Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo

Figures & data

Figure 1 Ternary phase diagram. Light grey area represents the precipitate region, while the dark grey area represents the turbidity. Red area represents the milky region. Tween 80 = surfactant, Limonene = oil phase.

Figure 2 Morphology of different nano emulsion transdermal nanoparticle by TEM. (A) CTD-41. (B) CTD-12. (C) Schematic of the structural difference between CTD-41 and CTD-12. Arrows indicate the direction of change in formulation ratio.

Table 1 Numerical Results of 0–24 hr Skin Permeation for Free CBD, 6% Tween 80, CTD-41 and CTD-12

Group	Free CBD	6% Tween 80	CTD-41	CTD-12
Dose (mcg)	10,000
24 hr cumulative CBD content (mcg)	669.89 ± 8.92	747.94 ± 13.45	2189.76 ± 18.61	3521.45 ± 200.86
Membrane content (mcg)	73.07 ± 20.77	230.43 ± 8.31	1043.46 ± 29.59	1400.05 ± 45.14
Total CBD (mcg)	742.97 ± 29.69	978.37 ± 21.76	3233.22 ± 27.14	4921.50 ± 234.61
Release ratio (%)	7.43 ± 0.27	9.78 ± 0.19	32.33 ± 0.27	49.21 ± 2.35
Permeation ratio (%)	6.7 ± 0.09	7.48 ± 0.13	21.9 ± 0.19	35.21 ± 2.01
Flux0–24hr(mcg/hr∙cm^2)	15.8 ± 0.21	17.64 ± 0.31	51.66 ± 0.44	83.07 ± 4.74
AUC0-24hr(mcg∙hr)	10,234.09 ± 195.88	12,518.72 ± 160.11	24,886.41 ± 403.14	37,647.43 ± 1696.35
0–24 hr Relative FA (fold)	1	1.22 ± 0.02	2.43 ± 0.04	3.68 ± 0.17

Abbreviations: AUC_0-24hr, area under the curve-time curve from 0 to 24-hour time point, Flux_0-24hr, flux-time curve from 0 to 24-hour time point, FA, formulation bioavailability, CBD, Cannabidiol, CTD, Cannabidiol loaded transdermal nanocarriers.

Figure 3 (A) Cumulative CBD content (B) Flux (C) Permeation ratio of Free CBD, 6% Tween 80, CTD-41 and CTD-12 during 0–24 hr at skin permeation experiment.

Table 2 Numerical Results of 0–24 hr Skin Permeation for Free CBD Patch and PCTD-12

Group	Free CBD patch	PCTD-12
Dose (mg / patch)	8.47 ± 0.68	9.15 ± 1.02
24 hr cumulative CBD content (mcg)	147.25 ± 6.29	381.68 ± 33.5
Membrane content (mcg)	74.01 ± 1.77	668.85 ± 62.82
Total CBD (mcg)	221.26 ± 7.23	1050.53 ± 96.32
Release ratio (%)	2.62 ± 0.13	11.51 ± 0.28
Permeation ratio (%)	1.47 ± 0.06	3.82 ± 0.34
Flux0-24hr (mcg/hr∙cm^2)	3.47 ± 0.15	9.00 ± 0.79
AUC0-24hr (mcg∙hr)	1652.95 ± 76.36	4059.66 ± 297.71
0–24 hr Relative FA (fold) (Based on free CBD patch)	1	2.46 ± 0.18

Abbreviations: AUC_0-24hr, area under the curve-time curve from 0 to 24-hour time point, Flux_0-24hr, flux-time curve from 0 to 24-hour time point, FA, formulation bioavailability, CBD, Cannabidiol, PCTD, patch of cannabidiol loaded transdermal nanocarriers.

Figure 4 (A) Cumulative CBD content (B) Flux (C) Permeation ratio of Free CBD patch and PCTD-12 during 0–24 hr at skin permeation experiment.

Table 3 Numerical Results of 0–24 Hr Plasma Concentration Curve of Oral and PCTD-12

Group	Oral	PCTD-12
Dose (mg)	10	10.33 ± 1.67
C max (ng/mL)	85.77 ± 31.71	189.91 ± 3.80
T max (hr)	2 ± 0	3.33 ± 0.94
0–8hr cumulative (ng)	4338.77 ± 2412.88	17,336.41 ± 4256.51
0-24hr cumulative (ng)	4338.77 ± 2412.88	22,396.94 ± 5791.13
AUC 0–8 hr (ng/mL∙hr)	351.96 ± 173.94	1309.54 ± 70.05
AUC 0–24 hr (ng/mL∙hr)	351.96 ± 173.94	3332.90 ± 310.97
0–24 hr Relative BA (fold)	1	9.47 ± 0.88

Abbreviations: AUC_{0-t hr}, area under the curve-time curve from 0 to the time point, BA, bioavailability, PCTD, patch of cannabidiol loaded transdermal nanocarriers.

Figure 5 Plasma concentration curve of oral and PCTD-12 for 0–24 hours.