In vitro pH dependent passive transport of ketoprofen and metformin

Elezovic, A; Marić, Amina; Biščević, Amila; Hadžiabdić, Jasmina; Škrbo, Selma; Špirtović-Halilović, Selma; Rahić, Ognjenka; Vranić, Edina

doi:10.5599/admet.916

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…This level of lipophilicity, however, was still not enough to exert measurable permeability. For approved drugs with similar structural characteristics (e.g., camostat, melagatran, xylometazoline, metformin), only very limited permeabilities are described as well [50][51][52][53]. All this indicates the pronounced hindering effect of the guanidine group for passive permeation.…”

Section: Parallel Artificial Membrane Permeation Assay (Pampa)mentioning

confidence: 99%

Ligand-Based Design of Selective Peptidomimetic uPA and TMPRSS2 Inhibitors with Arg Bioisosteres

Müller,

Zimmer,

Frey

et al. 2024

IJMS

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Trypsin-like serine proteases are involved in many important physiological processes like blood coagulation and remodeling of the extracellular matrix. On the other hand, they are also associated with pathological conditions. The urokinase-pwlasminogen activator (uPA), which is involved in tissue remodeling, can increase the metastatic behavior of various cancer types when overexpressed and dysregulated. Another member of this protease class that received attention during the SARS-CoV 2 pandemic is TMPRSS2. It is a transmembrane serine protease, which enables cell entry of the coronavirus by processing its spike protein. A variety of different inhibitors have been published against both proteases. However, the selectivity over other trypsin-like serine proteases remains a major challenge. In the current study, we replaced the arginine moiety at the P1 site of peptidomimetic inhibitors with different bioisosteres. Enzyme inhibition studies revealed that the phenylguanidine moiety in the P1 site led to strong affinity for TMPRSS2, whereas the cyclohexylguanidine derivate potently inhibited uPA. Both inhibitors exhibited high selectivity over other structurally similar and physiologically important proteases.

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Section: Parallel Artificial Membrane Permeation Assay (Pampa)mentioning

confidence: 99%

Ligand-Based Design of Selective Peptidomimetic uPA and TMPRSS2 Inhibitors with Arg Bioisosteres

Müller,

Zimmer,

Frey

et al. 2024

IJMS

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show abstract

“…However, the jejunum and the colon are also important sites of absorption, where the absorption is pH-dependent as pH 6.5 resulted in higher plasma levels of ketoprofen compared to 7.4 in both anatomical locations [ 11 ]. The apparent permeation coefficient is also pH dependent, having a maximum at the p K a value of the molecule, which is pH 4.45 [ 12 ]. As a widely used and easy to detect model API, multiple publications can be found about the enhanced oral delivery of ketoprofen, in form of liquid self-nanoemulsifying drug delivery systems, nanoscale milled powders, or salification [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Molecular Weight on the Dissolution Profiles of PEG Solid Dispersions Containing Ketoprofen

et al. 2023

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Solid dispersions are typically binary systems with a hydrophilic matrix polymer and a lipophilic active substance. During formulation, the drug undergoes a crystalline to amorphous phase transition, which leads to a supersaturated solution providing enhanced bioavailability. The interaction of the active substance and the polymer is unique and influences the level of supersaturation. We aimed to investigate the relationship between low molecular weight polyethylene glycol derivates PEG 1000, 1500, and 2000 and ketoprofen regarding the effect of molecular weight. The physicochemical properties of solid dispersions prepared with hot melt homogenization and their respective physical mixtures were investigated with Fourier transform infrared spectroscopy, powder X-ray diffraction and scanning electron microscopy techniques. A phase solubility study was carried out in hydrochloric acid media which showed no difference between the three polymers, but the dissolution curves differed considerably. PEG 1000 had higher percentage of released drug than PEG 1500 and 2000, which had similar results. These results indicate that when multiple low molecular weight PEGs are suitable as matrix polymers of solid dispersions, the molecular weight has only limited impact on physicochemical characteristics and interactions and further investigation is needed to select the most applicable candidate.

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One‐Pot Synthesis of Sustainable Fluorescent Nanomaterials via Microwave Irradiation as a Probe for the Determination of Metformin in Pure and Pharmaceutical Dosage Forms: Greenness and Whiteness Metrics

Abou El‐Alamin,

Mohamed,

Farag

2024

Luminescence

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A rapid, green and sensitive technique for the determination of metformin determination was developed based on the direct fluorescence enhancement of carbon dots (CDs) induced by the cited drug. The water‐soluble CDs were prepared via a one‐pot synthesis from avocado peels using domestic microwave. The prepared CDs exhibited strong fluorescence at 405 nm after excitation at 320 nm with a quantum yield of 51%. The fluorescence of CDs was enhanced linearly by increasing the concentration of metformin within the range 0.5–25 μg/mL with limit of detection 0.087 μg/mL and limit of quantification 0.263 μg/mL. The designed probe was proved to be selective toward metformin in the presence of other drugs such as vildagliptin and alogliptin and also in the presence of excipients in the pharmaceutical dosage form. The suggested and reported methods were compared with the help of the whiteness and greenness tools, specifically the white analytical chemistry and analytical greenness metric tools, for assessing hazardous solvents and reagents used.

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In vitro pH dependent passive transport of ketoprofen and metformin

Cited by 4 publications

References 26 publications

Ligand-Based Design of Selective Peptidomimetic uPA and TMPRSS2 Inhibitors with Arg Bioisosteres

Ligand-Based Design of Selective Peptidomimetic uPA and TMPRSS2 Inhibitors with Arg Bioisosteres

Effect of Molecular Weight on the Dissolution Profiles of PEG Solid Dispersions Containing Ketoprofen

One‐Pot Synthesis of Sustainable Fluorescent Nanomaterials via Microwave Irradiation as a Probe for the Determination of Metformin in Pure and Pharmaceutical Dosage Forms: Greenness and Whiteness Metrics

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