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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.

Author information

1
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
2
Department of Pharmacy, University of Copenhagen, Denmark.
3
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany. Electronic address: Kleinebudde@hhu.de.

Abstract

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.

KEYWORDS:

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

PMID:
26197392
DOI:
10.1016/j.ejpb.2015.07.011
[Indexed for MEDLINE]

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