Compaction Behavior of Co-Amorphous Systems

Co-amorphous systems have been shown to be a promising strategy to address the poor water solubility of many drug candidates. However, little is known about the effect of downstream processing-induced stress on these systems. The aim of this study is to investigate the compaction properties of co-amorphous materials and their solid-state stability upon compaction. Model systems of co-amorphous materials consisting of carvedilol and the two co-formers aspartic acid and tryptophan were produced via spray drying. The solid state of matter was characterized using XRPD, DSC, and SEM.

Co-amorphous tablets were produced with a compaction simulator, using varying amounts of MCC in the range of 24 to 95.5% (w/w) as a filler, and showed high compressibility. Higher contents of co-amorphous material led to an increase in the disintegration time; however, the tensile strength remained rather constant at around 3.8 MPa. No indication of recrystallization of the co-amorphous systems was observed. This study found that co-amorphous systems are able to deform plastically under pressure and form mechanically stable tablets.

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Materials

Carvedilol polymorphic form II (CAR, M=406.47 g/mol, code GIVJUQ01) was obtained from Hovione FarmaCiencia (Loures, Portugal) (GIVJUQ01). Carvedilol exhibits pH-dependent solubility with a pKa of 7.8 and is practically insoluble at pH values higher than 9.0. The solubility of carvedilol is around 23 μg/mL at a pH of 7. The glass transition temperature of amorphous CAR was reported at around 40 °C [25]. L-aspartic acid (ASP, M=133.11 g/mol) was purchased from Calbiochem-novabiochem AG (Darmstadt, Germany), L-tryptophan (TRP, M=204.23 g/mol) was purchased from Sigma Aldrich (St. Louis, MO, USA), and microcrystalline cellulose, grade Avicel 102, (MCC, M=370.35 g/mol) was purchased from Fagron Services B.V. (DB Uitgeest, The Netherlands). All substances were of reagent grade. Ethanol of 96% and demineralized water were used as solvents.

Sørensen, C.-M.; Rantanen, J.; Grohganz, H. Compaction Behavior of Co-Amorphous Systems. Pharmaceutics 2023, 15, 858. https://doi.org/10.3390/pharmaceutics15030858