Andrographolide Liquisolid using Porous-Starch as the Adsorbent with Enhanced Oral Bioavailability in Rats

Abstract

Andrographolide (AGL) is the major component of Andrographispaniculata. The poor water solubility and low dissolution strongly affect its oral absorption. Liquisolid technology has been used to improve its dissolution and oral bioavailability. Liquisolid powders of AGL (AGL-LS-PSG) were obtained by firstly dissolving AGL in the mixture of NMP, PEG 6000 and Soluplus®, and solidified by absorption of the blend in porous starch. Angle of repose, Carr index and Hauser ratio presented good powder fluidity and compressibility characteristics of AGL-LS-PSG. The results of optical microscopic observation, PXRD and DSC analysis indicated that AGL has been completely adsorbed in porous starch granules and existed in an amorphous or molecularly dispersing state. AGL-LS-PSG can obviously increase the drug dissolution rate compared to commercial guttate pills and raw drug. In vivo pharmacokinetic behavior of AGL-LS-PSG was investigated following a single oral administration to rats. The C_max (0.37 ± 0.06 μg mL^-1) and AUC_0-2h (13.55 ± 2.67 μg h mL^-1) of AGL-LS-PSG were evidently increased compared to commercial guttate pills (C_max = 0.30 ± 0.21 μg mL^-1, AUC_0-2h = 9.88 ± 3.57 μg h mL^-1). This study indicated great potential of liquisolid technology in effectively improving the dissolution and bioavailability of AGL.

Keywords: Andrographolide; Bioavailability; Liquisolid technology; Porous-starch, N-methyl pyrrolidone.