Effect of Polyoxyl 35 Castor Oil and Polysorbate 80 on the Intestinal Absorption of Digoxin in vitro

One of the main goals of in silico Caco-2 cell permeability models is to identify those drug substances with high intestinal absorption in human (HIA). For more than a decade, several in silico Caco-2 models have been made, applying a wide range of modeling techniques; nevertheless, their capacity for intestinal absorption extrapolation is still doubtful. There are three main problems related to the modest capacity of obtained models, including the existence of inter- and/or intra-laboratory variability of recollected data, the influence of the metabolism mechanism, and the inconsistent in vitro-in vivo correlation (IVIVC) of Caco-2 cell permeability. This review paper intends to sum up the recent advances and limitations of current modeling approaches, and revealed some possible solutions to improve the applicability of in silico Caco-2 permeability models for absorption property profiling, taking into account the above-mentioned issues.

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Intestinal absorption of octreotide: N‐trimethyl chitosan chloride (TMC) ameliorates the permeability and absorption properties of the somatostatin analogue in vitro and in vivo

Journal of Pharmaceutical Sciences ◽

10.1002/1520-6017(200007)89:7<951::aid-jps13>3.3.co;2-t ◽

2000 ◽

Vol 89 (7) ◽

pp. 951-957

Author(s):

M. Thanou ◽

J. C. Verhoef ◽

P. Marbach ◽

H. E. Junginger

Keyword(s):

Intestinal Absorption ◽

Somatostatin Analogue ◽

Absorption Properties ◽

Trimethyl Chitosan

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Formulation and in vitro evaluation of self-nanoemulsifying liquisolid tablets of furosemide

Scientific Reports ◽

10.1038/s41598-020-79940-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lena Dalal ◽

Abdul Wahab Allaf ◽

Hind El-Zein

Keyword(s):

Theoretical Model ◽

Castor Oil ◽

In Vivo Studies ◽

Coating Materials ◽

Peg 400 ◽

The Mean ◽

Usp Apparatus ◽

Solid System

AbstractSelf-nanoemulsifying drug delivery systems (SNEDDS) were used to enhance the dissolution rate of furosemide as a model for class IV drugs and the system was solidified into liquisolid tablets. SNEDDS of furosemide contained 10% Castor oil, 60% Cremophor EL, and 30% PEG 400. The mean droplets size was 17.9 ± 4.5 nm. The theoretical model was used to calculate the amounts of the carrier (Avicel PH101) and coating materials (Aerosil 200) to prepare liquisolid powder. Carrier/coating materials ratio of 5/1 was used and Ludipress was added to the solid system, thus tablets with hardness of 45 ± 2 N were obtained. Liquisolid tablets showed 2-folds increase in drug release as compared to the generic tablets after 60 min in HCl 0.1 N using USP apparatus-II. Furosemide loaded SNEDDS tablets have great prospects for further in vivo studies, and the theoretical model is useful for calculating the adequate amounts of adsorbents required to solidify these systems.

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New In Vitro Coculture Model for Evaluating Intestinal Absorption of Different Lipid Nanocapsules

Pharmaceutics ◽

10.3390/pharmaceutics13050595 ◽

2021 ◽

Vol 13 (5) ◽

pp. 595

Author(s):

Norraseth Kaeokhamloed ◽

Emillie Roger ◽

Jérôme Béjaud ◽

Nolwenn Lautram ◽

Florence Manero ◽

...

Keyword(s):

