Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers.
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.
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf 40225, Germany.
Elisabeth
E
Lenz
Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark.
Korbinian
K
Löbmann
Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark.
Thomas
T
Rades
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf 40225, Germany.
Klaus
K
Knop
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf 40225, Germany. Electronic address: Kleinebudde@hhu.de.
Peter
P
Kleinebudde
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001120:Arginine / Q000737:chemistry*; D003890:Desiccation / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005615:Freezing; D006358:Hot Temperature; D007213:Indomethacin / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D012995:Solubility; D014753:Vinyl Compounds / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D001120:Arginine; D007213:Indomethacin
amino acid; co-amorphous; dissolution; hot melt extrusion; physical stability; polymer; spray drying