Development of a Novel Bilosomal System for Improved Oral Bioavailability of Sertraline Hydrochloride: Formulation Design, In Vitro Characterization, and Ex Vivo and In Vivo Studies
Abstract:This study was proposed to develop an optimized sertraline hydrochloride (SER)–loaded bilosomal system and evaluate its potential for enhancement of drug oral bioavailability. A full 23 factorial design was used to prepare SER-loaded bilosomal dispersions by thin film hydration using span 60, cholesterol (CHL), and sodium deoxycholate (SDC). The investigated factors included the total concentration of span 60 and CHL (X1), span 60:CHL molar ratio (X2), and SER:SDC molar ratio (X3). The studied responses were e… Show more
“…Different thermal behaviours of DA may be attributed to the various molecular arrangements resulting from the strong intermolecular interaction. As reported previously, [49] the exothermic peak at around 180°C was attributed to the recrystallization, and the endothermic reactions were related to the intermolecular separation-melting. The DSC diagram of recrystallized DA-RC was slightly different from that of DA alone.…”
Section: Interlayer Arrangementsupporting
confidence: 78%
“…The DA as it is showed one distinct exothermic peak at 184°C and two endothermic peaks at 235 and 353°C, respectively ( figure 8 a ). According to the previous literature, deoxycholic acid showed various behaviours with respect to temperature [ 46 – 49 ]. Some papers reported the endothermic behaviour of DA at around 200°C due to melting; [ 46 , 47 ] other papers observed step-by-step exothermic and endothermic behaviours upon temperature increase [ 48 ].…”
Deoxycholate (DA) is a natural emulsifying agent involved in the absorption of dietary lipids. Due to the facial distribution of hydrophobic-hydrophilic region, DA easily aggregates under ambient conditions, and this property hinders the practical application of DA in clinical applications. In this study, we found that the molecular arrangement of DA molecules could be controlled by using layered double hydroxide (LDH) under a specific reaction condition. The effect of reaction methods such as co-precipitation, ion exchange and reconstruction on the molecular arrangement of DA was investigated by X-ray diffraction, Fourier-transform infrared spectroscopy, high-resolution transmission electron microscopy and differential scanning calorimetry. It was demonstrated that the self-aggregation of DA molecules could be suppressed by the oriented arrangement of DA between the gallery space of LDH. The DA moiety was well stabilized in the LDH layers due to the electrostatic interaction between DA molecules and LDH layers. The most ordered arrangement of DA molecules was observed when DA was incorporated into LDH via a reconstruction method. The DA molecules arranged in LDH via reconstruction did not show significant exothermic or endothermic behaviour up to 400°C, showing that the DA moiety lost its intermolecular attraction in between LDH layers.
“…Different thermal behaviours of DA may be attributed to the various molecular arrangements resulting from the strong intermolecular interaction. As reported previously, [49] the exothermic peak at around 180°C was attributed to the recrystallization, and the endothermic reactions were related to the intermolecular separation-melting. The DSC diagram of recrystallized DA-RC was slightly different from that of DA alone.…”
Section: Interlayer Arrangementsupporting
confidence: 78%
“…The DA as it is showed one distinct exothermic peak at 184°C and two endothermic peaks at 235 and 353°C, respectively ( figure 8 a ). According to the previous literature, deoxycholic acid showed various behaviours with respect to temperature [ 46 – 49 ]. Some papers reported the endothermic behaviour of DA at around 200°C due to melting; [ 46 , 47 ] other papers observed step-by-step exothermic and endothermic behaviours upon temperature increase [ 48 ].…”
Deoxycholate (DA) is a natural emulsifying agent involved in the absorption of dietary lipids. Due to the facial distribution of hydrophobic-hydrophilic region, DA easily aggregates under ambient conditions, and this property hinders the practical application of DA in clinical applications. In this study, we found that the molecular arrangement of DA molecules could be controlled by using layered double hydroxide (LDH) under a specific reaction condition. The effect of reaction methods such as co-precipitation, ion exchange and reconstruction on the molecular arrangement of DA was investigated by X-ray diffraction, Fourier-transform infrared spectroscopy, high-resolution transmission electron microscopy and differential scanning calorimetry. It was demonstrated that the self-aggregation of DA molecules could be suppressed by the oriented arrangement of DA between the gallery space of LDH. The DA moiety was well stabilized in the LDH layers due to the electrostatic interaction between DA molecules and LDH layers. The most ordered arrangement of DA molecules was observed when DA was incorporated into LDH via a reconstruction method. The DA molecules arranged in LDH via reconstruction did not show significant exothermic or endothermic behaviour up to 400°C, showing that the DA moiety lost its intermolecular attraction in between LDH layers.
“…Bile salts give an elastic quality to the vesicles and act as permeability enhancers increasing biological barriers' fluidity, which include the intestinal membrane, thus facilitating the drug penetration across it. 49,50 Figure 6.The intestinal permeation behavior of chrysin from its related suspension and the optimized bilosomes formulation.…”
In the present work, chrysin loaded bilosomes were formulated, characterized and evaluated to enhance the hepatoprotective activity of drug. Accordingly, chrysin loaded bilosomes were prepared by applying the thin film hydration method; also, fractional factorial design was used to optimize the production conditions of nanoformulations. The prepared formulations were subjected to different methods of characterization; then the hepatoprotective activity of the optimized one was evaluated in the CCl4 hepatointoxicated mice model. Optimized chrysin loaded bilosomes showed a spherical shape with a particle size of 232.97 ± 23 nm, the polydispersity index of 0.35 ± 0.01, the zeta potential of −44.5 ± 1.27 mv, the entrapment efficiency of 96.77 ± 0.18%, the drug loading % of 6.46 ± 0.01 and the release efficiency of 42.25 ± 1.04 during 48 h. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assay demonstrated the superiority of the anti-oxidant potential of chrysin loaded bilosomes, as compared to pure chrysin. This was in agreement with histopathological investigations, showing significant improvement in serum hepatic biomarkers of CCl4 intoxicated mice treated with chrysin loaded bilosomes, as compared with free chrysin. These results, thus, showed the potential use of bilosomes to enhance the hepatoprotective activity of chrysin via oral administration.
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