High Dosage Valbenazine Formulation and Compositions, Methods, and Kits Related Thereto

1 . A solid pharmaceutical composition comprising:

valbenazine, or a pharmaceutically acceptable salt thereof;

silicified microcrystalline cellulose;

isomalt;

hydroxypropyl methylcellulose;

partially pregelatinized maize starch; and

magnesium stearate.

2 . The solid pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable salt of valbenazine is valbenazine ditosylate.

3 . The solid pharmaceutical composition of claim 1 or 2 , wherein valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level ranging from about 20-160 mg as measured as the free base.

4 . The solid pharmaceutical composition of any one of claims 1 - 3 , wherein valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 20 mg as measured as the free base.

5 . The solid pharmaceutical composition of any one of claims 1 - 3 , wherein valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 40 mg as measured as the free base.

6 . The solid pharmaceutical composition of any one of claims 1 - 3 , wherein valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 60 mg as measured as the free base.

7 . The solid pharmaceutical composition of any one of claims 1 - 3 , wherein valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 80 mg as measured as the free base.

8 . The solid pharmaceutical composition of any one of claims 1 - 3 , wherein valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 120 mg as measured as the free base.

9 . The solid pharmaceutical composition of any one of claims 1 - 3 , wherein valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 160 mg as measured as the free base.

10 . The solid pharmaceutical composition of any one of claims 1 - 9 , wherein valbenazine ditosylate is present at a level of at least 30% by weight of the total weight of the unit dosage form.

11 . The solid pharmaceutical composition of any one of claims 1 - 9 , wherein valbenazine ditosylate is present at a level of at least 35% by weight of the total weight of the unit dosage form.

12 . The solid pharmaceutical composition of any one of claims 1 - 9 , wherein valbenazine ditosylate is present at a level of at least 38% by weight of the total weight of the unit dosage form.

13 . The solid pharmaceutical composition of any one of claims 1 - 9 , wherein valbenazine ditosylate is present at a level of at least 40% by weight of the total weight of the unit dosage form.

14 . The solid pharmaceutical composition of any one of claims 1 - 9 , wherein valbenazine ditosylate is present at a level of at least 45% by weight of the total weight of the unit dosage form.

15 . The solid pharmaceutical composition of any one of claims 1 - 14 , wherein the solid pharmaceutical composition is in unit dosage form suitable for oral administration.

16 . The solid pharmaceutical composition of any one of claims 1 - 15 , wherein the unit dosage form is formulated for dosing once daily.

17 . The solid pharmaceutical composition of any one of claims 1 - 16 , wherein the unit dosage form is in capsule form.

18 . The solid pharmaceutical composition of any one of claims 1 - 17 , wherein the capsule form comprises a capsule of size 0 or smaller.

19 . The solid pharmaceutical composition of any one of claims 1 - 18 , wherein the capsule form comprises a capsule of size 1.

20 . The solid pharmaceutical composition of any one of claims 1 - 19 , wherein the capsule has at least 80% dissolution at 30 minutes in a USP Paddle Dissolution Method 2 apparatus and 0.1 N HCl medium.

21 . The solid pharmaceutical composition of any one of claims 1 - 20 , wherein the solid pharmaceutical composition has a bulk density of at least about 0.5 mg/mL.

22 . The solid pharmaceutical composition of any one of claims 1 - 21 , wherein the solid pharmaceutical composition has a tapped density of at least about 0.6 mg/mL.

23 . The solid pharmaceutical composition of any one of claims 1 - 22 , wherein the valbenazine ditosylate has a d(0.9) particle size distribution less than 100 μm.

24 . An oral dosage product comprising the pharmaceutical composition of any one of claims 1 - 23 .

25 . A unit dosage form comprising a capsule of size 1 or smaller and at least 80 mg of valbenazine, or a pharmaceutically acceptable salt thereof, as measured as the free base.

26 . The unit dosage form of claim 25 comprising a capsule of size 2 or smaller.

27 . The unit dosage form of claim 25 or 26 , wherein the pharmaceutically acceptable salt of valbenazine is valbenazine ditosylate.

28 . A unit dosage form comprising a capsule of size 2 or smaller and at least 20 mg of valbenazine, or a pharmaceutically acceptable salt thereof, as measured as the free base.

29 . The unit dosage form of claim 28 comprising at least 40 mg valbenazine, or a pharmaceutically acceptable salt thereof, as measured as the free base.

