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Biopharmaceutical Modeling of Drug Supersaturation During Lipid-Based Formulation Digestion Considering an Absorption Sink
- Source :
- Pharmaceutical Research. 31:3426-3444
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- In vitro lipolysis is widely utilized for predicting in vivo performance of oral lipid-based formulations (LBFs). However, evaluation of LBFs in the absence of an absorption sink may have limited in vivo relevance. This study aimed at employing biopharmaceutical modeling to simulate LBF digestion and drug supersaturation in a continuous absorptive environment.Three fenofibrate-loaded LBFs were characterized in vitro (dispersion and lipolysis) and drug precipitation was monitored using in-line Raman spectroscopy. In vitro data were combined with pharmacokinetic data derived from an in vivo study in pigs to simulate intestinal LBF transit. This biopharmaceutical model allowed calculation of lipolysis-triggered drug supersaturation while drug and lipolysis products are absorbed from the intestine.The biopharmaceutical model predicted that, in a continuous absorption environment, fenofibrate supersaturation was considerably lower compared to in vitro lipolysis (non-sink). Hence, the extensive drug precipitation observed in vitro was predicted to be unlikely in vivo. The absorption of lipolysis products increased drug supersaturation, but drug precipitation was unlikely for highly permeable drugs.Biopharmaceutical modeling is a valuable approach for predicting LBFs performance in vivo. In the absence of in vitro tools simulating absorptive conditions, modeling strategies should be further considered.
- Subjects :
- Drug
Swine
Chemistry, Pharmaceutical
Lipolysis
media_common.quotation_subject
Pharmacology toxicology
Biological Availability
Pharmaceutical Science
Spectrum Analysis, Raman
Sink (geography)
Biopharmaceutics
Fenofibrate
X-Ray Diffraction
In vivo
Animals
Pharmacology (medical)
Hypolipidemic Agents
media_common
Pharmacology
geography
Supersaturation
geography.geographical_feature_category
Chromatography
Chemistry
Organic Chemistry
Models, Theoretical
Lipids
Biopharmaceutical
Intestinal Absorption
Pharmaceutical Preparations
Molecular Medicine
Biotechnology
Subjects
Details
- ISSN :
- 1573904X and 07248741
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Pharmaceutical Research
- Accession number :
- edsair.doi.dedup.....18a43a228a0426793857ba85c9320173