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Eur J Pharm Biopharm. 2015 Oct;96:44-52. doi: 10.1016/j.ejpb.2015.07.011. Epub 2015 Jul 18.

Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine.

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Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Department of Pharmacy, University of Copenhagen, Denmark.
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany. Electronic address:


Co-amorphous drug formulations provide the possibility to stabilize a drug in its amorphous form by interactions with low molecular weight compounds, e.g. amino acids. Recent studies have shown the feasibility of spray drying as a technique to manufacture co-amorphous indomethacin-arginine in a larger production scale. In this work, a tablet formulation was developed for a co-amorphous salt, namely spray dried indomethacin-arginine (SD IND-ARG). The effects of compaction pressure on tablet properties, physical stability and dissolution profiles under non-sink conditions were examined. Dissolution profiles of tablets with SD IND-ARG (TAB SD IND-ARG) were compared to those of tablets containing a physical mixture of crystalline IND and ARG (TAB PM IND-ARG) and to the dissolution of pure spray dried powder. Concerning tableting, the developed formulation allowed for the preparation of tablets with a broad range of compaction pressures resulting in different porosities and tensile strengths. XRPD results showed that, overall, no crystallization occurred neither during tableting nor during long-term storage. Dissolution profiles of TAB SD IND-ARG showed an immediate release of IND by erosion. The solubility of crystalline IND was exceeded by a factor of about 4, which was accompanied by a slow crystallization. For TAB PM IND-ARG, an in situ amorphization of IND in the presence of ARG was observed. As a result, a supersaturation was obtained, too, followed by a faster crystallization compared to TAB SD IND-ARG. In conclusion, the AUC24h of TAB SD IND-ARG was twofold higher than the AUC24h of TAB PM IND-ARG. Interestingly, different plateaus were obtained for TAB SD IND-ARG, TAB PM IND-ARG and pure SD IND-ARG after 24h dissolution, which could be explained by the formation of different polymorphic forms of indomethacin.


Co-amorphous; Dissolution; In situ amorphization; Physical stability; Polymorphism; Tableting

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