30 . The unit dosage form of claim 28 comprising at least 60 mg valbenazine, or a pharmaceutically acceptable salt thereof, as measured as the free base.

31 . The unit dosage form of any one of claims 28 - 30 , wherein the pharmaceutically acceptable salt of valbenazine is valbenazine ditosylate.

32 . A unit dosage form comprising a capsule of size 0 or smaller and at least 120 mg of valbenazine, or a pharmaceutically acceptable salt thereof, as measured as the free base.

33 . A unit dosage form comprising valbenazine ditosylate having a w/w % of at least 35%.

34 . The unit dosage form of claim 32 , wherein the valbenazine ditosylate has a w/w % of at least 38%.

35 . The unit dosage form of claim 32 , wherein the valbenazine ditosylate has a w/w % of at least 40%.

36 . The unit dosage form of any one of claims 33 - 35 , further comprising:

silicified microcrystalline cellulose;

isomalt;

hydroxypropyl methylcellulose;

partially pregelatinized maize starch; and

magnesium stearate.

37 . A unit dosage form of a pharmaceutical composition comprising:

valbenazine ditosylate having a w/w % of about 40%;

silicified microcrystalline cellulose having a w/w % of about 25%;

isomalt having a w/w % of about 20%;

hydroxypropyl methylcellulose having a w/w % of about 5%;

partially pregelatinized maize starch having a w/w % of about 7.5%; and

magnesium stearate having a w/w % of about 2.5%.

38 . A method comprising orally administering a unit dosage form of the solid pharmaceutical composition of any one of claims 1 - 37 to a subject in need thereof.

39 . The method of claim 38 , wherein the subject has a neurological or psychiatric disease or disorder.

40 . The method of claim 38 , wherein the subject has a hyperkinetic movement disorder.

41 . The method of claim 38 , wherein the subject has tardive dyskinesia.

42 . The method of claim 38 , wherein the subject has Tourette's syndrome.

43 . The method of claim 38 , wherein the subject has Huntington's disease.

44 . The method of claim 38 , wherein the subject has tics.

45 . The method of claim 38 , wherein the subject has chorea associated with Huntington's disease.

46 . The method of claim 38 , wherein the subject has ataxia, chorea, dystonia, hemifacial spasm, ton's disease, myoclonus, restless leg syndrome, or tremors.

47 . The method of claim 38 wherein the subject has hyperkinetic movement disorder, mood disorder, bipolar disorder, schizophrenia, schizoaffective disorder, mania in mood disorders, depression in mood disorder, treatment-refractory obsessive compulsive disorder, neurological dysfunction associated with Lesch-Nyhan syndrome, agitation associated with Alzheimer's disease, Fragile X syndrome or Fragile X-associated tremor-ataxia syndrome, autism spectrum disorder, Rett syndrome, or chorea-acanthocytosis.

48 . The method of any one of claims 38 - 47 , wherein oral administration comprises administering a first unit dosage form to the subject followed by administration of a second unit dosage form to the subject, wherein valbenazine or pharmaceutically acceptable salt thereof is present in the first unit dosage form at a lower level than present in the second unit dosage form.

49 . The method of claim 48 , wherein valbenazine or pharmaceutically acceptable salt thereof is present in the first unit dosage form at a level of about 40 mg as measured as the free base.

50 . The method of any one of claims 48 - 49 wherein valbenazine or pharmaceutically acceptable salt thereof is present in the second unit dosage form at a level of about 80 mg as measured as the free base.

51 . The method of any one of claims 48 - 50 , wherein the first unit dosage form is administered to the subject for days, weeks or months prior to administration of the second unit dosage form to the subject.

52 . The method of any one of claims 48 - 51 , wherein the first unit dosage form is administered to the subject daily for one week prior to administration of the second unit dosage form to the subject.

53 . A method for treating a neurological or psychiatric disease or disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the solid pharmaceutical composition of any one of claims 1 - 23 , the oral dosage product of claim 24 , or the unit dosage form of any one of claims 25 - 37 .

54 . A method for treating a hyperkinetic movement disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the solid pharmaceutical composition of any one of claims 1 - 23 , the oral dosage product of claim 24 , or the unit dosage form of any one of claims 25 - 37 .

