Evaluation and Refinement of the Bovine Cornea Opacity and Permeability Assay

In this study, the amino acid arginine (ARG) and P-glycoprotein (P-gp) inhibitors verapamil hydrochloride (VER), piperine (PIP) and quercetin (QRT) were used as co-formers for co-amorphous mixtures of a Biopharmaceutics classification system (BCS) class IV drug, furosemide (FUR). FUR mixtures with VER, PIP and QRT were prepared by solvent evaporation, and mixtures with ARG were prepared by spray drying in 1:1 and 1:2 molar ratios. The solid-state properties of the mixtures were characterized with X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) in stability studies under different storage conditions. Simultaneous dissolution/permeation studies were conducted in side-by-side diffusion cells with a PAMPA (parallel artificial membrane permeability assay) membrane as a permeation barrier. It was observed with XRPD that ARG, VER and PIP formed co-amorphous mixtures with FUR at both molar ratios. DSC and FTIR revealed single glass transition values for the mixtures (except for FUR:VER 1:2), with the formation of intermolecular interactions between the components, especially salt formation between FUR and ARG. The co-amorphous mixtures were found to be stable for at least two months under an elevated temperature/humidity, except FUR:ARG 1:2, which was sensitive to humidity. The dissolution/permeation studies showed that only the co-amorphous FUR:ARG mixtures were able to enhance both the dissolution and permeation of FUR. Thus, it is concluded that formulating co-amorphous salts with ARG may be a promising option for poorly soluble/permeable FUR.

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Effect of Poly(L-lysine) and Heparin Coatings on the Surface of Polyester-Based Particles on Prednisolone Release and Biocompatibility

Pharmaceutics ◽

10.3390/pharmaceutics13060801 ◽

2021 ◽

Vol 13 (6) ◽

pp. 801

Author(s):

Abdelrahman Mohamed ◽

Viktor Korzhikov-Vlakh ◽

Nan Zhang ◽

André Said ◽

Iuliia Pilipenko ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Molecular Diffusion ◽

Corneal Opacity ◽

Testing Strategy ◽

Release Process ◽

Irritation Test ◽

Model Drug ◽

Novel Drug ◽

Permeability Assay

A plethora of micro- and nanoparticle types are currently investigated for advanced ocular treatment due to improved drug retention times, higher bioavailability and better biocompatibility. Yet, comparative studies of both physicochemical and toxicological performance of these novel drug delivery systems are still rare. Herein, poly(L-lactic acid)- and poly(ε-caprolactone)-based micro- and nanoparticles were loaded with prednisolone as a model drug. The physicochemical properties of the particles were varied with respect to their hydrophilicity and size as well as their charge and the effect on prednisolone release was evaluated. The particle biocompatibility was assessed by a two-tier testing strategy, combining the EpiOcularTM eye irritation test and bovine corneal opacity and permeability assay. The biodegradable polyelectrolyte corona on the particles’ surface determined the surface charge and the release rate, enabling prednisolone release for at least 30 days. Thereby, the prednisolone release process was mainly governed by molecular diffusion. Finally, the developed particle formulations were found to be nontoxic in the tested range of concentrations.

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Parallel artificial membrane permeability assay for blood–brain permeability determination of illicit drugs and synthetic analogues

Science & Justice ◽

10.1016/j.scijus.2014.06.004 ◽

2014 ◽

Vol 54 (5) ◽

pp. 351-355 ◽

Cited By ~ 5

Author(s):

Kristina Clemons ◽

Amanda Kretsch ◽

Guido Verbeck

Keyword(s):

Membrane Permeability ◽

Illicit Drugs ◽

Artificial Membrane ◽

Synthetic Analogues ◽

Blood Brain ◽

Permeability Assay

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Metabolism of Selected 2-Arylbenzofurans in a Colon In Vitro Model System

Foods ◽

10.3390/foods10112754 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2754

Author(s):

Ondrej Vesely ◽

Petr Marsik ◽

Veronika Jarosova ◽

Ivo Doskocil ◽

Karel Smejkal ◽

...

Keyword(s):

In Vitro Model ◽

Biological Effects ◽

Bacterial Fermentation ◽

Basolateral Side ◽

Sufficient Stability ◽

Polar Metabolites ◽

Fermentation Model ◽

Vitro Model ◽

Permeability Assay

2-arylbenzofurans represent a small group of bioactive compounds found in the plant family Moraceae. As it has not been investigated whether these substances are stable during passage through the gastrointestinal tract, their biological effects may be altered by the metabolism of intestinal microbiota or cells. The aim of the present study was to investigate and compare mulberrofuran Y (1), moracin C (2), and mulberrofuran G (3) in an in vitro model of human intestinal bacterial fermentation and in an epithelial model using the Caco-2 cell line. The analysis of compounds by LC-MS-Q-TOF showed sufficient stability in the fermentation model, with no bacterial metabolites detected. However, great differences in the quantity of permeation were observed in the permeability assay. Moreover, mulberrofuran Y (1) and moracin C (2) were observed to be transformed into polar metabolites by conjugation. Among the test compounds, mulberrofuran Y (1) was mostly stable and accumulated in endothelial cells (85.3%) compared with mulberrofuran G (3) and moracin C (2) (14% and 8.2%, respectively). Thus, only a small amount of mulberrofuran Y (1) was conjugated. Moracin C (2) and mulberrofuran G (3) were metabolized almost completely, with only traces of the unchanged molecule being found on the apical and cellular sides of the system. Only conjugates of mulberrofuran Y (1) and moracin C (2) were able to reach the basolateral side. Our results provide the basic description of bioavailability of these three compounds, which is a necessary characteristic for final evaluation of bio-efficacy.

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