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

Abstract

Solid pharmaceutical compositions with high drug loading are provided. A formulation useful for the solid pharmaceutical composition includes valbenazine, or a pharmaceutically acceptable salt thereof, silicified microcrystalline cellulose, isomalt, hydroxypropyl methylcellulose, partially pregelatinized maize starch, and magnesium stearate.

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.