(M1030-03-20) CBD Solid Dispersion by Spray Drying

Purpose: In recent years, the therapeutic benefits of cannabidiol (CBD) have been recognized in both nutraceutical and pharmaceutical markets. When formulating CBD, there are several aspects to be taken into consideration: low melting point, water insolubility, taste masking and poor bioavailability. Developing a CBD solid dispersion by spray drying, we aimed to broaden CBD application (currently mainly ethanol extracts and topical creams) towards solid dosage forms to increase patient compliance.

Methods: An emulsion of oil phase of 15% 10/5 ratio of CBD Distillate / MCT (medium chain triglyceride, LABRAFAC LIPOPHILE WL 1349, Gattefosse) was initially high speed homogenized with KLEPTOSE^® Linecaps pea maltodextrin (Roquette) as a carrier and CLEARGUM^® CO 03 (octenyl succinate starch ,Roquette) as surfactant at 10000 rpm (IKA T 50 Basic ULTRA-TURRAX®) followed by high pressure homogenization (High Pressure homogenizer GEA Panther NS3006L) at 10,000 psi for 5 cycles and 13,000 psi for 6th cycle, in iced water bath (figure 1). Emulsion spray drying (GEA MOBILE MINOR®) was performed using a two-fluid nozzle and 80 kg/h Nitrogen as drying gas. Process temperature was varied at a high and low set of conditions: Tin=165 and Tin=135. CBD potency was evaluated by High Performance Liquid Chromatography (HPLC) equipped with a diode array detector at a wavelength of 235 nm. Particle size distribution (Malvern Mastersizer 3000), moisture content, powder characterization was evaluated. Thermal analysis of spray dried CBD solid dispersion and individual components of formulation were performed using Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA).

Results: Processibility of the formulation was feasible under mentioned conditions and created a stable emulsion at 113 mg CBD/ml potency. All formulations were adjustable to both low and high temperature conditions, while maintaining emulsion temperature at approximately 50°C during the drying process. Atomization stability was improved using a 2.0 mm nozzle insert compared to a 1.0 mm insert used previously. CBD potency in the resulting solid dispersions between 100 mg/g.-103mg/g. The particle size (d50) for low and high spray drying conditions samples were 44.3 µm and 43.4 µm, and the residual moisture was 4.9% and 5.5% respectively. Individual components CBD, CLEARGUM^® CO 03, KLEPTOSE^® Linecaps showed endotherm peak at 62.55 °C, 95.42 °C, and 103.74°C respectively. Spray dried CBD solid dispersion samples exhibited endotherm peak close to 90 °C for all samples (figure 2). Degradation started from 200 °C as displayed by TGA thermograms for all individual formulation components and CBD spray dried emulsions.

Conclusion: (1) CBD solid dispersion by spray drying offers a stable alternative to existing marketed presentations of CBD which are mainly in ethanol extracts and topical creams with short shelf life. (2) KLEPTOSE^® Linecaps maltodextrin and CLEARGUM® starch showed excellent incorporation efficiency of CBD by increasing its thermal stability (as a solid dispersion) by elevated melting point from 62.55 °C to 94.48 °C. (3) CBD as a solid dispersion increases patients’ compliance by formulating it as a tablet, sachets, film strips, etc.

Figure 1: CBD solid powder solubilization in MCT and incorporation into the emulsion for spray drying to get CBD solid dispersion

Figure 2: DSC thermogram overlay of (a) CBD distillate, (b) CLEARGUM® CO 03, (c) KLEPTOSE® Linecaps, (d) CBD SD 10/05 LO Conditions JAN, (e) CBD SD 10/05 HI Conditions JAN, (f) R2-3 GEA MM SD APRIL, (g) R1-4 GEA MM SD APRIL, (h) R1-3 GEA MM SD APRIL