Scale-up from batch to flow-through wet milling process for injectable depot formulation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F16%3A43902086" target="_blank" >RIV/60461373:22340/16:43902086 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.ejps.2016.08.043" target="_blank" >http://dx.doi.org/10.1016/j.ejps.2016.08.043</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejps.2016.08.043" target="_blank" >10.1016/j.ejps.2016.08.043</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Scale-up from batch to flow-through wet milling process for injectable depot formulation

Popis výsledku v původním jazyce

Injectable depot formulations are aimed at providing long-term sustained release of a drug into systemic circulation, thus reducing plasma level fluctuations and improving patient compliance. The particle size distribution of the formulation in the form of suspension is a key parameter that controls the release rate. In this work, the process of wet stirred media milling (ball milling) of a poorly water-soluble substance has been investigated with two main aims: (i) to determine the parametric sensitivity of milling kinetics; and (ii) to develop scale-up methodology for process transfer from batch to flow-through arrangement. Ball milling experiments were performed in two types of ball mills, a batch mill with a 30 ml maximum working volume, and a flow-through mill with a 250 ml maximum working volume. Milling parameters were investigated in detail by methodologies of QbD to map the parametric space. Specifically, the effects of ball size, ball fill level, and rpm on the particle breakage kinetics were systematically investigated at both mills, with an additional parameter (flow-rate) in the case of the flow-through mill. The breakage rate was found to follow power-law kinetics with respect to dimensionless time, with an asymptotic d50 particle size in the range of 200?300 nm. In the case of the flow-through mill, the number of theoretical passes through the mill was found to be an important scale-up parameter. ? 2016 Elsevier B.V.

Název v anglickém jazyce

Scale-up from batch to flow-through wet milling process for injectable depot formulation

Popis výsledku anglicky

Injectable depot formulations are aimed at providing long-term sustained release of a drug into systemic circulation, thus reducing plasma level fluctuations and improving patient compliance. The particle size distribution of the formulation in the form of suspension is a key parameter that controls the release rate. In this work, the process of wet stirred media milling (ball milling) of a poorly water-soluble substance has been investigated with two main aims: (i) to determine the parametric sensitivity of milling kinetics; and (ii) to develop scale-up methodology for process transfer from batch to flow-through arrangement. Ball milling experiments were performed in two types of ball mills, a batch mill with a 30 ml maximum working volume, and a flow-through mill with a 250 ml maximum working volume. Milling parameters were investigated in detail by methodologies of QbD to map the parametric space. Specifically, the effects of ball size, ball fill level, and rpm on the particle breakage kinetics were systematically investigated at both mills, with an additional parameter (flow-rate) in the case of the flow-through mill. The breakage rate was found to follow power-law kinetics with respect to dimensionless time, with an asymptotic d50 particle size in the range of 200?300 nm. In the case of the flow-through mill, the number of theoretical passes through the mill was found to be an important scale-up parameter. ? 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/GA15-05534S" target="_blank" >GA15-05534S: Studie vztahu mezi strukturou a vlastnostmi složitých granulárních systémů a dynamiky jejich lámání</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

8

Strana od-do

122-129

Kód UT WoS článku

000390505100015

EID výsledku v databázi Scopus

2-s2.0-84995389744