55 . The method of claim 53 wherein the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder, mood disorder, bipolar disorder, schizophrenia, schizoaffective disorder, mania in mood disorder, depression in mood disorder, treatment-refractory obsessive compulsive disorder, neurological dysfunction associated with Lesch-Nyhan syndrome, agitation associated with Alzheimer's disease, Fragile X syndrome or Fragile X-associated tremor-ataxia syndrome, autism spectrum disorder, Rett syndrome, or chorea-acanthocytosis.

56 . The method of claim 54 , wherein the hyperkinetic movement disorder is tardive dyskinesia.

57 . The method of claim 54 , wherein the hyperkinetic movement disorder is Tourette's syndrome.

58 . The method of claim 54 , wherein the hyperkinetic movement disorder is Huntington's disease.

59 . The method of claim 54 , wherein the hyperkinetic movement disorder is tics.

60 . The method of claim 54 , wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease.

61 . The method of claim 54 , wherein the hyperkinetic movement disorder is ataxia, chorea, dystonia, Huntington's disease, hemifacial spasm, myoclonus, restless leg syndrome, or tremors.

62 . The method of claim 54 , wherein the patient has been determined to have 22q11.2 deletion syndrome.

63 . The method of claim 54 , wherein the patient is predisposed to developing a psychiatric disorder due to the patient having 22q11.2 deletion syndrome.

64 . The method of claim 54 , wherein the patient has been determined to have COMT haploinsufficiency.

65 . The method of claim 54 , wherein the patient is predisposed to developing a psychiatric disorder due to the subject having COMT haploinsufficiency.

66 . The method of any one of claims 53 - 65 , wherein valbenazine or pharmaceutically acceptable salt thereof is administered to the patient for a first period of time followed by a second period of time, and wherein valbenazine or pharmaceutically acceptable salt is administered at a lower level during the first period of time than the second period of time.

67 . The method of claim 66 , wherein valbenazine or pharmaceutically acceptable salt thereof is administered during the first period of time in a daily unit dosage form comprising valbenazine or pharmaceutically acceptable salt at a level of about 40 mg as measured as the free base.

68 . The method of any one of claims 66 - 67 , wherein valbenazine or pharmaceutically acceptable salt thereof is administered during the second period of time in daily unit dosage form comprising valbenazine or a pharmaceutically acceptable salt at a level of about 80 mg as measured as the free base.

69 . The method of any one of claims 66 - 68 , wherein the first period of time is days, weeks or months.

70 . The method of any one of claims 66 - 69 , wherein the first period of time is one week.

71 . A kit comprising a plurality of the oral dosage product of claim 24 or the unit dosage form of any one of claims 25 - 37 in combination with instructions for administration.

72 . A method for producing a unit dosage form of valbenazine ditosylate comprising the steps of FIG. 1 .

73 . A composition comprising:

valbenazine, or a pharmaceutically acceptable salt thereof,

silicified microcrystalline cellulose;

isomalt;

hydroxypropyl methylcellulose;

partially pregelatinized maize starch; and

magnesium stearate.

74 . A solid composition of valbenazine, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, wherein the solid composition has a bulk density of at least about 0.5 mg/mL.

75 . A solid composition of valbenazine, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, wherein the solid composition has a tapped density of at least about 0.6 mg/mL.

76 . A solid composition of valbenazine, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, wherein the solid composition has a d(0.9) particle size distribution less than 100 m.

77 . A solid composition of valbenazine, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, wherein the solid composition has a blend uniformity between about 90% and about 110% with a relative standard deviation of the blend uniformity of less than about 2%.

78 . The solid composition of claim 77 , wherein the solid composition has a blend uniformity between about 95% and about 105% with a relative standard deviation of the blend uniformity of less than about 2%.

79 . A solid composition of valbenazine, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, wherein the solid composition has a blend uniformity between about 90% and about 110% with a standard deviation of the blend uniformity of less than about 2%.

80 . The solid composition of claim 79 , wherein the solid composition has a blend uniformity between about 95% and about 105% with a standard deviation of the blend uniformity of less than about 2%.

81 . The solid composition of any one of claims 74 - 80 , wherein the valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level ranging from about 20-160 mg as measured as the free base.

82 . The solid composition of claim 81 , wherein the valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 20 mg as measured as the free base.

83 . The solid composition of claim 81 , wherein the valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 40 mg as measured as the free base.

84 . The solid composition of claim 81 , wherein the valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 60 mg as measured as the free base.

85 . The solid composition of claim 81 , wherein the valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 80 mg as measured as the free base.

