Novel redispersible nanosuspensions stabilized by co-processed nanocrystalline cellulose–sodium carboxymethyl starch for enhancing dissolution and oral bioavailability of baicalin

Figures & data

Figure 1 Chemical structure of NCC (A) and SCS (B).

Abbreviations: NCC, nanocrystalline cellulose; SCS, sodium carboxymethyl starch.

Figure 2 The schematic image of BCA-NS stabilized by NCCS.

Abbreviations: BCA, baicalin; BCA-NS, BCA nanosuspension; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; SCS, sodium carboxymethyl starch; NCC, nanocrystalline cellulose; BCA-NP, BCA nanosuspension particle.

Table 1 Formula design of NCCS and BCA-NS/NCCS

Sample	Concentrations of dispersant (%, w/v)	Ratios of MCC and SCS in dispersant		BCA (%, w/v)
		MCC (%)	SCS (%)
S1-1	0.25	100	0	0
S1-2				1
S2-1		80	20	0
S2-2				1
S3-1		60	40	0
S3-2				1
S4-1		40	60	0
S4-2				1
S5-1		20	80	0
S5-2				1
S6-1	0.5	60	40	0
S6-2				1
S6-3		0	100	1
S7-1	1	60	40	0
S7-2				1
S8-1	2	60	40	0
S8-2				1

Abbreviations: BCA, baicalin; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; BCA-NS, BCA nanosuspension; MCC, microcrystalline cellulose; SCS, sodium carboxymethyl starch.

Figure 3 Particle sizes of NCCS (A) and BCA-NS/NCCS (B) before and after storage.

Note: D₁₀, D₅₀, and D₉₀ are the volumetric diameters where the 10%, 50%, and 90% of the population lies below each value, respectively.

Abbreviations: BCA, baicalin; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; BCA-NS, BCA nanosuspension.

Figure 4 The zeta potential of the freshly prepared NCCS and BCA-NS/NCCS that was co-processed by different ratios of MCC and SCS.

Abbreviations: BCA, baicalin; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; BCA-NS, BCA nanosuspension; MCC, microcrystalline cellulose; SCS, sodium carboxymethyl starch.

Figure 5 The shear thinning behavior of different NCCS (A) and BCA-NS/NCCS (B).

Abbreviations: BCA, baicalin; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; BCA-NS, BCA nanosuspension.

Figure 6 The viscoelastic property of the NCCS (S1-1–S8-1).

Abbreviation: NCCS, nanocrystalline cellulose–sodium carboxymethyl starch.

Figure 7 In vitro dissolution profiles of BCA from different BCA-NS/NCCSs (A) and BCA-NP/NCCSs (B).

Abbreviations: BCA, baicalin; BCA-NS, BCA nanosuspension; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; BCA-NP, BCA nanosuspension particle.

Table 2 RDI of BCA-NP/NCCS formulations with different ratios of NCCS

	S2-2	S3-2	S4-2	S5-2	S6-2	S7-2	S8-2
RDI	3.35±0.15	2.34±0.08	2.56±0.11	2.82±0.12	1.12±0.05	1.61±0.06	1.89±0.08

Abbreviations: BCA, baicalin; RDI, redispersibility index; BCA-NP, BCA nanosuspension particle; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch.

Figure 8 Particle size of NCCS (A), TEM morphology of NCCS (B), diagram of NCCS (C), particle size of BCA-NS/NCCS (D), TEM morphology of BCA-NS/NCCS (E), diagram of BCA-NS/NCCS (F), SEM of coarse BCA (G), SEM of BCA-NP/NCCS (20,000×, H), and SEM of BCA-NP/NCCS (50,000×, I).

Abbreviations: BCA, baicalin; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; TEM, transmitting electron microscopy; BCA-NS, BCA nanosuspension; SEM, scanning electron microscopy; BCA-NP, BCA nanosuspension particle.

Figure 9 DSC thermograms of raw MCC (A), SCS (B), the physical mixture of MCC and SCS (C), NCCS (D), coarse BCA (E), the physical mixture of NCCS and BCA (F), and BCA-NP/NCCS (G).

Abbreviations: DSC, differential scanning calorimetry; MCC, microcrystalline cellulose; SCS, sodium carboxymethyl starch; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; BCA, baicalin; BCA-NP, BCA nanosuspension particle.

Figure 10 XRD of MCC raw MCC (A), SCS (B), the physical mixture of MCC and SCS (C), NCCS (D), coarse BCA (E), the physical mixture of NCCS and BCA (F), and BCA-NP/NCCS (G).

Abbreviations: XRD, X-ray diffraction; MCC, microcrystalline cellulose; SCS, sodium carboxymethyl starch; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; BCA, baicalin; BCA-NP, BCA nanosuspension particle.

Figure 11 In vitro dissolution profiles of BCA from the spray-dried BCA-NP/NCCS after storage (A) and the schematic image on redispersion of BCA-NP/NCCS (B).

Abbreviations: BCA, baicalin; BCA-NP, BCA nanosuspension particle; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; SCS, sodium carboxymethyl starch.

Figure 12 Mean plasma concentration–time profiles in rats after oral administration of coarse BCA, BCA-NP/NCCS, and BCA-NS/NCCS at 100 mg/kg (n=6).

Abbreviations: BCA, baicalin; BCA-NP, BCA nanosuspension particle; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; BCA-NS, BCA nanosuspension.

Table 3 Main pharmacokinetic parameters of coarse BCA, BCA-NS/NCCS, and BCA-NP/NCCS after oral administration in rats (n=6, $\overline{x}+s$)

	Unit	BCA	BCA-NS/NCCS	BCA-NP/NCCS
MRT(0–∞)	Hours	7.92±0.24	7.58±0.51	6.87±1.45*
Tmax	Hours	7.62±0.89	6.85±1.77	7.24±1.05*
Cmax	ng·L^−1	630.83±86.48	1,198.46±113.81*	1,304.81±123.79*
t1/2	Hours	5.26±1.29	3.42±0.51	4.57±0.87
AUC(0–24)	µg/(L·h)	4,354.61±451.28	8,036.42±510.16**	8,773.38±718.18**

Notes:

* P<0.05 and

** P<0.01 vs control group. C_max, mean peak concentration.

Abbreviations: BCA, baicalin; BCA-NS, BCA nanosuspension; NCCS, nanocrystalline cellulose–sodium carboxymethyl starch; BCA-NP, BCA nanosuspension particle; MRT_(0–∞), mean residence time; T_max, peak time; t_1/2, half-life time; AUC_(0–24), area under the curve.