Towards Enhanced Solubility of Cannabidiol: Preparation and Evaluation of Cannabidiol Solid Dispersions Using Vacuum Compression Molding

The present study aims to develop and characterize cannabidiol (CBD) solid dispersions using Vacuum Compression Molding (VCM) to enhance the drug solubility and release profile. Solid dispersions of CBD and polymers were processed using VCM at 130 °C for 4 min after a prior physical mixing. Five percent w/w of CBD was used with 5% w/w of poloxamer 188 and 90% w/w of polymeric carrier (Polyethylene Oxide, PEO-N80 or Hydroxypropyl cellulose, HPCEF). Discs were collected and milled to obtain formulations (F1V, F2V). The degradation temperature of CBD was determined using Thermogravimetric Analysis (TGA). The formulations were further characterized using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier-Transform Infrared Spectroscopy (FTIR). In vitro dissolution testing of pure CBD and formulations was evaluated using USP apparatus II. TGA showed that CBD degradation occurs after 200 °C. FTIR spectra of formulations indicate potential interactions between the drug and polymers. DSC thermograms of F1V showed a thermal peak at 65 °C that could correspond to PEO-N80. F2V did not show any of the thermal event peaks, which suggests the conversion of the drug to the amorphous state. Images from the SEM showed irregular surfaces for both formulations. The release profile showed an increase in the CBD dissolution rate by 4.75 folds for F1V and 3.63 folds for F2V in four hours. In this study, solid dispersions of CBD formulations were successfully achieved. The VCM technology has proven to be successful in formulating solid dispersions of CBD for early-stage drug development.

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Materials

Cannabidiol (CBD) was kindly gifted by ElSohly Laboratories, Inc. (Oxford, MS, USA). Hydroxypropyl cellulose (Klucel™ EF) was gifted from Ashland (Wilmington, DE, USA). Polyethylene Oxide (Polyox™ N80) was gifted from Colorcon (Lower Salford Township, PA, USA). Poloxamer 188 and HPLC grade solvents were purchased from Fisher Scientific (Fair Lawn, NJ, USA).

Methods

Preparation of CBD Solid Dispersion by VCM

Solid dispersions of CBD and polymers (PEO-N80 and HPC-EF) were performed using VCM (MeltPrep, East Setauket, NY, USA). For the two formulations, 5% w/w of CBD was mixed with 5% w/w of Poloxamer 188 and 90% w/w polymer using a mortar and pestle. 300 mg of physical mixture was added to the VCM chamber. The physical mixture was heated in a hot plate at 130 °C for 4 min and then cooled in a cooling plate using compressed air. Discs of 20 mm diameter were collected and milled using a blade coffee grinder with dry ice to obtain pellets suitable to fill capsules.

Cherif, A., Deshmukh, J., Sanil, K. et al. Towards Enhanced Solubility of Cannabidiol: Preparation and Evaluation of Cannabidiol Solid Dispersions Using Vacuum Compression Molding. AAPS PharmSciTech 26, 83 (2025). https://doi.org/10.1208/s12249-025-03078-8