Exploring the interconnected properties of cannabidiol suspensions and orodispersible films

Abstract

In this study, orodispersible films (ODFs) were developed as fast-releasing formulations for pediatric patients suffering from Lennox-Gastaut or Dravet syndrome, with cannabidiol (CBD) selected as the active pharmaceutical ingredient (API). The properties of the ODFs were evaluated both before and after casting, with a focus on establishing a correlation between the properties of colloidal dispersion/suspension and ODFs to enhance understanding of the manufacturing process. Two blank colloidal dispersions were characterized for spreadability, viscosity, tangential stress, and pH, and their properties were correlated with those of blank ODFs, including mass uniformity, thickness, folding endurance, thickness-normalized crushing strength, disintegration time (evaluated through two different methods) and adhesivity. The strength and direction of the correlation were established via the Pearson coefficient. The same statistical approach was applied to assess correlation between CBD suspension (DCBD1, DCBD2) properties and CBD-ODF parameters. For the suspensions, particle size evaluation was also considered. Although few statistically significant positive or negative correlations were observed, a notable finding of this study was the dissolution behavior of CBD-ODF2, where nearly 100% of the API was released at 30 min, which is consistent with the disintegration behavior evaluated through the pharmacopeial method. Notably, CBD is classified as a Biopharmaceutical Classification System (BCS) Class II compound.

Keywords: Colloidal dispersions; Correlation coefficients; Dissolution behavior; Polymeric films.

Fig. 1

The spectrograms and characteristic bands for the API, excipients, and binary mixtures: CBD: CA (a), CBD: HPMCE3 (b), CBD: SUCR (c), and CBD: PVA (d).

Fig. 2

(a) Dunn’s multiple comparisons test results for the pH of the prepared colloidal dispersions. (b) Dunn’s T3 multiple comparisons test results for the conductivity of the prepared colloidal dispersions. ns (p > 0.05), ns—not significant, * (p < 0.05); ** (p < 0.01); *** (p < 0.001); **** (p < 0.0001).

Fig. 3

The particle size distributions and average sizes of the DCBD1 (a), DCBD2 (b).

Fig. 4

(a) Dunnett’s T3 multiple comparisons test results for the uniformity of mass. ns (p > 0.05), ns—not significant, * (p < 0.05); ** (p < 0.01); *** (p < 0.001); **** (p < 0.0001). (b) Dunn’s multiple comparisons test results for the thickness measurement. ns (p > 0.05), ns—not significant, * (p < 0.05); ** (p < 0.01); *** (p < 0.001); **** (p < 0.0001). (c) Dunnett’s T3 multiple comparisons test results for the folding endurance. ns (p > 0.05), ns—not significant, * (p < 0.05); ** (p < 0.01); *** (p < 0.001); **** (p < 0.0001). (d) Dunnett’s T3 multiple comparisons test results for thickness-normalized tensile strength. ns (p > 0.05), ns—not significant, * (p < 0.05); ** (p < 0.01); *** (p < 0.001); **** (p < 0.0001). (e) Dunn’s multiple comparisons test results for adhesivity. ns (p > 0.05), ns—not significant, * (p < 0.05); ** (p < 0.01); *** (p < 0.001); **** (p < 0.0001). (f) Dunnett’s T3 multiple comparisons test results for pH. ns (p > 0.05), ns—not significant, * (p < 0.05); ** (p < 0.01); *** (p < 0.001); **** (p < 0.0001). (g) Dunn’s multiple comparisons test results for the disintegration time through the pharmacopeial method. ns (p > 0.05), ns—not significant, * (p < 0.05); ** (p < 0.01); *** (p < 0.001); **** (p < 0.0001). (h) Dunn’s multiple comparisons test results for the disintegration time through the slide frame method. ns (p > 0.05), ns—not significant, * (p < 0.05); ** (p < 0.01); *** (p < 0.001); **** (p < 0.0001). (i) UV‒Vis spectrophotometry method linearity (1) and the statistical evaluation between the two CBD-ODFs via the t-test with Welch’s correction (2). ns (p > 0.05), ns—not significant, * (p < 0.05); ** (p < 0.01); *** (p < 0.001); **** (p < 0.0001).

Fig. 5

Dissolution test results for the CBD-ODF formulations.

Fig. 6

Preparation steps for CBD suspensions and ODFs.