Surface Modification ◽

Intestinal Absorption ◽

Oral Absorption ◽

Membrane Integrity ◽

Microvascular Endothelial Cell ◽

Absorption Mechanism ◽

Apparent Permeability ◽

Lipid Nanocapsules ◽

Coculture Model

Standard models used for evaluating the absorption of nanoparticles like Caco-2 ignore the presence of vascular endothelium, which is a part of the intestinal multi-layered barrier structure. Therefore, a coculture between the Caco-2 epithelium and HMEC-1 (Human Microvascular Endothelial Cell type 1) on a Transwell® insert has been developed. The model has been validated for (a) membrane morphology by transmission electron microscope (TEM); (b) ZO-1 and β-catenin expression by immunoassay; (c) membrane integrity by trans-epithelial electrical resistance (TEER) measurement; and (d) apparent permeability of drugs from different biopharmaceutical classification system (BCS) classes. Lipid nanocapsules (LNCs) were formulated with different sizes (55 and 85 nm) and surface modifications (DSPE-mPEG (2000) and stearylamine). Nanocapsule integrity and particle concentration were monitored using the Förster resonance energy transfer (FRET) technique. The result showed that surface modification by DSPE-mPEG (2000) increased the absorption of 55-nm LNCs in the coculture model but not in the Caco-2. Summarily, the coculture model was validated as a tool for evaluating the intestinal absorption of drugs and nanoparticles. The new coculture model has a different LNCs absorption mechanism suggesting the importance of intestinal endothelium and reveals that the surface modification of LNCs can modify the in vitro oral absorption.

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Food emulsifier polysorbate 80 promotes the intestinal absorption of mono-2-ethylhexyl phthalate by disturbing intestinal barrier

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2021.115411 ◽

2021 ◽

Vol 414 ◽

pp. 115411

Author(s):

Yu-Ting Zhu ◽

Yi-Zhen Yuan ◽

Qiu-Ping Feng ◽

Meng-Yuan Hu ◽

Wen-Jie Li ◽

...

Keyword(s):

Intestinal Absorption ◽

Intestinal Barrier ◽

Polysorbate 80 ◽

Food Emulsifier ◽

Ethylhexyl Phthalate

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Effect Of Solvents On Indium-111 Oxine Transport In Human Platelets And On Platelet Function In Vitro

10.1055/s-0038-1653277 ◽

1981 ◽

Author(s):

T Tsukada

Keyword(s):

Platelet Function ◽

Kinetic Constant ◽

Inhibitory Effect ◽

Human Platelets ◽

Polysorbate 80 ◽

Autologous Plasma ◽

Indium 111 ◽

Induced Aggregation ◽

Water Space

Mechanism of Indium-111 oxine(In) transport in human platelets in buffered saline and the effect of In-labeling on platelet function were studied using In dissolved in 25% of ethanol in saline (In-ES) or 0.01% of polysorbate 80 in HEPES buffer(In-PH). Increase in temperature up to 37° C progressively enhanced the transport of In-ES, while transport of In-PH reached to plateau at 15°C. A states of equilibrium was not reached during 2 hr incubation at 22°C in In-ES. Uptake of In-PH reached to plateau after only 15 min of incubation. Distribution of In taken up by platelets in InES was 57% in cytosol and 27% in stroma, while in In-PH 69% in stroma and 22% in cytosol. 88% of In in cytosol was bound to lipids(46% in cholesterol and 27% in PS+PI). 82% of In in stroma was found in PS+PI fraction.The fact that the ratio of free In between the platelet water space and the outside medium after 30 min of incubation at up to 0.1 uM of In exceeded unity, suggests satura- , ble component of In transport prevails at this concentration in In-ES and In-PH. Kinetic constant could be calculated, Kt= 2nM, Vmax= 2.5 pmol/min/ml in In-ES, and Kt= InM, Vmax=0.7 pmol/min/ml in In-PH.Elution of In from radiolableled platelets in autologous plasma incubated at 37°C for 5 hr was less than 10% in the case of In-ES and 56% in the case of In-PH. Less than 3% of labeled-In was eluated from platelets in collagen-induced aggregation and 4-7% of In was eluated in thrombin-induced aggregation.Although 0.3% of ethanol and/or 6nM of oxine have no inhibitory effect of platelet aggregation, collagen-induced aggregation and release reaction of In-labeled platelet was impaired. 0.003% of polysorbate 80 itself abolished completely the aggregability of platelets by collagen or thrombin.It is concluded In-PH is unsuitable for platelet labeling. In-111 oxine also seems to have problems which Cr-51 has, i.e. inhomogenous distribution of In in a platelet population, elution of In from labeled platelets in circulation.

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