TY - JOUR

T1 - Influence of polymer addition on the amorphization, dissolution and physical stability of co-amorphous systems

AU - Liu, Jingwen

AU - Grohganz, Holger

AU - Rades, Thomas

PY - 2020

Y1 - 2020

N2 - Co-amorphous systems have been developed to address the solubility challenge of poorly-water soluble drugs. However, the dissolution rate of co-amorphous systems can be too fast in some cases, causing super-saturation, followed by precipitation and thereafter loss of the advantage. In this study, hydroxypropyl methylcellulose (HPMC) was co-formulated at 10% (w/w) with carvedilol-L-aspartic acid (CAR-ASP) co-amorphous systems at CAR to ASP molar ratios of 1:1, 1:1.5 and 1:2. No obvious changes of glass transition temperatures (T(g)s) were detected for CAR-ASP 1:1.5-HPMC and CAR-ASP 1:2-HPMC compared to the corresponding co-amorphous systems, whilst CAR-ASP 1:1-HPMC showed an increased T-g (88.9 +/- 1.3 degrees C) compared to CAR-ASP 1:1 (80.2 +/- 0.9 degrees C). HPMC was involved in the molecular interactions of the CAR-ASP-HPMC systems, but did not disturb ionic interactions between CAR and ASP. Addition of HPMC optimized the dissolution of the CAR-ASP systems by reducing the initial dissolution rate and maintaining super-saturation for a longer period. No negative effect of HPMC addition on physical stability was observed at 25 degrees C and 40 degrees C under dry conditions for 7 months. Therefore, it appears promising to co-formulate a small amount of polymer with co-amorphous systems to achieve optimized dissolution characteristics while maintaining the desired physical stability.

AB - Co-amorphous systems have been developed to address the solubility challenge of poorly-water soluble drugs. However, the dissolution rate of co-amorphous systems can be too fast in some cases, causing super-saturation, followed by precipitation and thereafter loss of the advantage. In this study, hydroxypropyl methylcellulose (HPMC) was co-formulated at 10% (w/w) with carvedilol-L-aspartic acid (CAR-ASP) co-amorphous systems at CAR to ASP molar ratios of 1:1, 1:1.5 and 1:2. No obvious changes of glass transition temperatures (T(g)s) were detected for CAR-ASP 1:1.5-HPMC and CAR-ASP 1:2-HPMC compared to the corresponding co-amorphous systems, whilst CAR-ASP 1:1-HPMC showed an increased T-g (88.9 +/- 1.3 degrees C) compared to CAR-ASP 1:1 (80.2 +/- 0.9 degrees C). HPMC was involved in the molecular interactions of the CAR-ASP-HPMC systems, but did not disturb ionic interactions between CAR and ASP. Addition of HPMC optimized the dissolution of the CAR-ASP systems by reducing the initial dissolution rate and maintaining super-saturation for a longer period. No negative effect of HPMC addition on physical stability was observed at 25 degrees C and 40 degrees C under dry conditions for 7 months. Therefore, it appears promising to co-formulate a small amount of polymer with co-amorphous systems to achieve optimized dissolution characteristics while maintaining the desired physical stability.

KW - Co-amorphous

KW - Polymer

KW - Amorphization

KW - Molecular interaction

KW - Dissolution

KW - Physical stability

KW - SOLID DISPERSIONS

KW - DRUG-DELIVERY

KW - AMINO-ACIDS

KW - IN-VITRO

KW - BEHAVIOR

KW - CRYSTALLIZATION

KW - STATE

KW - STABILIZATION

KW - FORMERS

U2 - 10.1016/j.ijpharm.2020.119768

DO - 10.1016/j.ijpharm.2020.119768

M3 - Journal article

C2 - 32798592

VL - 588

SP - 1

EP - 9

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

M1 - 119768

ER -