Impact of incorporated drugs on material properties of amorphous solid dispersions

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 159; pp. 88 - 98
• Main Authors: Flügel, Karsten, Schmidt, Katharina, Mareczek, Lena, Gäbe, Michael, Hennig, Robert, Thommes, Markus
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-02-2021
• Subjects: Amorphous solid dispersion; Hot-melt extrusion; Mechanical characterization; Nanoindentation; Tablet compression; Tablet disintegration; Wettability; Hot-melt extrusion; Amorphous solid dispersion; Wettability; Nanoindentation; Mechanical characterization; Tablet disintegration; Tablet compression
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2020.12.017

[Display omitted]
Formulation development of amorphous solid dispersions (ASD) still is challenging although several poorly water-soluble drugs have been marketed using this technique. During development of novel drugs, the selection of the preparation technique and polymer matrix is commonly performed for the certain drug via screening tools. However, if general trends regarding material properties are to be investigated, this approach is not beneficial, although often utilized in literature. The main component of the ASD usually is the polymer and thus it predominantly determines the material properties of the system. Therefore, to study the impact of different drugs and their drug loads on mechanical properties and wettability, three poorly soluble model drugs with drug loads ranging from 10% to 40% were incorporated into copovidone via hot-melt extrusion. The obtained extrudates were subsequently characterized regarding mechanical properties by applying diametral compression test and nanoindentation and the results were compared to the performance during tablet compression. Incorporation of all tested drugs resulted in a similar increase in brittleness of the ASDs, whereas the Young’s modulus and hardness changed differently in dependence of the incorporated drug. These observations correlated well with the performance during tablet compression and it was concluded, that the brittleness seemed to be the predominant factor influencing the compression behavior of copovidone-based ASDs. Furthermore, the degree of water absorption and wettability was assessed by applying dynamic vapor sorption experiments and contact angle measurements. Here, the incorporated drugs impacted the contact angle to different degrees and a strong correlation between the contact angle and disintegration time was observable. These results highlight the importance of thorough characterization of the ASDs as it helps to predict their performance during tablet compression and thus facilitates the optimal selection of excipients.