Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation

Figures & data

Table 1 Particle size of carvedilol microsuspensions and nanosuspensions (mean ± SD, n=3)

Preparation	Size distribution (nm)			Span
	D10	D50	D90
Microsuspensions
Before lyophilization	816±217	4,895±189	9,987±536	1.87
After lyophilization	798±239	4,954±227	10,871±412	2.03
Nanosuspensions
Before lyophilization	177±7	212±12	255±15	0.37
After lyophilization	172±13	224±9	271±6	0.44

Note: D₁₀, D₅₀, and D₉₀ represent represent 10%, 50%, and 90%, respectively, of the cumulative particle size distribution.

Figure 1 SEM micrographs.

Notes: SEM micrographs of (A) carvedilol coarse powder, (B) microsuspensions, and (C) nanosuspensions.

Abbreviations: EHT, extra high tension; SEM, scanning electron microscopy; WD, working distance.

Figure 2 DSC profiles.

Notes: DSC profiles of freeze-dried nanosuspension powder (A), freeze-dried microsuspension powder (B), physical mixture (C), SDS powder (D), VES powder (E), and coarse carvedilol powder (F).

Abbreviations: DSC, differential scanning calorimetry; SDS, sodium dodecyl sulfate; VES, α-tocopherol succinate.

Figure 3 PXRD patterns.

Notes: PXRD patterns of freeze-dried nanosuspension powder (A), freeze-dried microsuspension powder (B), physical mixture (C), SDS powder (D), VES powder (E), and coarse carvedilol powder (F).

Abbreviations: PXRD, powder X-ray diffractometry; SDS, sodium dodecyl sulfate; VES, α-tocopherol succinate.

Figure 4 Dissolution profiles.

Notes: Dissolution profiles of bulk carvedilol, the commercial tablet, microsuspensions, and nanosuspensions: buffer of pH 1.0 (A); buffer of pH 6.8 (B). Each value represents the mean ± SD (n=3).

Abbreviation: CAR, carvedilol.

Figure 5 In situ absorption.

Notes: The in situ absorption of microsuspensions and nanosuspensions in rat intestinal segments compared with free carvedilol solution. *Indicates P<0.05 versus free carvedilol solution.

Abbreviation: P_eff, effective permeability.

Table 2 In vivo parameters of carvedilol microsuspensions, nanosuspensions, and the commercial tablets after oral administration (n=6)

Parameters	Microsuspensions	Nanosuspensions	Commercial tablets
Cmax (μg/mL)	1,567.52±315.10a	2,224.58±212.78a,b	1,062.61±416.26
Tmax (h)	1.31±0.74a	0.94±0.12a,b	2.75±0.71
AUC0−t (μg·h/mL)	6,815.17±1,179.66a	9,350.85±2,135.53a,b	4,498.89±1,655.72
AUC0−∞ (μg·h/mL)	7,142.17±1,241.25a	9,948.70±2,420.09a,b	4,657.86±1,727.24

Notes: All data presented in the form of mean ± SD.

a Statistically significant compared with the commercial tablet (P<0.05).

b Statistically significant compared with the microsuspensions (P<0.05).

Figure 6 Pharmacokinetics profiles.

Notes: In vivo pharmacokinetics profiles of carvedilol in beagle dogs following oral administration of commercial tablets, and microsuspension and nanosuspension capsules (n=6).

Abbreviations: MS, microsuspension; NS, nanosuspension.

Figure 7 Morphology of rat jejunum cross section.

Notes: Morphology of rat jejunum cross section after oral administration of physiological saline (A), coarse suspensions (B), and nanosuspensions (C). The magnification of the images is 200×.