Long-term enzymatic dissolution method for poor water-soluble pharmaceutical formulation

Kód výsledku v IS VaVaI

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Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Long-term enzymatic dissolution method for poor water-soluble pharmaceutical formulation

Popis výsledku v původním jazyce

Sustained release (SR) injectable suspensions are already used in clinical practice because they have many advantages: lower frequency of administration, blood levels remain within therapeutic range, greater effectiveness and reduced side effects, as well as improved patient compliance. Such suspensions may be administered in the form of a low soluble drug, but the release time of such medication is dependent on the particle size and the specific surface area. In drug development, it is very important to have reliable method how to evaluate drug dissolution profile in in vitro conditions before clinical trials on animals and humans. In the case of low soluble drug, common dissolution tests are not applicable because of drug insolubility. Therefore, we have developed a new in vitro dissolution method to evaluate the dissolution profile of such medication. Moreover, this method is also useful for the development of generic drugs, to compare their dissolution profile to those of the reference. Enzymatic dissolution tests of our drug suspensions were conducted with various PSD by the enzyme serine esterase. We prepared those suspensions of various PSD by wet nano milling in a ball mill containing ZrO2 beads, based on previous parametric study where we investigated the impact of variable process parameters such as time, ball diameter, fill level and agitation rate. For each sample taken at various time intervals, the increase of API concentration and reduction of PSD of the suspension were evaluated using HPLC and laser diffraction, respectively. Based on the results of this work, the rate of kinetic release was found to correlate directly with an increase in the specific surface area of the particles in the suspensions. The proposed in vitro method is used to predict the pharmacokinetics of the medication under in vivo conditions. Thus, it can serve as a cheaper and faster alternative for bioequivalence studies (BES) on animals used in generic drug development. However, further validation studies will be required to relate our method quantitatively to real in vivo conditions.

Název v anglickém jazyce

Long-term enzymatic dissolution method for poor water-soluble pharmaceutical formulation

Popis výsledku anglicky

Sustained release (SR) injectable suspensions are already used in clinical practice because they have many advantages: lower frequency of administration, blood levels remain within therapeutic range, greater effectiveness and reduced side effects, as well as improved patient compliance. Such suspensions may be administered in the form of a low soluble drug, but the release time of such medication is dependent on the particle size and the specific surface area. In drug development, it is very important to have reliable method how to evaluate drug dissolution profile in in vitro conditions before clinical trials on animals and humans. In the case of low soluble drug, common dissolution tests are not applicable because of drug insolubility. Therefore, we have developed a new in vitro dissolution method to evaluate the dissolution profile of such medication. Moreover, this method is also useful for the development of generic drugs, to compare their dissolution profile to those of the reference. Enzymatic dissolution tests of our drug suspensions were conducted with various PSD by the enzyme serine esterase. We prepared those suspensions of various PSD by wet nano milling in a ball mill containing ZrO2 beads, based on previous parametric study where we investigated the impact of variable process parameters such as time, ball diameter, fill level and agitation rate. For each sample taken at various time intervals, the increase of API concentration and reduction of PSD of the suspension were evaluated using HPLC and laser diffraction, respectively. Based on the results of this work, the rate of kinetic release was found to correlate directly with an increase in the specific surface area of the particles in the suspensions. The proposed in vitro method is used to predict the pharmacokinetics of the medication under in vivo conditions. Thus, it can serve as a cheaper and faster alternative for bioequivalence studies (BES) on animals used in generic drug development. However, further validation studies will be required to relate our method quantitatively to real in vivo conditions.

Druh

D - Stať ve sborníku

CEP obor

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OECD FORD obor

20401 - Chemical engineering (plants, products)

Projekt

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Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název statě ve sborníku

PROCEEDINGS 44th International Conference of the Slovak Society of Chemical Engineering

ISBN

978-80-89597-58-1

ISSN

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e-ISSN

neuvedeno

Počet stran výsledku

1

Strana od-do

638

Název nakladatele

Slovak Society of Chemical Engineering

Místo vydání

Bratislava

Místo konání akce

Demänovská dolina

Datum konání akce

22. 5. 2017

Typ akce podle státní příslušnosti

WRD - Celosvětová akce

Kód UT WoS článku

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