NANOSTRUCTURED COMPOSITION COMPRISING INDOMETHACINE, ITS PHARMACEUTICALLY ACCEPTABLE SALTS AND CO-CRYSTALS AND PROCESS FOR THE PREPARATION THEREOF

摘要

The invention relates to a nanostructured (nanoparticular) composition comprising Indomethacine, its pharmaceutically acceptable salts and co-crystals, processes for the preparation thereof, and compositions useful for pharmaceutical applications. The size of the nanoparticles according to the invention is smaller than 500 nm. Indomethacine (INN) or Indomethacine (USAN, previously BAN) is a non-steroidal anti-inflammatory drug (NSAID), which is used for the treatment of fever, inflammation, spasm, swells and inflammations. The machanism of action of Indomethacine is the inhibition of the synthesis of prostaglandin. It is marketed under the trade names of Indocin, Indocid, Indochron E-R, and Indocin-SR.

主权项

1. A stable nanostructured indomethacin composition comprising
(a) indomethacin or pharmaceutically acceptable salts, cocrystals or mixtures thereof; and (b) at least one polyelectrolyte and/or stabilizer or mixtures thereof for stabilization of the nanoparticles; and optionally further stabilizers for steric and electrostatic stabilization; wherein the nanostructured particles have a particle size of 500 nm or less; and wherein the composition is prepared by controlled nano-precipitation in a flow reactor, preferably in a microfluidic based flow reactor; and preferably comprises stabilizers; and wherein the stabilizer is selected from cellulose or derivatives thereof, polysaccharides, such as mannitol or sorbitol, polyvinylpyrrolidone, gelatin, cetostearyl alcohol, polyethylene glycols, acetic acid, polyvinylpyrrolidone-vinyl acetate copolymers, sodium dodecyl benzene sulfonate, sodium dodecyl-benzoyl sulfonate, tocopheryl polyethylene glycol succinate, urea, citric acid, sodium acetate, polyoxyethylene stearate, polyvinyl alcohol (PVA), polymethacrylate based polymers and copolymers, 4-(1,1,3,3-tetramethylbuthyl)-phenol polymer with ethylene oxide and formaldehyde groups (eg. tyloxapol, Superione and triton), poloxamers (eg. Pluronics, which are block copolymers of propylene oxide and ethylene oxide), poloxamines (eg. Tetronic, which is a tetrafunctional block copolymer), polyethylene glycol-polycaprolactam-polyvinyl acetate graft copolymer (Soluplus), D-alpha-tocopheryl polyethylene glycol succinate, poly(2-ethyl-2-oxazoline), poly(methyl vinyl ether), random copolymers of vinyl pyrrolidone and vinyl acetate, such as Plasdone S630, and mixtures thereof.