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Original Research

Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system

, , , &
Pages 1115-1125 | Published online: 23 Feb 2012

Figures & data

Figure 1 Chemical structure of indirubin.

Figure 1 Chemical structure of indirubin.

Table 1 Solubility of indirubin in various vehicles at 25°C

Figure 2 Ternary system containing Maisine 35-1/Cremophor EL/Transcutol P. Region of efficient self-microemulsification is bound by the solid line, and the filled circles represent compositions that were evaluated.

Figure 2 Ternary system containing Maisine 35-1/Cremophor EL/Transcutol P. Region of efficient self-microemulsification is bound by the solid line, and the filled circles represent compositions that were evaluated.

Table 2 Droplet size, polydispersibility, and solubility for the three tested SMEDDS formulations

Figure 3 In vitro indirubin concentration-time profiles from the SMEDDS formulations and S-SMEDDS with hydrophilic polymers of (A) PEG 4000, (B) HPMC, and (C) PVP K17 (n = 5).

Abbreviations: SMEDDS, self-microemulsifying drug delivery system; S-SMEDDS, supersaturatable self-microemulsifying drug delivery system; PEG, polyethylene glycol; PVP, polyvinylpyrrolidone; HPMC, hydroxypropyl methylcellulose.

Figure 3 In vitro indirubin concentration-time profiles from the SMEDDS formulations and S-SMEDDS with hydrophilic polymers of (A) PEG 4000, (B) HPMC, and (C) PVP K17 (n = 5).Abbreviations: SMEDDS, self-microemulsifying drug delivery system; S-SMEDDS, supersaturatable self-microemulsifying drug delivery system; PEG, polyethylene glycol; PVP, polyvinylpyrrolidone; HPMC, hydroxypropyl methylcellulose.

Figure 4 Molecular structures of (A) PEG 4000, (B) PVP, (C) HPMC and schematic diagram of hydrogen bonds between indirubin, (D) PEG 4000, and (E) PVP.

Abbreviations: PEG, polyethylene glycol; PVP, polyvinylpyrrolidone; HPMC, hydroxypropyl methylcellulose.

Figure 4 Molecular structures of (A) PEG 4000, (B) PVP, (C) HPMC and schematic diagram of hydrogen bonds between indirubin, (D) PEG 4000, and (E) PVP.Abbreviations: PEG, polyethylene glycol; PVP, polyvinylpyrrolidone; HPMC, hydroxypropyl methylcellulose.

Figure 5 Cumulative release profile of indirubin SMEDDS and S-SMEDDS.

Abbreviations: SMEDDS, self-microemulsifying drug delivery system; S-SMEDDS, supersaturatable self-microemulsifying drug delivery system.

Figure 5 Cumulative release profile of indirubin SMEDDS and S-SMEDDS.Abbreviations: SMEDDS, self-microemulsifying drug delivery system; S-SMEDDS, supersaturatable self-microemulsifying drug delivery system.

Figure 6 Ultra performance liquid chromatography/mass spectrometry chromatograms of (A) blank plasma, (B) blank plasma spiked with indirubin, and (C) plasma sample after oral administration of indirubin to a rat.

Figure 6 Ultra performance liquid chromatography/mass spectrometry chromatograms of (A) blank plasma, (B) blank plasma spiked with indirubin, and (C) plasma sample after oral administration of indirubin to a rat.

Figure 7 Plasma concentration profile of indirubin after oral administration of SMEDDS and S-SMEDDS in rats (n = 5).

Abbreviations: SMEDDS, self-microemulsifying drug delivery system; S-SMEDDS, supersaturatable self-microemulsifying drug delivery system.

Figure 7 Plasma concentration profile of indirubin after oral administration of SMEDDS and S-SMEDDS in rats (n = 5).Abbreviations: SMEDDS, self-microemulsifying drug delivery system; S-SMEDDS, supersaturatable self-microemulsifying drug delivery system.

Table 3 Pharmacokinetic parameters for S-SMEDDS and SMEDDS (n = 5)