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<i>In Vivo</i> Precipitation of Poorly Soluble Drugs from Lipid-Based Drug Delivery Systems

2016· article· en· W2515297195 on OpenAlexafffund
Philip Sassene, Maria Høtoft Michaelsen, Mette Dalskov Mosgaard, Mette Kristine Rask Jensen, Esther van den Broek, Kishor M. Wasan, Huiling Mu, Thomas Rades, Anette Müllertz

Bibliographic record

VenueMolecular Pharmaceutics · 2016
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicDrug Solubulity and Delivery Systems
Canadian institutionsUniversity of SaskatchewanUniversity of British Columbia
FundersCanadian Institutes of Health ResearchEuropean CommissionEuropean Federation of Pharmaceutical Industries and Associations
KeywordsIn vivoStomachFenofibrateLipolysisSmall intestinePharmacologyDanazolDrugChemistryPrecipitationMedicineInternal medicineBiologyAdipose tissue

Abstract

fetched live from OpenAlex

Precipitation of poorly water-soluble drugs from lipid-based drug delivery systems (LbDDS) has been studied extensively during in vitro lipolysis but has never been shown in vivo. The aim of this study was therefore to investigate if drug precipitation can occur from LbDDS during transit of the gastrointestinal tract in vivo. Rats were administered 300 μL of either of two LbDDS (LbDDS I and LbDDS II) loaded with danazol or fenofibrate (or paracetamol to assess gastric emptying). The rats were euthanized at various time points after administration of both LbDDS containing either drug, and the contents of the stomach and proximal part of the small intestine were harvested. The contents were analyzed for crystalline drug by X-ray powder diffraction and polarized light microscopy. No drug precipitation was evident in the stomach or the intestine after administration of LbDDS I containing danazol at the tested time points. Fenofibrate precipitation was absent in the stomach initially after administration of LbDDS I, but was evident in the stomach 90 min after dosing. No crystalline fenofibrate was observed in the intestine. Danazol and fenofibrate precipitation was evident in the stomach following administration of LbDDS II containing either drug, but not in the intestine at the tested time point. Drug precipitation from LbDDS was observed in the stomach, but not in the intestine, which is contrary to what in vitro lipolysis data (obtained under human GI conditions) suggests. Thus, precipitation of drugs from LbDDS in vivo in rats is much lower than might be anticipated from in vitro lipolysis data.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.050
GPT teacher head0.362
Teacher spread0.312 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations35
Published2016
Admission routes2
Has abstractyes

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