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Original Research

Development and mechanistic study of a microemulsion containing vitamin E TPGS for the enhancement of oral absorption of celecoxib

Pages 3087-3102 | Published online: 30 Apr 2019

Figures & data

Table 1 Solubility of celecoxib in various oils and cosurfactants

short-legendFigure 1

Table 2 Formulations, component ratios, celecoxib solubilities and concentrations of celecoxib loaded in microemulsions

Table 3 Particle size, zeta potential, polydispersity index (PDI) and electrical conductivity of microemulsions (MEs) without celecoxib (blank MEs) and celecoxib-loaded microemulsions (celecoxib-loaded MEs)

Figure 2 The rheological properties of celecoxib-loaded ME-1(

), celecoxib-loaded ME-2(
), celecoxib-loaded ME-3(
), celecoxib-loaded ME-4(
) and celecoxib-loaded ME-5 (
). All data represent the mean±standard deviation (n=3).

Figure 2 The rheological properties of celecoxib-loaded ME-1(Display full size), celecoxib-loaded ME-2(Display full size), celecoxib-loaded ME-3(Display full size), celecoxib-loaded ME-4(Display full size) and celecoxib-loaded ME-5 (Display full size). All data represent the mean±standard deviation (n=3).

Table 4 In vitro release kinetics of celecoxib in PEG 400 and celecoxib-loaded microemulsions (ME)

Figure 3 In vitro cumulative release profiles (%) of celecoxib from PEG 400 (

) and the following microemulsion formulations: ME-1(
), ME-2 (
), ME-3 (
), ME-4 (
) and ME-5 (
). All data represent the mean±standard deviation (n=3).

Figure 3 In vitro cumulative release profiles (%) of celecoxib from PEG 400 (Display full size) and the following microemulsion formulations: ME-1(Display full size), ME-2 (Display full size), ME-3 (Display full size), ME-4 (Display full size) and ME-5 (Display full size). All data represent the mean±standard deviation (n=3).

Table 5 The apparent permeability (Papp) of celecoxib from the control (PEG 400) and microemulsions (ME)

Figure 4 In vitro cumulative intestinal absorption profiles of celecoxib from PEG 400 (

) and the following microemulsion formulations: ME-1(
), ME-2 (
), ME-3 (
), ME-4 (
) and ME-5 (
). All data represent the mean±standard deviation (n=3).

Figure 4 In vitro cumulative intestinal absorption profiles of celecoxib from PEG 400 (Display full size) and the following microemulsion formulations: ME-1(Display full size), ME-2 (Display full size), ME-3 (Display full size), ME-4 (Display full size) and ME-5 (Display full size). All data represent the mean±standard deviation (n=3).

Table 6 The percent cytotoxicity of blank ME-4, celecoxib-loaded ME-4, blank PEG 400 and celecoxib in PEG 400

Figure 5 CLSM images show x-z plane sequential penetration of a porcine intestine treated with (A) Nile red in PEG 400 and (B) Nile red-loaded ME-4 after 3 h. Scale bar represents 50 µm. (C) Comparison of the fluorescence intensity profiles of Nile red at various depths in the intestine shown in Figure 5a (

) and Figure 5b (
). All data represent the mean±standard deviation.

Abbreviation: A.U., arbitrary units.

Figure 5 CLSM images show x-z plane sequential penetration of a porcine intestine treated with (A) Nile red in PEG 400 and (B) Nile red-loaded ME-4 after 3 h. Scale bar represents 50 µm. (C) Comparison of the fluorescence intensity profiles of Nile red at various depths in the intestine shown in Figure 5a (Display full size) and Figure 5b (Display full size). All data represent the mean±standard deviation.Abbreviation: A.U., arbitrary units.

Figure 6 (A) Schematic representation of Nile red-loaded NBD-PE-labeled microemulsion particles and (B) CLSM image of an intact porcine intestine cross section stained with DAPI. MCT oil = medium-chain triglycerides oil. The scale bar represents 50 µm.

Figure 6 (A) Schematic representation of Nile red-loaded NBD-PE-labeled microemulsion particles and (B) CLSM image of an intact porcine intestine cross section stained with DAPI. MCT oil = medium-chain triglycerides oil. The scale bar represents 50 µm.

Figure 7 CLSM (x–y plane) images show a porcine intestine treated with Nile red-loaded NBD-PE-labeled microemulsion after (A) 2 h and (B) 4 h. Each image is divided into three frames as follows: (1) red fluorescence of Nile red, (2) green fluorescence of NBD-PE-labeled microemulsion particles and (3) overlay of 1 and 2. The scale bar represents 50 µm. The dash circles indicate a group of microemulsion particles from which the entrapped drugs were released into the tissues.

Figure 7 CLSM (x–y plane) images show a porcine intestine treated with Nile red-loaded NBD-PE-labeled microemulsion after (A) 2 h and (B) 4 h. Each image is divided into three frames as follows: (1) red fluorescence of Nile red, (2) green fluorescence of NBD-PE-labeled microemulsion particles and (3) overlay of 1 and 2. The scale bar represents 50 µm. The dash circles indicate a group of microemulsion particles from which the entrapped drugs were released into the tissues.

Figure 8 CLSM images show a cross-section image of a porcine intestine stained with DAPI and treated with Nile red-loaded NBD-PE-labeled microemulsion particles after 4 h from different areas (A) and (B). Each image is divided into four frames as follows: (1) red fluorescence of Nile red, (2) green fluorescence of NBD-PE, (3) blue fluorescence of DAPI and (4) overlay of 1, 2 and 3. The scale bar represents 50 µm and 100 µm for A and B, respectively.

Figure 8 CLSM images show a cross-section image of a porcine intestine stained with DAPI and treated with Nile red-loaded NBD-PE-labeled microemulsion particles after 4 h from different areas (A) and (B). Each image is divided into four frames as follows: (1) red fluorescence of Nile red, (2) green fluorescence of NBD-PE, (3) blue fluorescence of DAPI and (4) overlay of 1, 2 and 3. The scale bar represents 50 µm and 100 µm for A and B, respectively.

Table 7 Transepithelial electrical resistance (TEER) of porcine intestines before and after treatment with PBS, celecoxib in PEG 400 and celecoxib-loaded ME-4