Preparation of multiple-unit floating-bioadhesive cooperative minitablets for improving the oral bioavailability of famotidine in rats

Figures & data

Table 1. The composition of the investigated different formulations of famotidine minitablets.

Composition (mg/capsule)
	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10
FMTD	20	20	20	20	20	20	20	20	20	20
HPMC K4M	22.5	67.5	112.5	157.5	112.5	112.5	112.5	112.5	112.5	135
Carbopol 971P	22.5	22.5	22.5	22.5	22.5	22.5	22.5	11.25	45	0
NaHCO3	11.25	11.25	11.25	11.25	4.5	22.5	45	11.25	11.25	22.5
MCC	144.25	99.25	54.25	9.25	61	43	20.5	65.5	31.75	43
Aerosil	2.25	2.25	2.25	2.25	2.25	2.25	2.25	2.25	2.25	2.25
Magnesium stearate	2.25	2.25	2.25	2.25	2.25	2.25	2.25	2.25	2.25	2.25

Figure 1. Effect of different kinds of hydrogel matrix material (HPMC K4M and Carbopol 971 P) on swelling behavior showing swelling indices (%) of famotidine minitablets under the conditions of 0.1 M HCl and 37 °C (apparatus II, 50 rpm) (mean ± SD, n = 6).

Table 2. The influence of different concentrations of HPMC K4M on the floating lag time and duration of minitablets.

HPMC K4M	F1	F2	F3	F4
Floating lag time (min)	10	5	3	3
Total floating time (h)	3	>8	>8	>8

Table 3. The influence of different concentrations of NaHCO₃ on the floating lag time and duration of minitablets.

NaHCO3	F5	F3	F6	F7
Floating lag time (min)	8	3	<1	<1
Total floating time (h)	2	>8	>8	>8

Figure 2. Photographs taken during in vitro buoyancy study of F6 in 150 mL 0.1 M HCl at different time intervals (10 s, 30 s, 60 s, 1 h, 4 h, 8 h).

Figure 3. Effect of different concentrations of HPMC K4M (10.00%, w/w; 30.00%, w/w; 50.00%, w/w; 70.00%, w/w) on in vitro release of famotidine minitablets under the conditions of 0.1 M HCl and 37 °C (apparatus II, 50 rpm) (mean ± SD, n = 6).

Figure 4. Effect of different kinds of matrix material (HPMC K4M and EC) on in vitro release of famotidine minitablets under the conditions of 0.1 M HCl and 37 °C (apparatus II, 50 rpm) (mean ± SD, n = 6).

Figure 5. Effect of different concentrations of NaHCO₃ (2%, w/w; 5%, w/w; 10%, w/w; 20%, w/w) on in vitro release of famotidine minitablets under the conditions of 0.1 M HCl and 37 °C (apparatus II, 50 rpm) (mean ± SD, n = 6).

Figure 6. Effect of different diameters (3 mm, 5 mm, 7 mm, 9 mm) on in vitro release of famotidine tablets under the conditions of 0.1 M HCl and 37 °C (apparatus II, 50 rpm) (mean ± SD, n = 6).

Figure 7. Photographs taken of different diameters (3 mm, 5 mm, 7 mm, 9 mm) of famotidine tablets.

Figure 8. Effect of different dissolution mediums (0.1 M HCl, distilled water, pH 6.8 PBS, pH 7.4 PBS) on in vitro release of famotidine minitablets (apparatus II, 50 rpm) (mean ± SD, n = 6).

Table 4. R-square of the optimized formulation fitted to zero-order, first-order and Higuchi equations.

Model	Fitting equation	R-square
Zero-order model	Mt/M∞ = kt	0.782
First-order model	In(1 − Mt/M∞) = − kt	0.967
Higuchi model	Mt/M∞ = kt^1/2	0.945

Figure 9. Plasma concentration-time profiles of famotidine in rats given famotidine minitablets and reference tablets (XinFaDing®) (mean ± SD, n = 6).

Table 5. The main pharmacokinetic parameters obtained following oral administration of XinFaDing® and the minitablets containing famotidine to rats.

Parameters	Unit	Minitablets	Market tablets
AUC0–t	ng/mL h	3880.96 ± 447.42*	2505.40 ± 275.61
AUC0–∞	ng/mL h	4096.49 ± 520.06*	2514.06 ± 279.59
t1/2	h	2.23 ± 0.69*	1.14 ± 0.28
Cmax	ng/mL	717.30 ± 68.44	921.92 ± 111.95
Tmax	h	3*	1.5

*p < 0.05 versus control group; Tukey test.