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

Elisabeth Lenz; Katrine Birgitte Tarp Jensen; Lasse Ingerslev Blaabjerg; Klaus Knop; Holger Grohganz; Korbinian Löbmann; Thomas Rades; Peter Kleinebudde

doi:10.1016/j.ejpb.2015.07.011

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

Elisabeth Lenz, Katrine Birgitte Tarp Jensen, Lasse Ingerslev Blaabjerg, Klaus Knop, Holger Grohganz, Korbinian Löbmann, Thomas Rades, Peter Kleinebudde

46 Citations (Scopus)

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 AUC_24h of TAB SD IND–ARG was twofold higher than the AUC_24h 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.

Original language	English
Journal	European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
Volume	96
Pages (from-to)	44–52
Number of pages	9
ISSN	0939-6411
DOIs	https://doi.org/10.1016/j.ejpb.2015.07.011
Publication status	Published - 25 Jul 2015

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Lenz, E., Jensen, K. B. T., Blaabjerg, L. I., Knop, K., Grohganz, H., Löbmann, K., Rades, T., & Kleinebudde, P. (2015). Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 96, 44–52. https://doi.org/10.1016/j.ejpb.2015.07.011

Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine. / Lenz, Elisabeth; Jensen, Katrine Birgitte Tarp; Blaabjerg, Lasse Ingerslev et al.

In: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Vol. 96, 25.07.2015, p. 44–52.

Research output: Contribution to journal › Journal article › Research › peer-review

Lenz, E, Jensen, KBT, Blaabjerg, LI, Knop, K, Grohganz, H , Löbmann, K , Rades, T & Kleinebudde, P 2015, 'Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine', European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, vol. 96, pp. 44–52. https://doi.org/10.1016/j.ejpb.2015.07.011

Lenz E, Jensen KBT, Blaabjerg LI, Knop K, Grohganz H , Löbmann K et al. Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2015 Jul 25;96:44–52. doi: 10.1016/j.ejpb.2015.07.011

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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 24 h dissolution, which could be explained by the formation of different polymorphic forms of indomethacin.",

author = "Elisabeth Lenz and Jensen, {Katrine Birgitte Tarp} and Blaabjerg, {Lasse Ingerslev} and Klaus Knop and Holger Grohganz and Korbinian L{\"o}bmann and Thomas Rades and Peter Kleinebudde",

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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

PY - 2015/7/25

Y1 - 2015/7/25

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

SN - 0939-6411

VL - 96

SP - 44

EP - 52

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

ER -

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

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