# Combined extraction and spray-freeze-drying of Cannabis sativa Flos provides stable lyophilizate particles of cannabinoids

## TL;DR

This study shows that a new drying method can stabilize and improve the delivery of cannabis extracts containing important cannabinoids.

## Contribution

The novel use of non-aqueous spray-freeze-drying to stabilize and enhance the dissolution of Cannabis sativa full extracts is introduced.

## Key findings

- Spray-freeze-dried particles with PVP and HPMC-AS excipients significantly improved cannabinoid stability at elevated temperatures.
- PVP, PEG 6000, and HPMC-AS SFD particles enhanced the dissolution rate of THC and CBD compared to raw extract.
- Non-aqueous spray-freeze-drying is a promising method for formulating heat-sensitive cannabis extracts into stable solid-state products.

## Abstract

The objective of this study was to explore non-aqueous spray-freeze-drying (SFD) as a formulation strategy to stabilize and improve the dissolution of Cannabis sativa full extracts. The medicinal use of Cannabis sativa has strongly intensified over the last decade. Here, Cannabis flos full extracts prepared by tert-butanolic solutions with 25% solid content were directly processed via spray-freeze-drying (SFD) with different excipients to increase the storage stability of the 4 main cannabinoids: tetrahydrocannabinol (THC), cannabidiol (CBD) and their corresponding acid precursors (THCA and CBDA). A variety of pharmaceutical excipients, namely polyvinyl pyrrolidone (PVP), HPMC-AS, PEG 6000, cetyl alcohol, or shellac were investigated for their sprayability and ability to form spray-freeze-dried particles (with a constant 25% cannabis resin content). SFD formulations varied in median diameter between 230 and 400 μm, depending on the respective excipient. The long term-stability tests revealed that, in the pure dried extract, the four cannabinoids were almost entirely degraded after 6 months at 40 °C, while PVP and HPMC-AS SFD-particles achieved a significant improvement in chemical stability of the tracked cannabinoids at 25 °C and 40 °C. Preliminary dissolution tests revealed that particles made from PVP, PEG 6000, and HPMC-AS enhanced the dissolution rate of THC and CBD, reaching higher concentrations than the raw extract before plateauing. It was demonstrated that non-aqueous spray-freeze-drying can be an advantageous process to formulate heat-sensitive, water-insoluble extracts into solid-state products with improved stability, offering a promising platform for future oromucosal and potentially nasal product development, pending further deposition and performance studies.

The online version contains supplementary material available at 10.1186/s42238-025-00381-w.