86 . The solid composition of claim 81 , wherein the valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 120 mg as measured as the free base.

87 . The solid composition of claim 81 , wherein the valbenazine, or a pharmaceutically acceptable salt thereof, is present at a level of about 160 mg as measured as the free base.

88 . The solid composition of any one of claims 74 - 87 , wherein the solid composition comprises valbenazine, or a pharmaceutically acceptable salt thereof, as measured by the free base, at a level of at least about 35% w/w.

89 . The solid composition of claim 88 , wherein the solid composition comprises valbenazine, or a pharmaceutically acceptable salt thereof, as measured by the free base, at a level of at least about 38% w/w.

90 . The solid composition of claim 88 , wherein the solid composition comprises valbenazine, or a pharmaceutically acceptable salt thereof, as measured by the free base, at a level of at least about 40% w/w.

91 . The solid composition of claim 88 , wherein the solid composition comprises valbenazine, or a pharmaceutically acceptable salt thereof, as measured by the free base, at a level of at least about 45% w/w.

92 . The solid composition of claim 88 , wherein the solid composition comprises valbenazine, or a pharmaceutically acceptable salt thereof, as measured by the free base, at a level of about 40% w/w.

93 . The solid composition of any one of claims 74 - 92 , wherein the pharmaceutically acceptable salt of valbenazine is a tosylate salt.

94 . The solid composition of claim 93 , wherein the pharmaceutically acceptable salt of valbenazine is valbenazine ditosylate.

95 . The solid composition of any of claims 74 - 94 , wherein the solid composition comprises granules of the valbenazine, or a pharmaceutically acceptable salt thereof, and the at least one pharmaceutically acceptable excipient.

96 . The solid composition of claim 95 , wherein the granules are prepared by dry granulation.

97 . The solid composition of claim 96 , wherein the granules are prepared by roller compaction.

98 . The solid composition of any of claims 95 - 97 , wherein the solid composition comprises a blend of the granules of valbenazine, or a pharmaceutically acceptable salt thereof, and the at least one pharmaceutically acceptable excipient with at least one lubricant.

99 . The solid composition of any of claims 74 - 98 , wherein the at least one pharmaceutically acceptable excipient is at least one lubricant.

100 . The solid composition of claim 99 , wherein the solid composition comprises at least one lubricant in an amount of between about 0.25% and about 5% w/w.

101 . The solid composition of claim 99 or 100 , wherein the at least one lubricant is chosen from magnesium stearate, calcium stearate, stearic acid, talc, starch, and fumed silica (silicon dioxide).

102 . The solid composition of claim 101 , wherein the at least one lubricant is magnesium stearate.

103 . The solid composition of any of claims 74 - 102 , wherein the at least one pharmaceutically acceptable excipient is at least one disintegrant.

104 . The solid composition of claim 103 , wherein the at least one disintegrant is present in an amount of between about 1% and about 10% w/w.

105 . The solid composition of claim 103 or 104 , wherein the at least one disintegrant is chosen from starch, alginic acid, sodium starch glycolate, croscarmellose, crospovidone, cellulose, and acid-carbonate effervescent systems.

106 . The solid composition of claim 105 , wherein the at least one disintegrant is starch.

107 . The solid composition of any of claims 74 - 106 , wherein the at least one pharmaceutically acceptable excipient is at least one binder.

108 . The solid composition of claim 107 , wherein the at least binder is present in an amount of between about 0.5% and about 5% w/w.

109 . The solid composition of claim 107 or 108 , wherein the at least one binder is chosen from hypromellose, polyvinylpyrrolidone, natural gums (e.g. acacia gum), microcrystalline cellulose, methylcellulose, ethylcellulose, sucrose, starch, and gelatin.

110 . The solid composition of claim 109 , wherein the at least one binder is hypromellose.

111 . The solid composition of any of claims 74 - 110 , wherein the at least one pharmaceutically acceptable excipient is at least one water soluble diluent.

112 . The solid composition of claim 111 , wherein the at least one water soluble diluent is present in an amount of between about 20% and about 95% w/w.

113 . The solid composition of claim 111 or 112 , wherein the at least one water soluble diluent is chosen from lactose, mannitol, isomalt, sucrose, dextrose, and sorbitol.

114 . The solid composition of claim 113 , wherein the at least one water soluble diluent is isomalt.

115 . The solid composition of any of claims 74 - 114 , wherein the at least one pharmaceutically acceptable excipient is at least one water insoluble filler.

