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Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers.
J Pharm Sci. 2017 01; 106(1):302-312.JP

Abstract

Co-amorphous drug-amino acid systems have gained growing interest as an alternative to common amorphous formulations which contain polymers as stabilizers. Several preparation methods have recently been investigated, including vibrational ball milling on a laboratory scale or spray drying in a larger scale. In this study, the feasibility of hot melt extrusion for continuous manufacturing of co-amorphous drug-amino acid formulations was examined, challenging the fact that amino acids melt with degradation at high temperatures. Furthermore, the need for an addition of a polymer in this process was evaluated. After a polymer screening via the solvent evaporation method, co-amorphous indomethacin-arginine was prepared by a melting-solvent extrusion process without and with copovidone. The obtained products were characterized with respect to their solid-state properties, non-sink dissolution behavior, and stability. Results were compared to those of spray-dried formulations with the same compositions and to spray-dried indomethacin-copovidone. Overall, stable co-amorphous systems could be prepared by extrusion without or with copovidone, which exhibited comparable molecular interaction properties to the respective spray-dried products, while phase separation was detected by differential scanning calorimetry in several cases. The formulations containing indomethacin in combination with arginine and copovidone showed enhanced dissolution behavior over the formulations with only copovidone or arginine.

Authors+Show Affiliations

Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf 40225, Germany.Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark.Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark.Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf 40225, Germany.Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf 40225, Germany. Electronic address: Kleinebudde@hhu.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27817830

Citation

Lenz, Elisabeth, et al. "Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers." Journal of Pharmaceutical Sciences, vol. 106, no. 1, 2017, pp. 302-312.
Lenz E, Löbmann K, Rades T, et al. Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers. J Pharm Sci. 2017;106(1):302-312.
Lenz, E., Löbmann, K., Rades, T., Knop, K., & Kleinebudde, P. (2017). Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers. Journal of Pharmaceutical Sciences, 106(1), 302-312. https://doi.org/10.1016/j.xphs.2016.09.027
Lenz E, et al. Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers. J Pharm Sci. 2017;106(1):302-312. PubMed PMID: 27817830.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers. AU - Lenz,Elisabeth, AU - Löbmann,Korbinian, AU - Rades,Thomas, AU - Knop,Klaus, AU - Kleinebudde,Peter, Y1 - 2016/11/03/ PY - 2016/07/26/received PY - 2016/09/26/revised PY - 2016/09/27/accepted PY - 2016/11/8/pubmed PY - 2017/12/13/medline PY - 2016/11/8/entrez KW - amino acid KW - co-amorphous KW - dissolution KW - hot melt extrusion KW - physical stability KW - polymer KW - spray drying SP - 302 EP - 312 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 106 IS - 1 N2 - Co-amorphous drug-amino acid systems have gained growing interest as an alternative to common amorphous formulations which contain polymers as stabilizers. Several preparation methods have recently been investigated, including vibrational ball milling on a laboratory scale or spray drying in a larger scale. In this study, the feasibility of hot melt extrusion for continuous manufacturing of co-amorphous drug-amino acid formulations was examined, challenging the fact that amino acids melt with degradation at high temperatures. Furthermore, the need for an addition of a polymer in this process was evaluated. After a polymer screening via the solvent evaporation method, co-amorphous indomethacin-arginine was prepared by a melting-solvent extrusion process without and with copovidone. The obtained products were characterized with respect to their solid-state properties, non-sink dissolution behavior, and stability. Results were compared to those of spray-dried formulations with the same compositions and to spray-dried indomethacin-copovidone. Overall, stable co-amorphous systems could be prepared by extrusion without or with copovidone, which exhibited comparable molecular interaction properties to the respective spray-dried products, while phase separation was detected by differential scanning calorimetry in several cases. The formulations containing indomethacin in combination with arginine and copovidone showed enhanced dissolution behavior over the formulations with only copovidone or arginine. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/27817830/Hot_Melt_Extrusion_and_Spray_Drying_of_Co_amorphous_Indomethacin_Arginine_With_Polymers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(16)41764-8 DB - PRIME DP - Unbound Medicine ER -