TY  - JOUR
AU  - Mitrović, Jelena
AU  - Divović-Matović, Branka
AU  - Knutson, Daniel
AU  - Đoković, Jelena
AU  - Kremenović, Aleksandar
AU  - Dobričić, Vladimir
AU  - Ranđelović, Danijela
AU  - Pantelić, Ivana
AU  - Cook, James
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3934
AB  - Poor water solubility of new chemical entities is considered as one of the main obstacles in drug development, as it usually leads to low bioavailability after administration. To overcome these problems, the selection of the appropriate formulation technology needs to be based on the physicochemical properties of the drug and introduced in the early stages of drug research. One example of the new potential drug substance with poor solubility is DK-I-60-3, deuterated pyrazoloquinolinone, designed for the treatment of various neuropsychiatric disorders. In this research, based on preformulation studies, nanocrystal technology was chosen to improve the oral bioavailability of DK-I-60-3. Nanocrystal dispersions stabilized by sodium lauryl sulfate and polyvinylpyrrolidone were prepared by modified wet media milling technique, with the selection of appropriate process and formulation parameters. The nanoparticles characterization included particle size and zeta potential measurements, differential scanning calorimetry, X-ray powder diffraction, dissolution and solubility study, and in vivo pharmacokinetic experiments. Developed formulations had small uniform particle sizes and were stable for three months. Nanonization caused decreased crystallite size and induced crystal defects formation, as well as a DK-I-60-3 solubility increase. Furthermore, after oral administration of the developed formulations in rats, two to three-fold bioavailability enhancement was observed in plasma and investigated organs, including the brain.
PB  - MDPI AG
T2  - Pharmaceutics
T1  - Overcoming the low oral bioavailability of deuterated pyrazoloquinolinone ligand dk-i-60-3 by nanonization: A knowledge-based approach
VL  - 13
IS  - 8
DO  - 10.3390/pharmaceutics13081188
ER  - 

@article{
author = "Mitrović, Jelena and Divović-Matović, Branka and Knutson, Daniel and Đoković, Jelena and Kremenović, Aleksandar and Dobričić, Vladimir and Ranđelović, Danijela and Pantelić, Ivana and Cook, James and Savić, Miroslav and Savić, Snežana",
year = "2021",
abstract = "Poor water solubility of new chemical entities is considered as one of the main obstacles in drug development, as it usually leads to low bioavailability after administration. To overcome these problems, the selection of the appropriate formulation technology needs to be based on the physicochemical properties of the drug and introduced in the early stages of drug research. One example of the new potential drug substance with poor solubility is DK-I-60-3, deuterated pyrazoloquinolinone, designed for the treatment of various neuropsychiatric disorders. In this research, based on preformulation studies, nanocrystal technology was chosen to improve the oral bioavailability of DK-I-60-3. Nanocrystal dispersions stabilized by sodium lauryl sulfate and polyvinylpyrrolidone were prepared by modified wet media milling technique, with the selection of appropriate process and formulation parameters. The nanoparticles characterization included particle size and zeta potential measurements, differential scanning calorimetry, X-ray powder diffraction, dissolution and solubility study, and in vivo pharmacokinetic experiments. Developed formulations had small uniform particle sizes and were stable for three months. Nanonization caused decreased crystallite size and induced crystal defects formation, as well as a DK-I-60-3 solubility increase. Furthermore, after oral administration of the developed formulations in rats, two to three-fold bioavailability enhancement was observed in plasma and investigated organs, including the brain.",
publisher = "MDPI AG",
journal = "Pharmaceutics",
title = "Overcoming the low oral bioavailability of deuterated pyrazoloquinolinone ligand dk-i-60-3 by nanonization: A knowledge-based approach",
volume = "13",
number = "8",
doi = "10.3390/pharmaceutics13081188"
}

Mitrović, J., Divović-Matović, B., Knutson, D., Đoković, J., Kremenović, A., Dobričić, V., Ranđelović, D., Pantelić, I., Cook, J., Savić, M.,& Savić, S.. (2021). Overcoming the low oral bioavailability of deuterated pyrazoloquinolinone ligand dk-i-60-3 by nanonization: A knowledge-based approach. in Pharmaceutics
MDPI AG., 13(8).
https://doi.org/10.3390/pharmaceutics13081188

Mitrović J, Divović-Matović B, Knutson D, Đoković J, Kremenović A, Dobričić V, Ranđelović D, Pantelić I, Cook J, Savić M, Savić S. Overcoming the low oral bioavailability of deuterated pyrazoloquinolinone ligand dk-i-60-3 by nanonization: A knowledge-based approach. in Pharmaceutics. 2021;13(8).
doi:10.3390/pharmaceutics13081188 .

Mitrović, Jelena, Divović-Matović, Branka, Knutson, Daniel, Đoković, Jelena, Kremenović, Aleksandar, Dobričić, Vladimir, Ranđelović, Danijela, Pantelić, Ivana, Cook, James, Savić, Miroslav, Savić, Snežana, "Overcoming the low oral bioavailability of deuterated pyrazoloquinolinone ligand dk-i-60-3 by nanonization: A knowledge-based approach" in Pharmaceutics, 13, no. 8 (2021),
https://doi.org/10.3390/pharmaceutics13081188 . .