title: Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine.
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.
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lenz
authors.affiliation: Department of Pharmacy, University of Copenhagen, Denmark.
authors.forename: Katrine Tarp
authors.initials: KT
authors.lastname: Jensen
authors.affiliation: Department of Pharmacy, University of Copenhagen, Denmark.
authors.forename: Lasse Ingerslev
authors.initials: LI
authors.lastname: Blaabjerg
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Knop
authors.affiliation: Department of Pharmacy, University of Copenhagen, Denmark.
authors.forename: Holger
authors.initials: H
authors.lastname: Grohganz
authors.affiliation: Department of Pharmacy, University of Copenhagen, Denmark.
authors.forename: Korbinian
authors.initials: K
authors.lastname: Löbmann
authors.affiliation: Department of Pharmacy, University of Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany. Electronic address: Kleinebudde@hhu.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Kleinebudde
mesh_terms: D001120:Arginine / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D007213:Indomethacin / Q000737:chemistry*; D016062:Porosity; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D013718:Tensile Strength
chemical_list: D013607:Tablets; D001120:Arginine; D007213:Indomethacin
keywords: Co-amorphous; Dissolution; In situ amorphization; Physical stability; Polymorphism; Tableting