Engineering of a novel optimized platform for sublingual delivery with novel characterization tools: in vitro evaluation and in vivo pharmacokinetics study in human

Figures & data

Table 1. Composition of prepared MSP-PLCPs, percent yield, n-octanol/water partition coefficient (P), water solubility, n-octanol solubility, in vitro mucoadhesion time particles size, and PDI of MSP and MSP-PIPs.

Formula	Phospholipid type (PL)	Molar ratio (MSP:PL)	Yield (%) ± SD^a	P ± SD^a	Log P	Solubility in water (mg/ml) ±SD^a	Solubility in n-octanol (mg/ml) ±SD^a	In vitro flushing resistance time (s)±SD^a	Particle size (z-average nm)±SD^a	PDI ± SD^a
MSP	–	–	–	5.74 ± 0.08	0.76	1.34 ± 0.13	1.88 ± 0.39	7.00 ± 1.41	–	–
CP 1	SB 1	1:1	60.79 ± 5.78	19.46 ± 1.98	1.29	0.71 ± 0.02	2.56 ± 0.09	62.50 ± 10.60	372.70 ± 21.78	0.36 ± 0.029
CP 2	SB 1	1:2	76.87 ± 1.37	8.95 ± 0.13	0.95	0.72 ± 0.05	1.74 ± 0.21	150.00 ± 14.14	246.25 ± 6.86	0.38 ± 0.017
CP 3	SB 2	1:1	90.90 ± 2.27	62.33 ± 2.62	1.79	0.68 ± 0.08	3.94 ± 0.55	26.50 ± 4.94	356.95 ± 47.45	0.27 ± 0.019
CP 4	SB 2	1:2	96.06 ± 0.187	49.21 ± 9.94	1.69	0.32 ± 0.01	4.23 ± 0.14	99.00 ± 21.21	268.80 ± 1.56	0.40 ± 0.006

^a All readings are average of three replicates.

Table 2. Composition, disintegration time, wetting time, USP Q3, USP Q10, SSDT Q2, SSDT Q10, mucoadhesion time, and bioadhesion force of the prepared tablets.

Run	Polymer concentration (%)	Polymer type	Disintegration time (s)	Wetting time (s)	USP Q3	USP Q10 (% released)	SSDT Q2 (% released)	SSDT Q10 (% released)	SFRT (s)	SFRF (dyne/cm^2)
1	0	Na alginate	22	5	100	100	10.125	100	11	510.5
2	2	Na CMC	9	180	60.86	100	2.67	23.6	74	970.2
3	2	Na alginate	13	180	53.45	92.73	2.43	48.2	1836	1195.92
4	2	Na alginate	15	180	50.48	94.04	2.19	49.1	1860	1207.8
5	0	Na CMC	27	5	100	100	11.2	100	11	515.89
6	0	Na CMC	22	6	100	100	9.9	100	14	524.87
7	1	Na CMC	3	4	100	100	16.3279	66.1	61	863.28
8	2	Na CMC	11	180	63.8	98.6	2.31	26.1	88	926.64
9	1	Na CMC	5	7	100	100	17.0526	68.4	65	582.12
10	0	Na alginate	25	6	100	100	10.935	100	13	520.4

Figure 1. Schematic diagram for the new developed in vitro SSDT apparatus.

Figure 2. TEM micrographs of optimum MSP-PLCP (a and b) and TEM micrographs of the optimized tablet dispersion (c and d) in simulated saliva.

Figure 3. The effect of mucoadhesive polymer concentration on (a) disintegration time, (b) wetting time, (c) SSDT Q2 and (f) bioadhesion force. Combined effect of mucoadhesive polymer concentration and type on (d) SSDT Q10 and (e) mucoadhesion time. Desirability curve for optimization (g).

Table 3. Summary of the pharmacokinetic parameters of MSP following the sublingual administration of Fluxopride^® and the optimized test formulation.

Parameters	Fluxopride^®	T2
Cmax (ng/ml)	31.31 ± 9.65	42.38 ± 11.33
Tmax (median) (h)	1.125	1.125
MRT (median) (h)	4.70	5.66
AUC0–10 (ng h/ml)	103.25 ± 28.28	136.06 ± 41.43
AUC 0–∞ (ng h/ml)*	117.41 ± 26.70	165.99 ± 50.02
t1/2 (h)	3.34 ± 1.28	3.85 ± 0.79
k (h^−1)	0.22 ± 0.06	0.18 ± 0.03

* p < 0.05 (0.03).