US-20260125393-A1 - SALTS, CRYSTAL FORMS, AND PRODUCTION METHODS THEREOF

Abstract

Provided are salts of (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine and various of crystal forms thereof, and compositions, medicaments, pharmaceutically acceptable formulations thereof, and methods of making same. In addition, provided are compounds comprising specific particle size distributions of crystalline (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine HCl and methods of making and modulating the particle size distributions.

Inventors

• Andrea Bauer
• Nandkumar Nivritti Bhogle
• Xiaoxia Chen
• Shahla Jamzad
• Robert Joseph Prytko
• Kostas Saranteas
• Michael Joseph Sizensky
• Harold Scott Wilkinson
• Haitao Zhang

Assignees

• SUMITOMO PHARMA AMERICA, INC.

Dates

Publication Date

20260507

Application Date

20250702

Claims (20)

1. 1 - 53 . (canceled)
2. 54 . A formulation comprising (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine R-mandelate and one or more excipients, wherein: the amount of (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine R-mandelate is about 2 to about 80% w/w, on a free base basis.
3. 55 . The formulation of claim 54 , wherein the formulation is a tablet.
4. 56 . The formulation of claim 54 , wherein the amount of (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine R-mandelate is one of: i) about 50 to about 80% w/w; ii) about 60 to about 80% w/w; and iii) about 70% w/w.
5. 57 . The formulation of claim 54 , wherein the excipient comprises one or more fillers, one or more disintegrants, and/or one or more lubricants.
6. 58 . The formulation of claim 57 , wherein one or more of: i) the one or more fillers is microcrystalline cellulose, mannitol, or a mixture thereof; ii) the one or more disintegrants is sodium starch glycolate; and iii) the one or more lubricants is magnesium stearate.
7. 59 . The formulation of claim 57 , wherein one or more of: i) the amount of the one or more fillers is about 10 to about 50% w/w; ii) the amount of the one or more disintegrants is about 0.5 to about 10% w/w; and iii) the amount of the one or more lubricants is about 0.1 to about 0.5% w/w.
8. 60 . A method of treating a neurological disease or disorder, comprising administering to a subject a therapeutically effective amount of the formulation of claim 54 .
9. 61 . The method of claim 60 , wherein the neurological disease or disorder is schizophrenia.
10. 62 . The method of claim 60 , wherein the neurological disease or disorder is the schizophrenia spectrum disorder, schizophrenia negative symptoms, attenuated psychosis syndrome, prodromal schizophrenia, delusional disorder, psychosis, attenuated psychosis syndrome, psychotic disorder, delirium, Tourette's syndrome, post-traumatic stress disorder, behavior disorder, affective disorder, depression, bipolar disorder, major depressive disorder, dysthymia, bipolar disorder, manic disorder, seasonal affective disorder, obsessive-compulsive disorder, narcolepsy, REM behavior disorder, substance abuse or dependency, Lesch-Nyhan disease, Wilson's disease, autism, Alzheimer's disease agitation and psychosis, or Huntington's chorea.
11. 63 . The method of claim 62 , wherein the schizophrenia spectrum disorder is selected from schizophrenia, attenuated psychosis syndrome, prodromal schizophrenia, schizoid personality disorder, and schizotypal personality disorder.
12. 64 . A formulation comprising (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine mesylate and one or more excipients, wherein: the amount of (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine mesylate is about 2 to about 80% w/w, on a free base basis.
13. 65 . The formulation of claim 64 , wherein the excipient comprises one or more fillers, one or more disintegrants, and/or one or more lubricants.
14. 66 . The formulation of claim 65 , wherein one or more of: i) the one or more fillers is microcrystalline cellulose, mannitol, or a mixture thereof; ii) the one or more disintegrants is sodium starch glycolate; and iii) the one or more lubricants is magnesium stearate.
15. 67 . A method of treating a neurological disease or disorder, comprising administering to a subject a therapeutically effective amount of the formulation of claim 64 .
16. 68 . The method of claim 67 , wherein the neurological disease or disorder is schizophrenia.
17. 69 . A formulation comprising (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine L-tartrate and one or more excipients, wherein: the amount of (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine L-tartrate is about 2 to about 80% w/w, on a free base basis.
18. 70 . The formulation of claim 69 , wherein the excipient comprises one or more fillers, one or more disintegrants, and/or one or more lubricants.
19. 71 . The formulation of claim 70 , wherein one or more of: i) the one or more fillers is microcrystalline cellulose, mannitol, or a mixture thereof; ii) the one or more disintegrants is sodium starch glycolate; and iii) the one or more lubricants is magnesium stearate.
20. 72 . A method of treating a neurological disease or disorder, comprising administering to a subject a therapeutically effective amount of the formulation of claim 69 .

