Ball milling and hot-melt extrusion of indomethacin-L-arginine-vinylpyrrolidone-vinyl acetate copolymer: Solid-state properties and dissolution performance

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F22%3A43924989" target="_blank" >RIV/60461373:22310/22:43924989 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22340/22:43924989

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0378517321012308?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0378517321012308?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ijpharm.2021.121424" target="_blank" >10.1016/j.ijpharm.2021.121424</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Ball milling and hot-melt extrusion of indomethacin-L-arginine-vinylpyrrolidone-vinyl acetate copolymer: Solid-state properties and dissolution performance

Popis výsledku v původním jazyce

Commonly applied approaches to enhance the dissolution properties of low water-soluble crystalline active pharmaceutical ingredients (APIs) include their amorphization by incorporation into a polymeric matrix and the formation of amorphous solid dispersions, or blending APIs with low-molecular-weight excipients and the formation of a co-amorphous system. This study focused on the preparation and characterization of binary (consisting of indomethacin (IND) and polymer - copovidone (PVP VA 64), as a carrier, or amino acid - L-arginine (ARG), as a co-former) and ternary (comprising the same API, polymer, and amino acid) formulations. Formulations were produced by ball milling (BM) and/or hot-melt extrusion (HME), and extensive physicochemical characterization was performed. Specifically, the physicochemical and solid-state properties of a model IND-ARG system incorporated into a polymeric matrix of PVP VA 64 by HME and BM as well as by combined BM/HME method together with the impact of the preparation strategy on the dissolution profiles and long-term physical stability were investigated. Ball-milled binary and ternary formulations were found to be amorphous. The residual crystals corresponding to IND-ARG salt were identified in the ternary formulations produced via HME. Despite the presence of a crystalline phase, dissolution tests showed that ternary systems prepared by HME exhibited improved IND solubility when compared to pure crystalline IND and their corresponding physical mixture. None of the binary and ternary formulations that were initially fully amorphous did undergo recrystallization during the entire period of preservation (minimum of 12 months) in dry conditions at 25 degrees C.

Název v anglickém jazyce

Ball milling and hot-melt extrusion of indomethacin-L-arginine-vinylpyrrolidone-vinyl acetate copolymer: Solid-state properties and dissolution performance

Popis výsledku anglicky

Commonly applied approaches to enhance the dissolution properties of low water-soluble crystalline active pharmaceutical ingredients (APIs) include their amorphization by incorporation into a polymeric matrix and the formation of amorphous solid dispersions, or blending APIs with low-molecular-weight excipients and the formation of a co-amorphous system. This study focused on the preparation and characterization of binary (consisting of indomethacin (IND) and polymer - copovidone (PVP VA 64), as a carrier, or amino acid - L-arginine (ARG), as a co-former) and ternary (comprising the same API, polymer, and amino acid) formulations. Formulations were produced by ball milling (BM) and/or hot-melt extrusion (HME), and extensive physicochemical characterization was performed. Specifically, the physicochemical and solid-state properties of a model IND-ARG system incorporated into a polymeric matrix of PVP VA 64 by HME and BM as well as by combined BM/HME method together with the impact of the preparation strategy on the dissolution profiles and long-term physical stability were investigated. Ball-milled binary and ternary formulations were found to be amorphous. The residual crystals corresponding to IND-ARG salt were identified in the ternary formulations produced via HME. Despite the presence of a crystalline phase, dissolution tests showed that ternary systems prepared by HME exhibited improved IND solubility when compared to pure crystalline IND and their corresponding physical mixture. None of the binary and ternary formulations that were initially fully amorphous did undergo recrystallization during the entire period of preservation (minimum of 12 months) in dry conditions at 25 degrees C.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

<a href="/cs/project/GA19-02889S" target="_blank" >GA19-02889S: Stabilita amorfních pevných disperzí: Predikce pomocí stavových rovnic SAFT a jejich experimentální ověření</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

International Journal of Pharmaceutics

ISSN

0378-5173

e-ISSN

1873-3476

Svazek periodika

613

Číslo periodika v rámci svazku

únor 2022

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

121424

Kód UT WoS článku

000742653100007

EID výsledku v databázi Scopus

2-s2.0-85122227362