116 . The solid composition of claim 115 , wherein the at least one insoluble filler is present in an amount of between about 20% and about 95% w/w.

117 . The solid composition of claim 114 or 115 , wherein the at least one water soluble filler is chosen from microcrystalline cellulose, starch, dicalcium phosphate dihydrate, and calcium carbonate.

118 . The solid composition of claim 116 , wherein the at least one water soluble filler is microcrystalline cellulose.

119 . A solid pharmaceutical composition comprising:

valbenazine, or a pharmaceutically acceptable salt thereof,

at least one water insoluble filler;

at least one water soluble diluent;

at least one binder;

at least one disintegrant; and

at least one lubricant.

120 . The solid pharmaceutical composition of claim 119 , wherein the pharmaceutically acceptable salt of valbenazine is a tosylate salt.

121 . The solid pharmaceutical composition of claim 120 , wherein the pharmaceutically acceptable salt of valbenazine is valbenazine tosylate.

122 . The solid pharmaceutical composition of any one of claims 119 - 121 , wherein the solid pharmaceutical composition has a bulk density of at least about 0.5 mg/mL.

123 . The solid pharmaceutical composition of any one of claims 119 - 122 , wherein the solid pharmaceutical composition has a tapped density of at least about 0.6 mg/mL.

124 . The solid pharmaceutical composition of any one of claims 119 - 123 , wherein the solid pharmaceutical composition has a d(0.9) particle size distribution less than 100 μm.

125 . The solid pharmaceutical composition of any one of claims 119 - 124 , wherein the solid pharmaceutical composition has a blend uniformity between about 90% and about 110% with a relative standard deviation of the blend uniformity of less than about 2%.

126 . The solid pharmaceutical composition of claim 125 , wherein the solid pharmaceutical composition has a blend uniformity between about 95% and about 105% with a relative standard deviation of the blend uniformity of less than about 2%.

127 . The solid pharmaceutical composition of any one of claims 119 - 124 , wherein the solid pharmaceutical composition has a blend uniformity between about 90% and about 110% with a standard deviation of the blend uniformity of less than about 2%.

128 . The solid composition of claim 127 , wherein the solid pharmaceutical composition has a blend uniformity between about 95% and about 105% with a standard deviation of the blend uniformity of less than about 2%.

129 . An oral dosage product comprising the composition of any one of claims 74 - 128 .

130 . A unit dosage form comprising the solid composition of any one of claims 74 - 128 .

131 . A unit dosage form of a pharmaceutical composition comprising:

valbenazine ditosylate having a w/w % of about 40%;

at least one water insoluble filler having a w/w % of about 25%;

at least one water soluble diluent having a w/w % of about 20%;

at least one binder having a w/w % of about 5%;

at least one disintegrant having a w/w % of about 7.5%; and

at least one lubricant having a w/w % of about 2.5%.

132 . The unit dosage form of claim 130 or 131 , comprising a capsule of size 1 or smaller and at least 80 mg of valbenazine, or a pharmaceutically acceptable salt thereof, as measured as the free base.

133 . The unit dosage form of claim 130 or 131 , comprising a capsule of size 2 or smaller.

134 . The unit dosage form of claim 130 or 131 , comprising a capsule of size 2 or smaller and at least 20 mg of valbenazine, or a pharmaceutically acceptable salt thereof, as measured as the free base.

135 . The unit dosage form of claim 130 or 131 , comprising at least 40 mg valbenazine, or a pharmaceutically acceptable salt thereof, as measured as the free base.

136 . The unit dosage form of claim 130 or 131 , comprising a capsule of size 0 or smaller and at least 120 mg of valbenazine, or a pharmaceutically acceptable salt thereof, as measured as the free base.

137 . The unit dosage form of any one of claim 130 - 136 , having an average stratified content uniformity of between about 99% and about 100% with a standard deviation of the mean of less than about 3.5%.

138 . The unit dosage form of any one of claim 130 - 136 , having an average stratified content uniformity of between about 99% and about 100% with a standard error of the mean of less than about 3.5%.

139 . The unit dosage form of any one of claim 130 - 138 , having a dissolution profile of at least 80% dissolution at 30 minutes in a USP Paddle Dissolution Method 2 apparatus and 0.1 N HCl medium.

140 . The unit dosage form of any one of claims 130 - 139 , wherein the pharmaceutically acceptable salt of valbenazine is a tosylate salt.

