Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs

Abstract

The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery.

Keywords: N-(2-hydroxy)propyl-3-trimethyl ammonium chitosan chloride; in vitro release; indomethacin; nanostructured lipid nanocarrier; poorly water soluble drug.

Figure 1

¹H-NMR spectra of (a) chitosan and (b) HTCC at 25 °C.

Figure 2

FT-IR spectra of chitosan and HTCC.

Figure 3

Zeta-potential profiles of chitosan and HTCC as a function of pH.

Figure 4

Zeta-potential profiles of different NLC formulations as a function of pH. NLC_B, blank NLC formulation; NLC_I, indomethacin loaded NLC formulation; NLC/CS_I: indomethacin loaded NLC formulation coated with chitosan; NLC/HTCC_I, indomethacin loaded NLC formulation coated with HTCC.

Figure 5

Endothermic peaks of (a) bulk glyceryl monostearate, indomethacin, and their mixture and (b) NLC formulations; *G, endothermic peak of glyceryl monostearate; *I, endothermic peak of indomethacin.

Figure 6

In vitro release profiles of three different indomethacin loaded NLC formulations. NLC_I, indomethacin loaded NLC formulation; NLC/CS_I: indomethacin loaded NLC formulation coated with chitosan; NLC/HTCC_I, indomethacin loaded NLC formulation coated with HTCC. Each formulation was fitted according to Korsmeyer-Peppas regression model except pure indomethacin.

Figure 7

In vitro digestion characteristics of three different indomethacin loaded NLC formulations. NLC_I, indomethacin loaded NLC formulation; NLC/CS_I: indomethacin loaded NLC formulation coated with chitosan; NLC/HTCC_I, indomethacin loaded NLC formulation coated with HTCC.