Overcoming the Low Oral Bioavailability of Deuterated Pyrazoloquinolinone Ligand DK-I-60-3 by Nanonization: A Knowledge-Based Approach

Објеката

Тип
Рад у часопису
Верзија рада
објављена верзија
Језик
енглески
Креатор
Jelena R. Mitrović , Branka Divović-Matović, Daniel E. Knutson, Jelena B. Ðoković, Aleksandar Kremenović, Vladimir D. Dobričić, Danijela V. Randjelović, Ivana Pantelić, James M. Cook, Miroslav M. Savić, Snežana D. Savić
Извор
Pharmaceutics
Издавач
MDPI, Basel, Switzerland
Датум издавања
2021
Сажетак
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.
Број
13
почетак странице
1188
број страница
19
doi
10.3390/pharmaceutics13081188
issn
1999-4923
Subject
pyrazoloquinolinones, nanocrystals, wet media milling, fasted/fed bioavailability
Шира категорија рада
M20
Ужа категорија рада
М21
Права
Отворени приступ
Лиценца
Creative Commons – Attribution 4.0 International
Формат
.pdf

Jelena R. Mitrović , Branka Divović-Matović, Daniel E. Knutson, Jelena B. Ðoković, Aleksandar Kremenović, Vladimir D. Dobričić, Danijela V. Randjelović, Ivana Pantelić, James M. Cook, Miroslav M. Savić, Snežana D. Savić. "Overcoming the Low Oral Bioavailability of Deuterated Pyrazoloquinolinone Ligand DK-I-60-3 by Nanonization: A Knowledge-Based Approach" in Pharmaceutics, MDPI, Basel, Switzerland (2021). https://doi.org/10.3390/pharmaceutics13081188

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