141 . The unit dosage form of claim 140 , wherein the pharmaceutically acceptable salt of valbenazine is valbenazine tosylate.

142 . A process for preparing a solid composition of valbenazine, or a pharmaceutically acceptable salt thereof, wherein the process comprises:

a) subjecting a blend of valbenazine, or a pharmaceutically acceptable salt thereof, at least one water insoluble filler, and at least one water soluble diluent to comminution;

b) blending the product of step a) with at least one binder and at least one disintegrant;

c) determining the blend uniformity of the product of step b); and

d) blending the product of step b) with at least one lubricant only if the blend uniformity satisfies a predetermined criteria to produce a solid composition of valbenazine, or a pharmaceutically acceptable salt thereof.

143 . The process of claim 142 , further comprising,

e) determining density and/or particle size distribution of the product of step d); and

f) subjecting the product of step d) to dry granulation to produce granules of valbenazine, or a pharmaceutically acceptable salt thereof, only if the density and/or particle size distribution satisfies a predetermined criteria.

144 . The process of claim 143 , further comprising,

g) determining density and/or particle size distribution of the product of step f); and

h) blending the granules of step f) with at least one lubricant only if the density and/or particle size distribution satisfies a predetermined criteria.

145 . The process of claim 144 , further comprising,

i) determining density and/or blend uniformity of the product of step h);

j) encapsulating the product of step h) to produce a unit dosage form comprising valbenazine, or a pharmaceutically acceptable salt thereof, only if the density and/or blend uniformity satisfies a predetermined criteria.

146 . The process of claim 145 , further comprising determining the disintegration and/or content uniformity of the unit dosage form.

147 . A unit dosage form prepared by the process of claim 146 .

148 . A process for preparing a unit dosage form comprising valbenazine, or a pharmaceutically acceptable salt thereof, wherein the process comprises:

encapsulating the solid composition of any one of claims 74 - 128 , to produce the unit dosage form comprising valbenazine, or a pharmaceutically acceptable salt thereof.

149 . A unit dosage form comprising valbenazine, or a pharmaceutically acceptable salt thereof, prepared by the process of claim 148 .

150 . A process for preparing a unit dosage form comprising valbenazine, or a pharmaceutically acceptable salt thereof, wherein the process comprises:

encapsulating a lubricated blend to produce a solid composition comprising valbenazine, or a pharmaceutically acceptable salt thereof,

wherein the lubricated blend comprises granules of valbenazine, or a pharmaceutically acceptable salt thereof, and at least one lubricant.

151 . The process of claim 150 , wherein the lubricated blend is prepared by a process comprising the steps of: blending at least one lubricant with granules of valbenazine, or a pharmaceutically acceptable salt thereof, to produce a lubricated blend.

152 . The process of claim 151 , wherein the granules of valbenazine, or a pharmaceutically acceptable salt thereof, is prepared by a process comprising the steps of: dry granulating a blend to produce granules of valbenazine, or a pharmaceutically acceptable salt thereof.

153 . The process of claim 152 , wherein dry granulating a blend comprises gravity feeding the blend through the roller compactor.

154 . The process of claim 152 or 153 , wherein the blend is prepared by a process comprising the steps of: blending at least one lubricant with an intragranular blend to produce the blend.

155 . The process of claim 154 , wherein the intragranular blend is prepared by a process comprising blending a pre-blend with at least one disintegrant and at least one binder to produce the intragranular blend.

156 . The process of claim 155 , wherein the pre-blend is prepared by a process comprising the steps of: blending valbenazine, or a pharmaceutically acceptable salt thereof, with at least one water-insoluble filler and at least one water soluble diluent to produce the pre-blend.

157 . A unit dosage form comprising valbenazine, or a pharmaceutically acceptable salt thereof, prepared by the process of claim 150 .

158 . A process for preparing a unit dosage form comprising valbenazine, or a pharmaceutically acceptable salt thereof, wherein the process comprises:

preparing a dispersion of valbenazine, or a pharmaceutically acceptable salt thereof, in at least one water-insoluble filler and at least one water soluble diluent to produce a pre-blend;

blending the pre-blend with one or more excipients to produce a blend;

granulating the blend to produce a granulated blend;

optionally blending the granulated blend with one or more excipients to produce a lubricated blend; and

encapsulating the lubricated blend.

