NOVEL COMPOSITIONS
Provided are pharmaceutical compositions comprising (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form. The compositions are formulated for providing a sustained release of enantiomerically pure (1R,5S)-1-(naphthalene-2-yl)-3-azabicyclo[3.1.0]hexane. The compositions are substantially free of the other (−) enantiomer of the compound.
1 . A sustained release pharmaceutical composition comprising (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form, wherein 40-60% of the (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane is released and dissolved within 4 hours or less as measured in 900 mL water using USP Apparatus 2 paddle at 50 rpm and at 37° C.±0.5.
2 - 5 . (canceled)
6 . The composition of claim 1 , wherein the composition comprises less than or equal to 5% w/w of the corresponding (−) enantiomer.
7 . The composition of claim 1 , wherein the composition comprises less than or equal to 2% w/w of the corresponding (−) enantiomer.
8 . The composition of claim 1 , wherein the composition comprises less than or equal to 1% w/w of the corresponding (−) enantiomer.
9 - 10 . (canceled)
11 . The composition of claim 1 , wherein the (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane is in pharmaceutically acceptable salt form and is (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.
12 . The composition of claim 1 , wherein the composition comprises 100 mg to 300 mg of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form.
13 . (canceled)
14 . The composition of claim 1 , wherein the compositions comprises 100 mg to 200 mg of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form.
15 - 16 . (canceled)
17 . The composition of claim 1 , wherein the composition comprises 10-30% w/w of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane, in free or pharmaceutically acceptable salt form.
18 . The composition of claim 1 , wherein the composition further comprises hydroxypropyl methylcellulose.
19 . The composition of claim 18 , wherein the composition comprises 20-50% w/w of hydroxypropyl methylcellulose.
20 . The composition of claim 18 , wherein the degree of methoxy substitution of the hydroxypropyl methylcellulose is 19-24%.
21 . The composition of claim 18 , wherein the degree of hydroxypropoxy substitution of the hydroxypropyl methylcellulose is 4-12%.
22 . The composition of claim 18 , wherein the hydroxypropyl methylcellulose is hypromellose 2208.
23 . The composition of claim 18 , wherein the hydroxypropyl methylcellulose has a nominal viscosity of 4,000 mPA·s.
24 . The composition of claim 18 , wherein the hydroxypropyl methylcellulose has a viscosity of 2,600 to 5,000 mPA·s.
25 . The composition of claim 1 , wherein the composition further comprises alpha-lactose monohydrate.
26 . The composition of claim 25 , wherein the composition comprises 20-50% w/w of alpha-lactose monohydrate.
27 . The composition of claim 25 , wherein the composition comprises milled alpha-lactose monohydrate.
28 . The composition of claim 1 , wherein the composition comprises a co-processed mixture of hydroxpropyl methylcellulose and alpha-lactose monohydrate.
29 . The composition of claim 28 , wherein the mixture comprises equal parts of the hydroxpropyl methylcellulose and alpha-lactose monohydrate.
30 . The composition of claim 28 , wherein the mixture comprises particles of hydroxpropyl methylcellulose and alpha-lactose monohydrate with d 50 (median diameter) in the range of 100 mm to 200 mm.
31 . The composition of claim 28 , wherein the mixture comprises particles of hydroxpropyl methylcellulose and alpha-lactose monohydrate wherein the particle size distribution is as follows:
<63 mm≦25%
<100 mm: 35%
<250 mm≧80%.
32 . The composition of claim 28 , wherein the composition comprises 60-80% w/w of the mixture.
33 . The composition of claim 1 , wherein the composition further comprises a lubricant.
34 . The composition of claim 33 , wherein the lubricant is one or more of glyceryl behenate, magnesium stearate, talc, and sodium stearyl fumarate.
35 . The composition of claim 33 , wherein the composition comprises 0.1 to 1% w/w of the lubricant.
36 . The composition of claim 33 , wherein the composition comprises 0.1 to 1% w/w of magnesium stearate.
37 - 45 . (canceled)
46 . The composition of claim 1 , wherein 60-90% of the (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane is released and dissolved within 8 hours or less as measured in 900 mL water using USP Apparatus 2 paddle at 50 rpm and at 37° C.±0.5.