# US 7,745,429 B2 · Crystal forms of olanzapine and processes for their preparation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,745,429 B2 - Document ID: US7745429B2 - Status: Granted - Kind: B2 - Application number: 10/521,646 - Filed: 2003-07-14 - Published: 2006-02-23 - Granted: 2010-06-29 - Earliest claimed: 2002-07-15 - Assignees: KRKA, d.d. Novo mesto - Inventors: Berta Kotar Jordan; Franc Vrecer; Marija Grcman - Web page: https://patentgrep.com/patent/US7745429B2 ## CPC - C07D 495/04: Ortho-condensed systems - A61K 31/551: having two nitrogen atoms, e.g. dilazep - A61P 25/00: Drugs for disorders of the nervous system - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The invention relates to a process for the preparation of form I of olanzapine, crystallized from a solvent mixture which comprises 2-propanol, some pseudopolymorphic forms, namely solvates of olanzapine, a new polymorphic form A of olanzapine, and processes for the preparation thereof. ## Claims ### Claim 1 Acetonitrile/methylene chloride/water mixed solvate of olanzapine characterized by an x-ray powder diffraction pattern (2 theta) as follows: 8.76, 19.39, 20.12. ### Claim 2 (depends on 1) Acetonitrile/methylene chloride/water mixed solvate of olanzapine according to claim 1, characterized by an x-ray powder diffraction pattern (2 theta) as follows: 8.76, 18.29, 19.39, 19.66, 20.12, 23.13, 23.62, 25.08. ### Claim 3 Acetonitrile/water mixed solvate of olanzapine characterized by an x-ray powder diffraction pattern (2 theta) as follows: 8.76, 9.10, 14.05, 19.37, 20.10, 24.55, 25.92, 27.96. ### Claim 4 (depends on 3) Acetonitrile/water mixed solvate of olanzapine according to claim 3, characterized by an x-ray powder diffraction pattern (2 theta) as follows: 8.76, 9.10, 14.05, 14.44, 18.30, 18.67, 18.84, 19.37, 19.68, 20.10, 20.54, 21.65, 22.79, 23.12, 23.62, 24.55, 25.06, 25.92, 27.96, 28.44. ### Claim 5 2-propanol solvate of olanzapine characterized by an x-ray powder diffraction pattern as follows: 8.74, 14.05, 19.38, 22.65, 23.03, 24.46, 25.92, 28.36. ### Claim 6 (depends on 5) 2-propanol solvate of olanzapine according to claim 5, characterized by an x-ray powder diffraction pattern as follows: 8.74, 14.05, 14.41, 17.77, 18.22, 18.76, 19.38, 19.81, 19.95, 20.54. 20,96, 21.64, 22.26, 22.65, 23.03, 23.58, 23.90, 24.46, 25.03, 25.39, 25.92, 26.63, 27.47, 27.95, 28.36. ### Claim 7 Methylene chloride solvate IA of olanzapine characterized by an x-ray powder diffraction pattern as follows: 10.80, 14.25, 19.22, 22.78, 24.53. ### Claim 8 (depends on 7) Methylene chloride solvate IA of olanzapine according to claim 7, characterized by an x-ray powder diffraction pattern as follows: 8.85, 10.80, 12.89, 14.09, 14.25, 18.37, 18.81, 19.22, 19.41, 19.57, 20.07, 20.80, 21.00, 21.71, 22.06, 22.25, 22.78, 23.14, 23.62, 24.03, 24.53, 25.04, 25.43, 26.67, 27.51, 28.00, 28.45, 28.70. ### Claim 9 Methylene chloride solvate IB of olanzapine characterized by an x-ray powder diffraction pattern as follows: 9.30, 10.80, 14.25, 14.98, 15.94, 19.23, 20.04. ### Claim 10 (depends on 9) Methylene chloride solvate IB of olanzapine according to claim 9, characterized by an x-ray powder diffraction pattern as follows: 8.43, 8.86, 9.30, 10.80, 14.25, 14.98, 15.94, 16.88, 17.79, 18.40, 18.57, 18.83, 19.23, 19.57, 20.04, 20.79, 21.01, 21.68, 22.06, 22.23, 23.57, 24.02, 24.89, 25.12, 25.46, 26.38, 26.56, 27.50, 28.06, 28.71, 29.02. ### Claim 11 (depends on 1) Process for preparing anhydrous forms of olanzapine by drying at least one solvate according to claim 1. ### Claim 12 (depends on 7) Process wherein the anhydrous form I of olanzapine is prepared by drying at least one solvate according to claim 7. ### Claim 13 Form A of olanzapine characterized by an x-ray powder diffraction pattern as follows: 11.52, 12.00, 13.35, 13.56, 14.21, 15.47, 16.69, 19.16, 20.25 20.69, 22.12, 24.33, 26.88, 27.13. ### Claim 14 (depends on 13) Form A of olanzapine according to claim 13, characterized by an x-ray powder diffraction pattern as follows: 11.52, 11.83, 12.00, 13.35, 13.56, 14.21, 15.47, 16.69, 17.83, 19.16, 20.25, 20.69, 21.65, 22.12, 23.21, 24.33, 26.88, 27.13, 28.57. ### Claim 15 (depends on 13) Form A of olanzapine according to claim 13, which is in essential pure form. ### Claim 16 (depends on 13) Form A of olanzapine according to claim 13, which is anhydrous. ### Claim 17 (depends on 13) Process for preparing form A of olanzapine as defined in claim 13, comprising the steps of dissolving any form of olanzapine in a mixture of acetonitrile with a solvent in which olanzapine is soluble or in a solvent in which olanzapine is soluble, heating the mixture to obtain a clear solution, optionally filtering the solution, partly evaporating the solvent and isolating the product. ### Claim 18 (depends on 13) Pharmaceutical composition in solid state which comprises form A of olanzapine according to claim 13. ### Claim 19 (depends on 3) Process for preparing anhydrous forms of olanzapine by drying at least one solvate according to claim 3. ### Claim 20 (depends on 5) Process for preparing anhydrous forms of olanzapine by drying at least one solvate according to claim 5. ### Claim 21 (depends on 7) Process for preparing anhydrous forms of olanzapine by drying at least one solvate according to claim 7. ### Claim 22 (depends on 9) Process for preparing anhydrous forms of olanzapine by drying at least one solvate according to claim 9. ### Claim 23 (depends on 9) Process wherein the anhydrous form I of olanzapine is prepared by drying at least one solvate according to claim 9.