Development of bioadhesive buccal tablets for felodipine and pioglitazone in combined dosage form: In vitro, ex vivo, and in vivo characterization

Figures & data

Table 1.  Composition of FDP-PIO bioadhesive buccal tablets.

Ingredient	Formulation (mg per tablet)
	PF1	PF2	PF3	PF4	PF5	PF6
Pioglitazone	15	15	15	15	15	15
Felodipine	5	5	5	5	5	5
HPβCD			22			22
Carbopol 971P	10	5	5	2.5	5	5
Sod.CMC	50	35	35	37.5
HPMC K4M					20	20
Pearlitol	28	48	26	48	63	41
SSF	2	2	2	2	2	2

Figure 1.  Ex vivo permeation of (a) FDP and (b) PIO solution through porcine buccal mucosa (mean ± SD, n = 3).

Table 2.  Physicomechanical and bioadhesive properties of buccal tablets.

Batch code	SI	Erosion	IR (min)	Surface pH	PF (N)	WA (mJ)
PF1	187 ± 12	4.54 ± 0.62	265 ± 35	5.68 ± 0.2	1.80 ± 0.04	0.53 ± 0.03
PF2	194 ± 13	16.5 ± 2.05	235 ± 40	5.92 ± 0.1	1.62 ± 0.03	0.34 ± 0.02
PF3	278 ± 11	17.5 ± 2.15	280 ± 30	6.42 ± 0.3	2.86 ± 0.08	0.64 ± 0.03
PF4	116 ± 09	15.4 ± 2.68	180 ± 25	6.18 ± 0.1	1.65 ± 0.07	0.48 ± 0.02
PF5	163 ± 08	18.6 ± 1.85	234 ± 28	5.96 ± 0.3	2.08 ± 0.06	0.42 ± 0.05
PF6	196 ± 09	10.8 ± 1.86	292 ± 36	6.50 ± 0.2	3.12 ± 0.09	0.72 ± 0.03

S.I., Swelling Index; IR, In vivo Residence Time; PF, Peak Detachment Force; WA, Work of Adhesion.

Figure 2.  Cumulative percentage of (a) FDP and (b) PIO released from bioadhesive buccal tablets.

Table 3.  FDP and PIO estimated values of release exponent (n) and correlation coefficients (r²), in combined dosage form for all of the formulations.

Formulation	n value	r^2 (Zero-order)	r^2 (First order)	r^2 (Higuchi)	r^2 (Peppas)
FDP
PF1	0.725	0.984	0.780	0.878	0.442
PF2	0.880	0.932	0.722	0.882	0.556
PF3	0.684	0.900	0.763	0.946	0.602
PF4	0.822	0.740	0.647	0.838	0.604
PF5	0.674	0.955	0.813	0.952	0.566
PF6	0.651	0.889	0.788	0.937	0.596
PIO
PF1	0.806	0.991	0.873	0.879	0.445
PF2	0.877	0.951	0.798	0.914	0.569
PF3	0.721	0.926	0.794	0.943	0.592
PF4	0.674	0.785	0.669	0.899	0.609
PF5	0.668	0.967	0.844	0.946	0.524
PF6	0.600	0.885	0.734	0.949	0.608

Figure 3.  Mean serum profiles of (a) FDP and (b) PIO in pigs, after administration of oral solution and buccal tablet, values represented are mean ± SD (n = 6).

Table 4.  Pharmacokinetic parameters of FDP and PIO in pigs after administration of oral suspension and bioadhesive buccal tablet, values represented are mean ± SD (n = 6).

Formulation	Cmax (ng/mL)	Tmax (h)	AUC0–t (ng^−1h^−1mL^−1)	AUC0–∞ (ng^−1h^−1mL^−1)
Felodipine
Oral suspension	61.3	2.7	212.0	212.2
Buccal tablet	62.6	6.7	435.9	440.6
Pioglitazone
Oral suspension	358.9	2.4	1351.7	1358.7
Buccal tablet	404.6	6.4	2884.2	2908.9

Table 5.  Stability study of the optimized formulation (PF6) for 3 months.

Time	Drug content (mg)		% drug released (Q6)		Cumulative % drug permeated (Q6)
	FDP	PIO	FDP	PIO	FDP	PIO
Initial	4.95 ± 0.06	14.87 ± 0.24	98.9 ± 1.68	99.6 ± 0.98	66.1 ± 2.68	64.6 ± 2.34
1 Month	4.86 ± 0.08	14.64 ± 0.16	96.4 ± 3.12	96.7 ± 2.86	68.5 ± 3.28	63.5 ± 1.89
2 Months	4.79 ± 0.11	14.48 ± 0.32	97.6 ± 2.08	98.1 ± 1.84	65.3 ± 1.96	62.4 ± 3.14
3 Months	4.91 ± 0.07	14.52 ± 0.28	98.2 ± 1.34	97.4 ± 2.42	63.2 ± 3.88	61.9 ± 3.46
6 Months	4.68 ± 0.12	14.41 ± 0.36	97.3 ± 2.14	96.9 ± 2.36	62.5 ± 3.46	60.8 ± 3.32

Figure 4.  Ex vivo–n vivo correlation of cumulative amount of (a) FDP and (b) PIO permeated ex vivo vs AUC.