Drug solubilization during simulated pediatric gastro-intestinal digestion
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Drug solubilization during simulated pediatric gastro-intestinal digestion. / Kofoed-Djursner, Caroline; Jamil, Ali; Selen, Arzu; Mullertz, Anette; Berthelsen, Ragna.
In: European Journal of Pharmaceutical Sciences, Vol. 162, 105828, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Drug solubilization during simulated pediatric gastro-intestinal digestion
AU - Kofoed-Djursner, Caroline
AU - Jamil, Ali
AU - Selen, Arzu
AU - Mullertz, Anette
AU - Berthelsen, Ragna
PY - 2021
Y1 - 2021
N2 - To increase the understanding of how drugs behave following oral administration to the pediatric population, the aim of the present study was to investigate the solubilization of fluconazole and ibuprofen during simulated gastro-intestinal (GI) digestion, using an immediate transfer model mimicking pediatric GI digestion. The effects of infant formula and digestion, on the drug solubilization, were studied using simulated fasted and fed state digestion media in the presence and absence of digestive enzymes. Additionally, the effect of digestion media viscosity on the solubilization process was investigated. It was found that the solubilization of fluconazole was unaffected by all tested parameters, as the entire estimated dose equivalent was solubilized in the aqueous phase throughout all digestion studies. In contrast, the solubilization of ibuprofen was affected by all the tested parameters, i.e. in the fasted state, the solubilization of ibuprofen was limited by its solubility in the aqueous phase of the simulated GI digestion media, whereas the solubilization in the fed state was affected by drug partitioning between the lipid and the aqueous phases, and therefore by the digestion of the lipid phase. Adding Nestle ' Thicken UpTM, containing xanthan gum as a thickening agent, to the digestion medium increased its viscosity, which in turn resulted in a reduced initial digestion rate, increased pH fluctuations, as well as high variability in all drug solubilization data as evident in large standard deviations. Furthermore, the increased digestion medium viscosity decreased the drug recovery from the combined pellet and aqueous phase. The observed viscosity effects might translate into a more variable and lower oral bioavailability.
AB - To increase the understanding of how drugs behave following oral administration to the pediatric population, the aim of the present study was to investigate the solubilization of fluconazole and ibuprofen during simulated gastro-intestinal (GI) digestion, using an immediate transfer model mimicking pediatric GI digestion. The effects of infant formula and digestion, on the drug solubilization, were studied using simulated fasted and fed state digestion media in the presence and absence of digestive enzymes. Additionally, the effect of digestion media viscosity on the solubilization process was investigated. It was found that the solubilization of fluconazole was unaffected by all tested parameters, as the entire estimated dose equivalent was solubilized in the aqueous phase throughout all digestion studies. In contrast, the solubilization of ibuprofen was affected by all the tested parameters, i.e. in the fasted state, the solubilization of ibuprofen was limited by its solubility in the aqueous phase of the simulated GI digestion media, whereas the solubilization in the fed state was affected by drug partitioning between the lipid and the aqueous phases, and therefore by the digestion of the lipid phase. Adding Nestle ' Thicken UpTM, containing xanthan gum as a thickening agent, to the digestion medium increased its viscosity, which in turn resulted in a reduced initial digestion rate, increased pH fluctuations, as well as high variability in all drug solubilization data as evident in large standard deviations. Furthermore, the increased digestion medium viscosity decreased the drug recovery from the combined pellet and aqueous phase. The observed viscosity effects might translate into a more variable and lower oral bioavailability.
KW - Pediatrics
KW - Drug delivery
KW - In vitro model
KW - Digestion
KW - Solubilization
KW - Ibuprofen
KW - Fluconazole
KW - IBUPROFEN
KW - CLASSIFICATION
KW - FLUCONAZOLE
KW - PH
KW - PHARMACOKINETICS
KW - FORMULATION
KW - ABSORPTION
KW - MEDICINES
KW - CHILDREN
KW - WORKING
U2 - 10.1016/j.ejps.2021.105828
DO - 10.1016/j.ejps.2021.105828
M3 - Journal article
C2 - 33819625
VL - 162
JO - Norvegica Pharmaceutica Acta
JF - Norvegica Pharmaceutica Acta
SN - 0928-0987
M1 - 105828
ER -
ID: 272419320