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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.
Bennett-Lenane, Harriet; Jørgensen, Jacob R; Koehl, Niklas J; Henze, Laura J; O'Shea, Joseph P; Müllertz, Anette; Griffin, Brendan T.
Afiliación
  • Bennett-Lenane H; School of Pharmacy, University College Cork, Cork, Ireland.
  • Jørgensen JR; Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
  • Koehl NJ; School of Pharmacy, University College Cork, Cork, Ireland.
  • Henze LJ; School of Pharmacy, University College Cork, Cork, Ireland.
  • O'Shea JP; School of Pharmacy, University College Cork, Cork, Ireland.
  • Müllertz A; Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
  • Griffin BT; School of Pharmacy, University College Cork, Cork, Ireland. Electronic address: brendan.griffin@ucc.ie.
Eur J Pharm Sci ; 161: 105778, 2021 Jun 01.
Article en En | MEDLINE | ID: mdl-33647402
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenofibrato / Sistemas de Liberación de Medicamentos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Eur J Pharm Sci Asunto de la revista: FARMACIA / FARMACOLOGIA / QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: Irlanda Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenofibrato / Sistemas de Liberación de Medicamentos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Eur J Pharm Sci Asunto de la revista: FARMACIA / FARMACOLOGIA / QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: Irlanda Pais de publicación: Países Bajos