Loratadine bioavailability via buccal transferosomal gel: formulation, statistical optimization, in vitro/in vivo characterization, and pharmacokinetics in human volunteers

Figures & data

Figure 1. Constrained simplex-centroid design for optimization of a ternary surfactant mixture (upper panel), and ternary response surface plots showing the effect of mixture composition on measured responses (lower panel).

Table 1. ANOVA of responses measured according to the Plackett–Burman design.

Factors	DF	SS	MS	F	p value	Effect
Entrapment efficiency
Lipophilic surfactant	1	5434	5434	64.9	<0.001	−15.0
Ratio of lipid and edge activator to surfactant	1	430	430	5.13	0.036	−4.23
Sonication time	1	473	473	5.64	0.030	−4.44
Edge activator	1	91	91	1.09	0.312	−1.95
Ratio of lipid to edge activator	1	12	12	0.145	0.708	−0.71
Hydrophilic surfactant	1	1971	1971	23.5	<0.001	9.06
Residual	17	1424	84
Particle size
Lipophilic surfactant	1	135 300	135 300	16.3	0.001	−75.1
Ratio of lipid and edge activator to surfactant	1	470	470	0.057	0.814	−4.42
Sonication time	1	10 559	10 559	1.28	0.274	21.0
Edge activator	1	12 974	12 974	1.57	0.228	−23.3
Ratio of lipid to edge activator	1	117	117	0.014	0.907	−2.21
Hydrophilic surfactant	1	88 161	88 161	10.6	0.005	−60.6
Residual	17	140 813	8283

DF: degrees of freedom; SS: sums of squared error; MS: mean squared error (MS = SS/DF); F: Fisher’s ratio (F = MS_Regression/MS_Residual).

Figure 2. Transmission electron micrographs of optimized LTD-TRS formulation.

Figure 3. LTD in vitro release (A) and permeation across chicken buccal mucosa (B) from the transferosomal gel relative to the control gel. Plot (C) is correlation of percentage LTD permeated and released from the transferosomal and control gels.

Figure 4. Average (+SD) Plasma LTD cementations following administration of 10 mg LTD in transferosomal buccal gel and marketed Claritin® tablet in three healthy human volunteers (A), and Level A IVIVC plot for LTD in the transferosomal buccal gel (B). Plasma concentrations of both formulations at each time point in plot (A) were not significantly different on ANOVA test (p > 0.05).

Table 2. Pharmacokinetic parameters of LTD after buccal administration of the transferosomal gel and the marketed tablet (Claritin®) in 10 mg doses to three healthy human volunteers.

Parameter	LTD-TRS buccal gel	Claritin® oral tablets	ANOVA p value
Cmax (ng/mL)	2.13 ± 0.25 (11.5)	5.90 ± 2.83 (48)	>0.05
Tmax (h)	2.50 ± 0.71 (28.3)	2.50 ± 0.71 (28.3)	>0.05
AUC0–24 (ng h/mL)	12.1 ± 1.11 (9.22)	18.8 ± 17.9 (94.8)	>0.05
AUC0–∞ (ng h/mL)	12.4 ± 0.679 (5.48)	19.1 ± 18.1 (95.3)	>0.05
MRT (h)	4.40 ± 0.52 (11.8)	3.34 ± 0.577 (17.3)	>0.05
t0.5 (h)	3.94 ± 3.86 (97.8)	2.77 ± 1.59 (57.4)	>0.05

Values are mean ± SD (%CV). %CV is percentage coefficient of variation (calculated as SD/mean × 100).