Compositions and methods for treating schizophrenia
The disclosure provides a novel polymorph of Compound (I): 2-((1-(2-(4-Fluorophenyl)-2-oxoethyl)piperidin-4-yl)methyl)isoindolin-1-one monohydrochloride dihydrate, i.e., Form (A) of Compound (I).HCl.2H 2 O. Pharmaceutical compositions comprising Form (A) of Compound (I).HCl.2H 2 O and related methods of treatment are also disclosed.
1. A pharmaceutical formulation comprising Compound (I);
wherein the formulation comprises a release modifier that provides a maximum plasma concentration (C max ) of Compound (I) or the polymorph form (A) of Compound (I).HCl.2H 2 O below 50 ng/mL when a dose of between about 1-100 mg of the formulation is administered to a human.
2. The pharmaceutical formulation of claim 1 , when Compound (I) is present as the polymorph form (A) of Compound (I).HCl.2H 2 O.
3. The pharmaceutical formulation of claim 2 , comprising about 10-75 mg or about 15-65 mg of Compound (I) or the polymorph form (A) of Compound (I).HCl.2H 2 O.
4. The pharmaceutical formulation of claim 2 , wherein the release modifier is a hypromellose.
5. The pharmaceutical formulation of claim 1 , further comprising a filler, a glidant, and a lubricant.
6. The pharmaceutical formulation of claim 1 , wherein the formulation provides a maximum plasma concentration (C max ) of BFB-520 below 10.0 ng/mL, or a maximum plasma concentration (C max ) of BFB-999 below 5.0 ng/mL, or an AUC of Compound (I) or the polymorph form (A) of Compound (I).HCl.2H 2 O below 400 hr*ng/mL, or an AUC of BFB-520 below 40 hr*ng/mL, or an AUC of BFB-999 below 40 hr*ng/mL.
7. The pharmaceutical formulation of claim 1 , wherein substantially all of the administered dose of Compound (I) or the polymorph form (A) of Compound (I).HCl.2H 2 O is released from the pharmaceutical formulation over 16-24 hours.
8. A method of treating a neuropsychiatric disease or disorder, comprising administering a therapeutically effective amount of the pharmaceutical formulation of claim 1 to a subject in need thereof.
9. The method of claim 8 , wherein the neuropsychiatric disease or disorder is schizophrenia.
10. The method of claim 8 , wherein the amount of Compound (I) or the polymorph form (A) of Compound (I).HCl.2H 2 O administered is in the range of about 1-100 mg.
11. The method of claim 10 , wherein the amount of Compound (I) or the polymorph form (A) of Compound (I).HCl.2H 2 O administered is in the range of about 10-75 mg or about 15-65 mg.
12. A method of treating a sleep disorder, comprising administering a therapeutically effective amount of the pharmaceutical formulation of claim 1 to a subject in need thereof.
13. The method of claim 12 , wherein at least one aspect of a sleep disorder is treated or diminished.
14. A kit comprising the pharmaceutical formulation of claim 1 , and instructions for use.