159 . A unit dosage form comprising valbenazine, or a pharmaceutically acceptable salt thereof, prepared by the process of claim 158 .

160 . A method comprising orally administering a unit dosage form of the solid composition of any one of claims 74 - 118 , or a solid pharmaceutical composition of any one of claims 119 - 128 , or a unit dosage form of any one of claims 130 - 141 , 147 , 149 , 157 , or 159 to a patient in need thereof.

161 . The method of claim 160 , wherein the unit dosage form of the solid composition is administered to the patient to treat a neurological or psychiatric disease or disorder.

162 . The method of claim 161 , wherein the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder, mood disorder, bipolar disorder, schizophrenia, schizoaffective disorder, mania in mood disorder, depression in mood disorder, treatment-refractory obsessive compulsive disorder, neurological dysfunction associated with Lesch-Nyhan syndrome, agitation associated with Alzheimer's disease, Fragile X syndrome or Fragile X-associated tremor-ataxia syndrome, autism spectrum disorder, Rett syndrome, or chorea-acanthocytosis.

163 . The method of claim 162 , wherein the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder.

164 . The method of claim 163 , wherein the hyperkinetic movement disorder is tardive dyskinesia.

165 . The method of claim 163 , wherein the hyperkinetic movement disorder is Tourette's syndrome.

166 . The method of claim 163 , wherein hyperkinetic movement disorder is Huntington's disease.

167 . The method of claim 163 , wherein hyperkinetic movement disorder is tics.

168 . The method of claim 163 , wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease.

169 . The method of claim 163 , wherein the hyperkinetic movement disorder is ataxia, chorea, dystonia, Huntington's disease, myoclonus, restless leg syndrome, or tremors.

170 . The method of any one of claims 160 - 169 , wherein the patient has been determined to have 22q11.2 deletion syndrome.

171 . The method of any one of claims 160 - 169 , wherein, the patient is predisposed to developing a psychiatric disorder due to the patient having 22q11.2 deletion syndrome.

172 . The method of any one of claims 160 - 169 , wherein the patient has been determined to have COMT haploinsufficiency.

173 . The method of any one of claims 160 - 169 , wherein the patient is predisposed to developing a psychiatric disorder due to the patient having COMT haploinsufficiency.

174 . A kit comprising a plurality of oral unit dosage forms of any one of the claims 130 - 141 , 147 , 149 , 157 , or 159 , in combination with instructions for administration.

175 . A unit dosage form of any one of claims 130 - 141 , 147 , 149 , 157 , or 159 , for use in a method of treating a neurological or psychiatric disease or disorder of a patient in need thereof.

176 . The unit dosage form of claim 175 , wherein the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder, mood disorder, bipolar disorder, schizophrenia, schizoaffective disorder, mania in mood disorder, depression in mood disorder, treatment-refractory obsessive compulsive disorder, neurological dysfunction associated with Lesch-Nyhan syndrome, agitation associated with Alzheimer's disease, Fragile X syndrome or Fragile X-associated tremor-ataxia syndrome, autism spectrum disorder, Rett syndrome, or chorea-acanthocytosis.

177 . The unit dosage form of claim 176 , wherein the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder.

178 . The unit dosage form of claim 177 , wherein the hyperkinetic movement disorder is tardive dyskinesia.

179 . The unit dosage form of claim 177 , wherein the hyperkinetic movement disorder is Tourette's syndrome.

180 . The unit dosage form of claim 177 , wherein hyperkinetic movement disorder is Huntington's disease.

181 . The unit dosage form of claim 177 , wherein hyperkinetic movement disorder is tics.

182 . The unit dosage form of claim 177 , wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease.

183 . The unit dosage form of claim 177 , wherein the hyperkinetic movement disorder is ataxia, chorea, dystonia, Huntington's disease, myoclonus, restless leg syndrome, or tremors.

184 . The unit dosage form of any one of claims 175 - 183 , wherein the patient has been determined to have 22q11.2 deletion syndrome.

185 . The unit dosage form of any one of claims 175 - 183 , wherein, the patient is predisposed to developing a psychiatric disorder due to the patient having 22q11.2 deletion syndrome.

186 . The unit dosage form of any one of claims 175 - 183 , wherein the patient has been determined to have COMT haploinsufficiency.

187 . The unit dosage form of any one of claims 175 - 183 , wherein the patient is predisposed to developing a psychiatric disorder due to the patient having COMT haploinsufficiency.