Crystalline forms of the di-sodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid
View Patent ↗The present invention relates to crystalline polymorphic forms of the di-sodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid, pharmaceutical compositions containing the same, methods of preparing the same, and methods for facilitating the delivery of active agents with the same.
1. A crystalline ethanol solvate of the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid exhibiting an X-ray powder diffraction pattern having at least one peak in degrees 2Θ±0.2°2Θ selected from 7.5, 14.1, 16.5, 18.5, 25, and 26.
2. The crystalline ethanol solvate of claim 1 , wherein the crystalline ethanol solvate exhibits an X-ray powder diffraction pattern having at least one peak in degrees 2Θ±0.2°2Θ selected from 16.5, 25, and 26.
3. A process for preparing Form I of the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid comprising the steps of:
(a) dissolving a monoethanol solvate of the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid of claim 1 in a mixture of acetonitrile and water; and
(b) cooling the solution prepared in step (a) to an effective temperature to yield Form I of the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid.
4. A process for preparing a monoethanol solvate (Form II) of the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid of claim 1 comprising the steps of:
(a) adding sodium hydroxide to a solution of N-(5-chlorosalicyloyl)-8-aminocaprylic acid and ethanol; and
(b) precipitating Form II of the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid from the solution.
5. A pharmaceutical composition comprising the crystalline ethanol solvate of the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid of claim 1 and a biologically active agent.
6. A pharmaceutical composition comprising the crystalline ethanol solvate of the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid of claim 2 and a biologically active agent.