Exploring Porcine Gastric and Intestinal Fluids using Microscopic and Solubility Estimates:Impact of Placebo Self-Emulsifying Drug Delivery System Administration to Inform Bio-Predictive in vitro Tools
| Autor: | Laura J. Henze, Joseph P. O'Shea, Jacob Rune Jørgensen, Niklas J. Koehl, Harriet Bennett-Lenane, Anette Müllertz, Brendan T. Griffin |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Drug
Swine media_common.quotation_subject Pharmaceutical Science Self emulsifying Administration Oral Biological Availability 02 engineering and technology Pharmacology Placebo 030226 pharmacology & pharmacy Landrace pigs 03 medical and health sciences 0302 clinical medicine Drug Delivery Systems Fenofibrate medicine Animals Solubility media_common Chemistry 021001 nanoscience & nanotechnology In vitro In vitro tools Drug delivery Oral drug delivery Emulsions 0210 nano-technology Bio-enabling formulations Ex vivo medicine.drug |
| Zdroj: | Bennett-Lenane, H, Jørgensen, J R, Koehl, N J, Henze, L J, O'Shea, J P, Müllertz, A & Griffin, B T 2021, ' Exploring Porcine Gastric and Intestinal Fluids using Microscopic and Solubility Estimates : Impact of Placebo Self-Emulsifying Drug Delivery System Administration to Inform Bio-Predictive in vitro Tools ', European Journal of Pharmaceutical Sciences, vol. 161, 105778 . https://doi.org/10.1016/j.ejps.2021.105778 |
| DOI: | 10.1016/j.ejps.2021.105778 |
| Popis: | Validation and characterisation of in vitro and pre-clinical animal models to support bio-enabling formulation development is of paramount importance. In this work, post-mortem gastric and small intestinal fluids were collected in the fasted, fed state and at five sample-points post administration of a placebo Self-Emulsifying Drug Delivery System (SEDDS) in the fasted state to pigs. Cryo-TEM and Negative Stain-TEM were used for ultrastructure characterisation. Ex vivo solubility of fenofibrate was determined in the fasted-state, fed-state and post-SEDDS administration. Highest observed ex vivo drug solubility in intestinal fluids after SEDDS administration was used for optimising the biorelevant in vitro conditions to determine maximum solubility. Under microscopic evaluation, fasted, fed and SEDDS fluids resulted in different colloidal structures. Drug solubility appeared highest 1 hour post SEDDS administration, corresponding with presence of SEDDS lipid droplets. A 1:200 dispersion of SEDDS in biorelevant media matched the highest observed ex vivo solubility upon SEDDS administration. Overall, impacts of this study include increasing evidence for the pig preclinical model to mimic drug solubility in humans, observations that SEDDS administration may poorly mimic colloidal structures observed under fed state, while microscopic and solubility porcine assessments provided a framework for increasingly bio-predictive in vitro tools. |
| Databáze: | OpenAIRE |
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