Collected Item: “Overcoming the Low Oral Bioavailability of Deuterated Pyrazoloquinolinone Ligand DK-I-60-3 by Nanonization: A Knowledge-Based Approach”
Врста публикације
Рад у часопису
Верзија рада
објављена верзија
Језик рада
енглески
Аутор/и (Милан Марковић, Никола Николић)
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 and Snežana D. Savić
Наслов рада (Наслов - поднаслов)
Overcoming the Low Oral Bioavailability of Deuterated Pyrazoloquinolinone Ligand DK-I-60-3 by Nanonization: A Knowledge-Based Approach
Наслов часописа
Pharmaceutics
Издавач (Београд : Просвета)
MDPI, Basel, Switzerland
Година издавања
2021
Сажетак на енглеском језику
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.
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 часописа
13
Почетна страна
1188
Укупан број страна рада (уколико не постоји пагинација)
19
DOI број
10.3390/pharmaceutics13081188
ISSN број часописа
1999-4923
Кључне речи на српском (одвојене знаком ", ")
pyrazoloquinolinones, nanocrystals, wet media milling, fasted/fed bioavailability
Кључне речи на енглеском (одвојене знаком ", ")
pyrazoloquinolinones, nanocrystals, wet media milling, fasted/fed bioavailability
Линк
https://www.mdpi.com/1999-4923/13/8/1188
Шира категорија рада према правилнику МПНТ
M20
Ужа категорија рада према правилнику МПНТ
М21
Степен доступности
Отворени приступ
Лиценца
Creative Commons – Attribution 4.0 International
Формат дигиталног објекта
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