-phase pharmaceutical development. Owing to their inherent dose proportionality based on film size, OTFs enable flexible dose adjustment and broad dose exploration within a single bracketed stability program, supporting efficient formulation development for early-phase clinical trials.