Studying furosemide solubilization using an in vitro model simulating gastrointestinal digestion and drug solubilization in neonates and young infants

Klitgaard, Mette; Sassene, Philip Jonas; Selen, Arzu; Müllertz, Anette; Berthelsen, Ragna

doi:10.1016/j.ejps.2017.08.003

Cited by 18 publications

(25 citation statements)

References 24 publications

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“…In the continuous model, digestion medium was continuously pumped from a gastric to an intestinal compartment, where the concentrated medium simulating the SI fluid was present. The results suggested that the oral bioavailability of furosemide in this subpopulation increased in the presence of food . In contrast, parameter manipulation, such as simulation of food digestion and crushing of the tablets seemed to cause no alterations in the oral performance of furosemide .…”

Section: In Vitro Evaluation Of Drug Products For Paediatricsmentioning

confidence: 91%

“…The results suggested that the oral bioavailability of furosemide in this subpopulation increased in the presence of food . In contrast, parameter manipulation, such as simulation of food digestion and crushing of the tablets seemed to cause no alterations in the oral performance of furosemide . The entire furosemide dose was soluble in the aqueous phase of the simulated postprandial state, which led the authors to conclude a high bioavailability of the drug in the presence of food .…”

Section: In Vitro Evaluation Of Drug Products For Paediatricsmentioning

confidence: 97%

“…A two‐step model was proposed as more appropriate, comprising a gastric phase and an intestinal phase, where the duration of each phase, and the transfer between the two phases, should be reflective of GE and SITT in newborns/young infants. The performance of Furix ® 20 mg furosemide (BCS class II compound) tablets, in the newborn and infant GI tract was investigated with this set‐up . Fasted and fed states were simulated to represent feeding patterns in the studied population; therefore, the fasted state assumed the presence of small amounts of milk.…”

Section: In Vitro Evaluation Of Drug Products For Paediatricsmentioning

confidence: 99%

See 2 more Smart Citations

Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products – a PEARRL review

Guimarães

Statelova

Holm

et al. 2019

Journal of Pharmacy and Pharmacology

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Section: In Vitro Evaluation Of Drug Products For Paediatricsmentioning

confidence: 91%

Section: In Vitro Evaluation Of Drug Products For Paediatricsmentioning

confidence: 97%

Section: In Vitro Evaluation Of Drug Products For Paediatricsmentioning

confidence: 99%

See 1 more Smart Citation

Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products – a PEARRL review

Guimarães

Statelova

Holm

et al. 2019

Journal of Pharmacy and Pharmacology

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“…For in vitro digestion of BM, we used a previously established protocol by Klitgaard et al ( 23 ). In brief, 25 ml of BM were added to concentrated gastric medium leading to a final concentration of 3 mM NaCl, 2 mM TRIS, and 2 mM maleic acid.…”

Section: Methodsmentioning

confidence: 99%

Granulocytic Myeloid-Derived Suppressor Cells (GR-MDSC) in Breast Milk (BM); GR-MDSC Accumulate in Human BM and Modulate T-Cell and Monocyte Function

et al. 2018

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Nosocomial bacterial infections (NBI) and necrotizing enterocolitis (NEC) are among the main reasons for death in preterm infants. Both are often caused by bacteria coming from the infected infant’s gut and feeding with breast milk (BM) seems beneficial in their pathogenesis. However, mechanisms causing the protective effect of BM are only incompletely understood. Myeloid-derived suppressor cells (MDSC) are myeloid cells with suppressive activity on other immune cells, recently described to play a role in mediating maternal–fetal tolerance during pregnancy and immune adaptation in newborns. Until now, nothing is known about occurrence and function of MDSC in BM. We analyzed MDSC in BM and peripheral blood of breastfeeding mothers and found that granulocytic MDSC, but not monocytic MDSC, accumulate in BM, exhibit an activated phenotype and increased suppressive activity and modulate TLR-expression on monocytes. Furthermore, we found that the lactotrophic hormones prolactin and oxytocin do not induce MDSC from peripheral blood. This is the first study to describe MDSC with immune-modulatory properties in human BM. Our results point toward a role for MDSC in local immune modulation in the gut possibly protecting infants from NBI and NEC.

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“…Considering the drawbacks of this pH-stat lipolysis models, further research into the development of a predictive in vitro digestion model is required. In order to compensate for the problem of one-compartment model, two-step two-compartment GI digestion model simulating gastro-intestinal environment were proposed [184][185][186].…”

Section: Ph-stat Lipolysis Modelsmentioning

confidence: 99%

Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

Park

Kim

2020

Pharmaceutics

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Self-emulsifying drug delivery systems (SEDDSs) are a vital strategy to enhance the bioavailability (BA) of formulations of poorly water-soluble compounds. However, these formulations have certain limitations, including in vivo drug precipitation, poor in vitro in vivo correlation due to a lack of predictive in vitro tests, issues in handling of liquid formulation, and physico-chemical instability of drug and/or vehicle components. To overcome these limitations, which restrict the potential usage of such systems, the supersaturable SEDDSs (su-SEDDSs) have gained attention based on the fact that the inclusion of precipitation inhibitors (PIs) within SEDDSs helps maintain drug supersaturation after dispersion and digestion in the gastrointestinal tract. This improves the BA of drugs and reduces the variability of exposure. In addition, the formulation of solid su-SEDDSs has helped to overcome disadvantages of liquid or capsule dosage form. This review article discusses, in detail, the current status of su-SEDDSs that overcome the limitations of conventional SEDDSs. It discusses the definition and range of su-SEDDSs, the principle mechanisms underlying precipitation inhibition and enhanced in vivo absorption, drug application cases, biorelevance in vitro digestion models, and the development of liquid su-SEDDSs to solid dosage forms. This review also describes the effects of various physiological factors and the potential interactions between PIs and lipid, lipase or lipid digested products on the in vivo performance of su-SEDDSs. In particular, several considerations relating to the properties of PIs are discussed from various perspectives.Pharmaceutics 2020, 12, 365 2 of 57 intraluminal supersaturation and the biorelevance of supersaturation assays will be addressed. Finally, we will make suggestions for the successful development of su-SEDDs.There are many review articles that give useful information about the nature and application of supersaturable drug delivery systems or conventional SEDDSs. However, these reviews cover only a limited range of su-SEDDSs. Therefore, this review, which includes the current status of technology focused only on su-SEDDSs, is a valuable addition to the previous review literature because no review article currently covers such a wide range of su-SEDDSs. Conventional Solubilized SEDDSsThere has been a steady increase in the number of new drug candidates (almost 40%) that are highly hydrophobic and poorly water-soluble. The oral bioavailability of poorly water-soluble drugs is hindered by low solubility and slow dissolution in the aqueous environment of the GIT. Thus, it is a great challenge for pharmaceutical scientists to overcome the inherent slow dissolution and poor oral absorption of hydrophobic drugs [1][2][3][4]. SEDDSs have emerged as a promising approach to improving the biopharmaceutical performance of hydrophobic drugs by enhancing their bioavailability [5,6].An SEDDS is a pre-concentrate composed of a drug, oils, surfactants, and sometimes co-solvents and/or co-surfactan...

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Studying furosemide solubilization using an in vitro model simulating gastrointestinal digestion and drug solubilization in neonates and young infants

Cited by 18 publications

References 24 publications

Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products – a PEARRL review

Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products – a PEARRL review

Granulocytic Myeloid-Derived Suppressor Cells (GR-MDSC) in Breast Milk (BM); GR-MDSC Accumulate in Human BM and Modulate T-Cell and Monocyte Function

Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

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