Electrosprayed Nanosystems of Carbamazepine - PVP K30 for Enhancing Its Pharmacologic Effects

Abstract

This study was conducted to enhance the pharmacologic effect of carbamazepine (CBZ) (as a poorly water-soluble drug) by fabricating CBZ-PVP K30 nanobeads using an electrospraying technique. CBZ-PVP K30 nanosystems with various ratios (1:3 and 1:5) at total solution concentrations of 3% and 5% w/v were prepared. The solution concentration extremely affected the size of the samples; where, the nanobeads (mean diameter of 457.65 ± 113.72 nm and 1.16 ± 0.46 µm) were developed at low and high solution concentrations, respectively. DSC thermographs and PXRD patterns precisely showed CBZ amorphization in the electrosprayed nanosystems. Based on the FTIR spectrum of the electrosprayed samples, a feasible interaction between N-H/O-H group of CBZ and PVP carbonyl group was detected. The in-vitro release studies revealed that the electrosprayed nanosystems represent a comparable rapid dissolution rate with respect to the physical mixtures (PMs) and the pure drug. The in-vivo results in NMRI mice indicated that the electrosprayed nanoformulation (with the drug: polymer ratio of 1:5 at a total solution concentration of 5% (w/v)) prolonged seizure latency time and decreased mortality percent in strychnine (STR) induced seizure mice more efficiently than the PM. Our finding revealed that the electrospraying as a cost-benefit and one step technique could be effectively applied for improving the physicochemical characteristics and pharmacologic effect of CBZ.

Keywords: Carbamazepine; Electrospray; In-vivo evaluation; Nanobeads; PVP K30.

Figure 1

FE-SEM images of the carbamazepine – PVP K30 electrosprayed nanosystems with (a) drug: polymer ratio of 1:3 at the total solution concentration of 3% w/v (Magnification: ×50 k), (b) 1:3-5% w/v (×17 k), (c) 1:5-3% w/v (×15 k) and (d) 1:5-5% w/v (×17 k).

Figure 2

DSC thermograms of the pure carbamazepine (CBZ), PVP K30, physical mixture (PM) and electrosprayed nanosystems (ES) with the drug: polymer ratio of 1:3 at total solution concentrations of 3% and 5% (w/v).

Figure 3

PXRD patterns of the pure carbamazepine (CBZ), PVP K30, physical mixture (PM) and electrosprayed nanosystems (ES) with the drug: polymer ratio of 1:3 at total solution concentrations of 3% and 5% (w/v).

Figure 4

FTIR curves of the pure carbamazepine (CBZ), PVP K30, physical mixture (PM) and electrosprayed nanosystems (ES) with the drug: polymer ratio of 1:3 at total solution concentrations of 3% and 5% (w/v).

Figure 5

Dissolution profiles of the pure carbamazepine (CBZ), physical mixtures (PM) with drug: polymer ratios of 1:3 and 1:5, and electrosprayed nanosystems (ES) with the drug: polymer ratios of 1:3 and 1:5 at total solution concentrations of 3%, and 5% (w/v).