Transformations between Co-Amorphous and Co-Crystal Systems and Their Influence on the Formation and Physical Stability of Co-Amorphous Systems

TY - JOUR

T1 - Transformations between Co-Amorphous and Co-Crystal Systems and Their Influence on the Formation and Physical Stability of Co-Amorphous Systems

AU - Wu, Wenqi

AU - Wang, Yixuan

AU - Löbmann, Korbinian

AU - Grohganz, Holger

AU - Rades, Thomas

PY - 2019/3/4

Y1 - 2019/3/4

N2 - The formation of co-amorphous and co-crystal systems are attractive formulation strategies for poorly water-soluble drugs. Intermolecular interactions between the drug and the coformer(s) play an important role in the formation of both systems, making the investigation of transformations between the two systems specifically interesting. The aim of this study thus was to investigate the transformation between the two systems and its influence on the formation and physical stability of co-amorphous systems. Carbamazepine (CBZ) along with benzoic acid, maleic acid, succinic acid, tartaric acid, saccharin, and nicotinamide were used as materials. First, CBZ-co-former co-crystals were prepared. Then the co-crystals and CBZ-co-former physical mixtures were ball milled to investigate the possible co-amorphization process. The XRPD and DSC results showed that CBZ and coformers tended to maintain (co-crystals as the starting material) or form co-crystals (physical mixtures as the starting material), rather than to form co-amorphous systems. Next, co-amorphization from CBZ-co-former physical mixtures via quench cooling was studied. While co-amorphous systems were obtained, the physical stability of these was very low, and the samples recrystallized to either co-crystal forms or the individual components. In conclusion, a possible transformation between the two systems was confirmed, but the resulting co-amorphous systems were highly unstable.

AB - The formation of co-amorphous and co-crystal systems are attractive formulation strategies for poorly water-soluble drugs. Intermolecular interactions between the drug and the coformer(s) play an important role in the formation of both systems, making the investigation of transformations between the two systems specifically interesting. The aim of this study thus was to investigate the transformation between the two systems and its influence on the formation and physical stability of co-amorphous systems. Carbamazepine (CBZ) along with benzoic acid, maleic acid, succinic acid, tartaric acid, saccharin, and nicotinamide were used as materials. First, CBZ-co-former co-crystals were prepared. Then the co-crystals and CBZ-co-former physical mixtures were ball milled to investigate the possible co-amorphization process. The XRPD and DSC results showed that CBZ and coformers tended to maintain (co-crystals as the starting material) or form co-crystals (physical mixtures as the starting material), rather than to form co-amorphous systems. Next, co-amorphization from CBZ-co-former physical mixtures via quench cooling was studied. While co-amorphous systems were obtained, the physical stability of these was very low, and the samples recrystallized to either co-crystal forms or the individual components. In conclusion, a possible transformation between the two systems was confirmed, but the resulting co-amorphous systems were highly unstable.

KW - co-amorphous systems

KW - co-crystal systems

KW - physical stability

KW - recrystallization

KW - transformation

UR - http://www.scopus.com/inward/record.url?scp=85060803080&partnerID=8YFLogxK

U2 - 10.1021/acs.molpharmaceut.8b01229

DO - 10.1021/acs.molpharmaceut.8b01229

M3 - Journal article

C2 - 30624075

AN - SCOPUS:85060803080

SN - 1543-8384

VL - 16

SP - 1294

EP - 1304

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

IS - 3

ER -