Increasing the oral bioavailability of poorly water-soluble carbamazepine using immediate-release pellets supported on SBA-15 mesoporous silica

Figures & data

Figure 1 Scanning electron microscopic images of (A) crystalline carbamazepine, (B) SBA-15, (C) physical mixture of 20% carbamazepine and SBA-15, (D) 20% SBA-15-CBZ, (E) SBA-15-CBZ pellets (15×), and (F) SBA-15-CBZ pellet (95×).

Abbreviations: CBZ, carbamazepine; SBA-15, Santa Barbara Amorphous-15 mesoporous silica.

Figure 2 Transmission electron microscopic images of SBA-15 (A) at parallel orientation and (B) at vertical orientation.

Abbreviation: SBA-15, Santa Barbara Amorphous-15 mesoporous silica.

Table 1 Structural parameters of SBA-15 before and after loading CBZ

Sample	BET surface area (m^2/g)	Pore volume (cm^3/g)	Pore size (nm)
SBA-15	648	0.62	6.5
20% SBA-15-CBZ	325	0.39	5.6

Abbreviations: BET, Brunauer–Emmett–Teller; CBZ, carbamazepine; SBA, Santa Barbara Amorphous-15 mesoporous silica.

Figure 3 Small-angle x-ray diffraction patterns of (A) SBA-15 and (B) 20% SBA-15-CBZ.

Abbreviations: CBZ, carbamazepine; SBA-15, Santa Barbara Amorphous-15 mesoporous silica.

Figure 4 Nitrogen adsorption/desorption isotherms of (A) SBA-15 and (B) 20% SBA-15-CBZ. Pore size distributions of (A) SBA-15 and (B) 20% SBA-15-CBZ in the insert.

Abbreviations: CBZ, carbamazepine; SBA-15, Santa Barbara Amorphous-15 mesoporous silica.

Figure 5 Wide-angle x-ray diffraction patterns of (A) crystalline carbamazepine, (B) physical mixture of 20% carbamazepine and SBA-15, (C) 10% SBA-15-CBZ, (D) 20% SBA-15-CBZ, and (E) 30% SBA-15-CBZ.

Abbreviations: CBZ, carbamazepine; SBA-15, Santa Barbara Amorphous-15 mesoporous silica.

Figure 6 Thermal behavior of (A) pure carbamazepine, (B) physical mixture of 20% carbamazepine and SBA-15, (C) 10% SBA-15-CBZ, (D) 20% SBA-15-CBZ, and (E) 30% SBA-15-CBZ.

Abbreviations: CBZ, carbamazepine; SBA-15, Santa Barbara Amorphous-15 mesoporous silica.

Table 2 Powder properties of 20% SBA-15-CBZ powder and pellets (n = 3)

Sample	Bulk density (g/cm^3)	Tapped density (g/cm^3)	Angle of repose (degrees)
SBA-15	0.223 ± 0.02	0.321 ± 0.02	48.9 ± 0.58
SBA-15-CBZ powder	0.210 ± 0.01	0.301 ± 0.02	49.8 ± 1.16
SBA-15-CBZ + excipients	0.325 ± 0.01	0.494 ± 0.02	36.9 ± 1.25
SBA-15-CBZ pellets	0.718 ± 0.03	0.758 ± 0.01	23.8 ± 0.8

Abbreviations: CBZ, carbamazepine; SBA-15, Santa Barbara Amorphous-15 mesoporous silica.

Figure 7 Release profiles of carbamazepine from crystalline carbamazepine, a physical mixture of 20% CBZ and SBA-15, and the corresponding SBA-15-CBZ powder and SBA-15-CBZ pellets in deionized water. Each datum point represents the mean ± standard deviation of three determinations.

Abbreviations: CBZ, carbamazepine; SBA-15, Santa Barbara Amorphous-15 mesoporous silica.

Table 3 Pharmacokinetic parameters (mean±SD) of carbamazepine following oral administration of a single 100 mg dose of commercial tablets and prepared SBA-15-CBZ pellets (n = 6)

PK parameter	Commercial tablet	SBA-15-CBZ pellet	P value
Cmax (ng/mL)	528.83 ± 106.85	803.70 ± 296.78	0.059
Tmax (min)	65.00 ± 15.49	65.00 ± 12.25	0.865
Ke (min^−1)	0.01 ± 0.00	0.01 ± 0.00	0.317
t1/2 (min)	59.24 ± 39.19	57.37 ± 24.21	0.200
AUC(0→∞) (ng · h/mL)	72580.30 ± 25283.90	113709.91 ± 17150.92	0.007

Abbreviations: AUC_(0→∞), area under the plasma concentration-time curve calculated by the linear trapezoidal rule from time 0 to infinity; CBZ, carbamazepine; PK, pharmacokinetic; SBA-15, Santa Barbara Amorphous-15 mesoporous silica; SD, standard deviation; t_1/2, elimination half-life; C_max, peak plasma concentration; T_max, time to reach peak plasma concentration; K_e, slope of the logarithm concentration-time plot estimated from the elimination segment.

Figure 8 Mean carbamazepine plasma profiles following a single dose, crossover bioavailability study comparing SBA-15-CBZ pellets with commercial carbamazepine tablets (n = 6).

Abbreviations: CBZ, carbamazepine; SBA-15, Santa Barbara Amorphous-15 mesoporous silica.