Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine
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Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine. / Lenz, Elisabeth; Jensen, Katrine Birgitte Tarp; Blaabjerg, Lasse Ingerslev; Knop, Klaus; Grohganz, Holger; Löbmann, Korbinian; Rades, Thomas; Kleinebudde, Peter.
In: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Vol. 96, 10.2015, p. 44–52.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine
AU - Lenz, Elisabeth
AU - Jensen, Katrine Birgitte Tarp
AU - Blaabjerg, Lasse Ingerslev
AU - Knop, Klaus
AU - Grohganz, Holger
AU - Löbmann, Korbinian
AU - Rades, Thomas
AU - Kleinebudde, Peter
N1 - Copyright © 2015. Published by Elsevier B.V.
PY - 2015/10
Y1 - 2015/10
N2 - 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 24 h dissolution, which could be explained by the formation of different polymorphic forms of indomethacin.
AB - 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 24 h dissolution, which could be explained by the formation of different polymorphic forms of indomethacin.
U2 - 10.1016/j.ejpb.2015.07.011
DO - 10.1016/j.ejpb.2015.07.011
M3 - Journal article
C2 - 26197392
VL - 96
SP - 44
EP - 52
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
ER -
ID: 142208957