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 62/710,416, filed Feb. 16, 2018, the contents of which are incorporated by reference herein in their entirety. FIELD Provided herein are (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine salts and polymorphic forms of thereof, formulations comprising them, methods of making them, and methods for their use for the treatment of various diseases and disorders. Provided herein are pharmaceutical compositions comprising (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride and polymorphic forms of thereof, methods of making the compositions, and methods for their use for the treatment of various diseases and disorders. BACKGROUND (S)-(4,5-Dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine is described in U.S. Pat. No. 8,710,245 (the '245 patent). It has the following chemical structure: Uses of (S)-(4,5-Dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine in the treatment, prevention, or management of affective disorders and other various CNS disorders are also disclosed in the '245 patent. Drug substances are most frequently administered orally by means of solid dosage forms such as tablets and capsules. Tablets remain popular as a dosage form because of the advantages afforded both to the manufacturer (e.g., simplicity and economy of preparation, stability and convenience in packaging, shipping and dispensing) and to the subject (e.g., accuracy of dosage, compactness, portability, blandness of taste and ease of administration). The preparation of tablets almost universally requires that the active pharmaceutical ingredient (API) be a solid. In the manufacture of solid APIs, it is necessary to obtain products with reproducible properties, including chemical purity and composition. For crystalline solid APIs that exhibit polymorphism, it is important to produce the desired polymorph to assure the bioavailability and stability of the drug substance. In addition to considerations of polymorphism, the manufacture of tablets is often sensitive to crystal size and morphology. While the target of many crystallization operations is to produce crystals large enough to be isolated easily on standard filtration equipment, smaller particle sizes are often desired to enhance the dissolution rate, improve bioavailability, and facilitate tablet formation. A reliable, reproducible process for preparing shelf-stable, readily bioavailable, pharmaceutical dosage forms for (S)-(4,5-Dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine would be highly desirable. SUMMARY The present disclosure provides salts of (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine, formulations or compositions comprising these salts, method of preparing the compound, salts, formulations or compositions thereof, as well as polymorphs of the salts. In various aspects, the present inventions relate to substantially pure crystalline forms of (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride, methods of producing same, compositions, medicaments and formulations including same, and methods of treating various diseases and disorders using same. In various aspects, provided are crystalline forms of (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride, ((S)-TPMA HCl). In various embodiments, provided are crystalline forms of (S)-(4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride of crystalline Form A. In various embodiments, crystalline (S) (4,5-dihydro-7H-thieno[2,3-c]pyran-7-yl)-N-methylmethanamine hydrochloride of Form A is characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 9.6±0.2°, 14.9±0.2°, 20.5±0.2°, and 25.1±0.2°, in various embodiments further comprising peaks at 20.2±0.2° and 20.8±0.2°, and in various embodiments further comprising peaks at 20.2±0.2° and 20.8±0.2° and a prominent peak at two or more of 17.9±0.2°, 24.8±0.2° and 27.1±0.2°. In various embodiments, the present inventions provide substantially enantiomerically pure crystalline forms of (S)-TPMA HCl of Form A. For example, in various embodiments, the present inventions provide crystalline forms of TPMA HCl that contain greater than about 90% (S)-TPMA HCl and less than about 10% of (R)-TPMA HCl, greater than about 95% (S)-TPMA HCl and less than about 5% of (R)-TPMA HCl, greater than about 97% (S)-TPMA HCl and less than about 3% of (R)-TPMA HCl, greater than about 99% (S)-TPMA HCl and less than about 1% of (R)-TPMA HCl, greater than about 99.5% (S)-TPMA HCl and less than about 0.5% of (R)-TPMA HCl, greater than about 99.7% (S)-TPMA HCl and less than about 0.3% of (R)-TPMA HCl, or greater than about 99.9% (S)-TPMA HCl and less than about 0.1% of (R)-TPMA HCl. In various embodiments, the present inventions provide substantially chemically pure crystalline forms of (S)-TPMA HCl of Form A. For example, in