4.Studies with different patients using magnetic resonance imaging
show that a dose of water with a volume varying between about 240
and 250 mL empties rapidly from the fasted human stomach, with a half
emptying time (T50%) between approximately 13 and 18 min and
complete gastric emptying in 45 min (Mudie et al. 2014, Steingoetter
et al. 2006).Although the release results of our formulation were different, it is
important to consider that gastrintestinal conditions (GI) can differ
among patients and therefore a variety of inter- and intra-individual
differences in GI physiology have been reported in the literature, such
as variations in gastric emptying, intestinal transit times, composition
and volume of fluid available in the different GI sections and in GI
motility patterns in both fasted and fed state dosing conditions
Table 3
Physicochemical characterization of the formulations before and after enteric coating.It is worth mentioning that
in preliminary studies we tested larger concentrations of enteric coating
polymer, however, it was observed that they reduced the EE of the drug
and the decision was thereby made to use 0.03%, which was able to
maintain the characteristics of the formulation.In vitro release
The purpose of EL100-55 as an enteric coating is to delay the exposure of OME to an acidic environment, avoiding significant degradation of the drug as well as preventing the reduction of bioavailability (Tawfeek et al. 2017).The in vitro drug release test was carried
out for the OERS/EL nanoparticles in simulated gastric fluid (pH 1.2)
for 60 min based on the residence time of the formulation in the stomach (Mudie et al. 2014, Steingoetter et al. 2006).Taking into account that OME is administered fasted and at
a half emptying time (T50%), in these conditions and with ranges from
13 to 18 min to be completed at a maximum of 45 min arises the
suggestion that the nanoparticles proposed in this study arrive at the
intestinal transit in less than 1 h, ensuring that less than 10% is released
into the stomach. A study that developed nanoparticles of OME using the emulsion
diffusion method and EL100-55 as an enteric coating polymer showed
less than 10% drug degradation in 0.1 N HCl solution (Hao et al.
2013a).This release behavior
can be explained by the pH influence on the EL100-55 polymer solubility and by the ionization of the methacrylic acid carboxylic groups in
aqueous medium (pH >= 5.5) (Sauer et al. 2009).Sample D[4,3](v) (nm) Span(v) z-average (nm) PDI EE (%) pH
OERS 175 +- 3.51a 2.26 +- 0.20a 166 +- 7.21a 0.213 +- 5.00a 95.8 8.7 +- 0.22a
OERS/EL 223 +- 13.05b 2.16 +- 0.20a 174 +- 17.00a 0.229 +- 0.01a 68.1 10.4 +- 0.36b
Matching letters within a column indicate no statistical difference (p >= 0.05).Fig. 3). 3).In this study, 0.03% was
used.1.