The impact of polymeric excipients on the particle size of poorly soluble drugs after pH-induced precipitation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F16%3A43902088" target="_blank" >RIV/60461373:22340/16:43902088 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.ejps.2016.08.028" target="_blank" >http://dx.doi.org/10.1016/j.ejps.2016.08.028</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejps.2016.08.028" target="_blank" >10.1016/j.ejps.2016.08.028</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The impact of polymeric excipients on the particle size of poorly soluble drugs after pH-induced precipitation

Popis výsledku v původním jazyce

Active pharmaceutical ingredients (APIs) with strongly pH-dependent aqueous solubility can face the problem of precipitating from solution when the pH changes from acidic in the stomach to neutral in the intestine. The present work investigates the effect of two polymeric excipients ? polyvinylpyrrolidone (PVP) and Soluplus ? on the ability to either prevent precipitation, or to control the size distribution of precipitated particles when precipitation cannot be prevented. Two different APIs were compared, Dabigatran etexilate mesylate and Rilpivirine hydrochloride. The effect of excipient concentration on the precipitation behaviour during pH titration was systematically investigated and qualitatively different trends were observed: in case of Soluplus, which forms a micellar solution when critical micelle concentration is exceeded, precipitation was inhibited in the case of Dabigatran etexilate, which partitioned into the micelles. On the other hand, Rilpivirine precipitated independently of Soluplus concentration. In the case of PVP, which does not form micelles, precipitation could not be avoided. Increased polymer concentration, however prevented the aggregation of precipitated particles into larger cluster. The observed effect of PVP was especially pronounced for Rilpivirine. The main conclusion of this study is that a suitably chosen polymeric excipient can either prevent precipitation altogether or reduce the size of the resulting particles. The mechanism of action, however, seems-specific to a given molecule. It was also shown that the polymer-stabilised particles have a potential to redissolve. ? 2016 Elsevier B.V.

Název v anglickém jazyce

The impact of polymeric excipients on the particle size of poorly soluble drugs after pH-induced precipitation

Popis výsledku anglicky

Active pharmaceutical ingredients (APIs) with strongly pH-dependent aqueous solubility can face the problem of precipitating from solution when the pH changes from acidic in the stomach to neutral in the intestine. The present work investigates the effect of two polymeric excipients ? polyvinylpyrrolidone (PVP) and Soluplus ? on the ability to either prevent precipitation, or to control the size distribution of precipitated particles when precipitation cannot be prevented. Two different APIs were compared, Dabigatran etexilate mesylate and Rilpivirine hydrochloride. The effect of excipient concentration on the precipitation behaviour during pH titration was systematically investigated and qualitatively different trends were observed: in case of Soluplus, which forms a micellar solution when critical micelle concentration is exceeded, precipitation was inhibited in the case of Dabigatran etexilate, which partitioned into the micelles. On the other hand, Rilpivirine precipitated independently of Soluplus concentration. In the case of PVP, which does not form micelles, precipitation could not be avoided. Increased polymer concentration, however prevented the aggregation of precipitated particles into larger cluster. The observed effect of PVP was especially pronounced for Rilpivirine. The main conclusion of this study is that a suitably chosen polymeric excipient can either prevent precipitation altogether or reduce the size of the resulting particles. The mechanism of action, however, seems-specific to a given molecule. It was also shown that the polymer-stabilised particles have a potential to redissolve. ? 2016 Elsevier B.V.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CI - Průmyslová chemie a chemické inženýrství

OECD FORD obor

—

Projekt

<a href="/cs/project/GA13-37055S" target="_blank" >GA13-37055S: Dalkové ovládání adheze a reakčně-difuzních procesů ve strukturovaných mikročásticích</a><br>

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

European Journal of Pharmaceutical Sciences

ISSN

0928-0987

e-ISSN

—

Svazek periodika

95

Číslo periodika v rámci svazku

December 2016

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

138-144

Kód UT WoS článku

000390505100017

EID výsledku v databázi Scopus

2-s2.0-84994246973