Influence of Glass Forming Ability on the Physical Stability of Supersaturated Amorphous Solid Dispersions

TY - JOUR

T1 - Influence of Glass Forming Ability on the Physical Stability of Supersaturated Amorphous Solid Dispersions

AU - Blaabjerg, Lasse Ingerslev

AU - Bulduk, Bulut

AU - Lindenberg, Eleanor

AU - Löbmann, Korbinian

AU - Rades, Thomas

AU - Grohganz, Holger

PY - 2019/8

Y1 - 2019/8

N2 - In this study, the influence of the glass-forming ability (GFA) of a drug on its physical stability in a supersaturated solid dispersion was investigated. Nine drugs were classified according to their GFA using their respective critical cooling rate. Their respective solubility in poly(vinylpyrrolidone-co-vinyl acetate) 6:4 (PVPVA64) was predicted using the melting point depression method based on the Flory-Huggins lattice theory. Supersaturated amorphous solid dispersions at a level of 25% w/w drug above saturation solubility in the polymer were prepared by film-casting, and their respective physical stability at temperatures of 10°C or 20°C above or below their respective T g (dry conditions) was monitored by the use of polarized light microscopy. This study showed that drugs with good GFA (class 3) on average have higher physical stability in supersaturated amorphous solid dispersion compared to drug with modest GFA (class 2), which in turn have higher physical stability in supersaturated amorphous solid dispersion than drugs with poor GFA (class 1). These results indicate that the GFA of a drug and its physical stability in a supersaturated amorphous solid dispersion stored at a temperature above or below its T g are correlated.

AB - In this study, the influence of the glass-forming ability (GFA) of a drug on its physical stability in a supersaturated solid dispersion was investigated. Nine drugs were classified according to their GFA using their respective critical cooling rate. Their respective solubility in poly(vinylpyrrolidone-co-vinyl acetate) 6:4 (PVPVA64) was predicted using the melting point depression method based on the Flory-Huggins lattice theory. Supersaturated amorphous solid dispersions at a level of 25% w/w drug above saturation solubility in the polymer were prepared by film-casting, and their respective physical stability at temperatures of 10°C or 20°C above or below their respective T g (dry conditions) was monitored by the use of polarized light microscopy. This study showed that drugs with good GFA (class 3) on average have higher physical stability in supersaturated amorphous solid dispersion compared to drug with modest GFA (class 2), which in turn have higher physical stability in supersaturated amorphous solid dispersion than drugs with poor GFA (class 1). These results indicate that the GFA of a drug and its physical stability in a supersaturated amorphous solid dispersion stored at a temperature above or below its T g are correlated.

KW - amorphous

KW - crystallization

KW - formulation

KW - glass

KW - physical stability

KW - solid dispersion

KW - solid state

KW - solubility

UR - http://www.scopus.com/inward/record.url?scp=85063762169&partnerID=8YFLogxK

U2 - 10.1016/j.xphs.2019.02.028

DO - 10.1016/j.xphs.2019.02.028

M3 - Journal article

C2 - 30878513

AN - SCOPUS:85063762169

SN - 0022-3549

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

ER -