US2018296479A1PendingUtilityA1
Rapidly Dispersible Dosage Form with High Drug Content
Assignee: Aprecia Pharmaceuticals LLCPriority: Mar 15, 2013Filed: Jun 22, 2018Published: Oct 18, 2018
Est. expiryMar 15, 2033(~6.7 yrs left)· nominal 20-yr term from priority
A61K 9/1623A61K 9/2054A61K 9/1652A61K 9/1617B29K 2105/0035B33Y 10/00A61P 25/08A61K 9/2027A61K 9/7007B29K 2105/0058A61K 9/1611A61K 9/2009A61K 9/2013A61K 9/2018B33Y 80/00A61K 9/0056B29C 64/165B29K 2105/251A61K 9/1635A61K 31/55A61K 9/2095A61K 9/1694A61K 9/2077B33Y 70/00
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Claims
Abstract
A high dose orodispersible dosage form of oxcarbazepine is provided. Drug-containing particles of oxcarbazepine are included within a porous bound matrix. The dosage form disperses in saliva or water in less than 15 sec and it has sufficient hardness to withstand handling and storage. It can be used to treat diseases or disorders that are therapeutically responsive to oxcarbazepine or a derivative thereof.
Claims
exact text as granted — not AI-modified1 ) A rapidly dispersible solid dosage form comprising a porous non-compressed three-dimensionally printed bound matrix comprising:
drug-containing particles having an effective particle size and comprising a first grade of oxcarbazepine (OXC) particles having a first native particle size, a second grade of OXC particles having a second native particle size, at least one disintegrant, at least one surfactant, and at least one binder; at least one disintegrant; and at least one binder; wherein the dosage form disperses in 15 sec or less when placed in 15 ml of aqueous fluid; and the ratio of effective particle size to first native particle size is >1:1 to 5:1, and the ratio of effective particle size to second native particle size is 20:1 to 50:1.
2 ) A rapidly dispersible three-dimensionally printed porous non-compressed bound matrix comprising:
a first grade of OXC particles having a first native particle size, a second grade of OXC particles having a second native particle size, at least one sweetener, at least one binder, at least one disintegrant, at least one surfactant, and at least one glidant; wherein the matrix comprises particles bound by binder; the matrix disperses in less than 15 sec in a volume of 15 ml of aqueous fluid; the OXC particles are included in drug-containing particles having an effective particle size and comprising the OXC particles and at least one pharmaceutical excipient as carrier; the content of OXC in the matrix ranges from 35-60% wt based upon the total weight of the matrix; and the ratio of effective particle size to first native particle size is >1:1 to 5:1, and the ratio of effective particle size to second native particle size is 20:1 to 50:1.
3 ) The dosage form of claim 1 , wherein: a) OXC particles possess a bi-modal or multi-modal particle size distribution; b) the drug-containing particles possess a mono-modal, bi-modal or multi-modal particle size distribution; or c) a combination of one or more of the above.
4 ) The dosage form of claim 1 , wherein: a) the at least one surfactant is present in an amount ranging from 0.5-7.0% wt based upon the final weight of the dosage form; b) the at least one sweetener is present in an amount ranging from 0.01-2.0% based upon the final weight of the dosage form; c) the at least one binder is present in an amount ranging from 5-15% based upon the final weight of the dosage form; d) the at least one disintegrant is present in an amount ranging from 10-30% based upon the final weight of the dosage form; and/or e) the at least one glidant is present in an amount ranging from 0-2% based upon the final weight of the dosage form.
5 ) The dosage form of claim 1 , wherein: a) the hardness of the matrix ranges from about 1 to about 7 kiloponds (kp), about 1 to about 3 kp; b) the matrix disperses in 10 sec or less when placed in 15 ml of water or in saliva; c) binder is introduced into the matrix by way of printing fluid used to form the matrix; d) binder is introduced into the matrix by way of bulk powder used to form the matrix; e) the matrix comprises about 150 mg to about 600 mg of OXC; and/or f) the matrix comprises 10 to 40 three-dimensionally printed incremental layers.
6 ) The dosage form of claim 1 , wherein the drug-containing particles further comprise sweetener and/or flavorant.
7 ) The dosage form of claim 1 , wherein: a) the content of drug-containing particles in the matrix generally ranges from 55-85% wt, 60-80% wt or 65-70% wt based upon the total weight of matrix in the final dosage form; b) the content of native particles of OXC in the drug-containing particles ranges from 55-85% wt, 60-80% wt or 65-70% wt, based upon the final weight of the drug-containing particles; c) the content of disintegrant in the drug-containing particles ranges from 0-30%, 1-15%, or 2-5% wt, based upon the final weight of the drug-containing particles; d) the content of binder in the drug-containing particles ranges from 0-10%, 1-7%, or 2-5% wt, based upon the final weight of the drug-containing particles; e) the content of surfactant in the drug-containing particles ranges from 0-10%, 1-5%, or 1.4-4.2% wt, based upon the final weight of the drug-containing particles; and/or f) the drug-containing particles are manufactured by wet granulation.
8 ) The dosage form of claim 1 , wherein the matrix comprises about 150 to about 1200 mg, about 150 mg, about 300 mg, about 450 mg, about 600 mg, about 750 mg, about 900 mg, about 1050 mg or about 1200 of OXC.
9 ) The dosage form of claim 1 , wherein the dosage form has been prepared by a three-dimensional printing process employing printing fluid, drug-containing particles and bulk powder of the following compositions:
Printing fluid
Water (% wt)
80-95 or
80-90
Glycerin (% wt)
0.5-20 or
2-7
Alcohol (% wt)
0.1-20 or
1-10
Surfactant (% wt)
0.01-10 or
1-5
Sweetener (% wt)
0-10 or
1-5
Binder (% wt)
0-10
OXC Drug-containing particles:
OXC (% wt)
55-75 or
60-70
Disintegrant (% wt)
15-45 or
30-40
Binder (% wt)
0-10 or
2-5
Surfactant (% wt)
0-10 or
1-5
Bulk powder:
OXC containing particles (% wt)
55-65 or
55-65
Disintegrant (% wt)
2-15 or
3-12
Binder (% wt)
20-45 or
20-35
Glidant (% wt)
0.1-1.5 or
0.2-0.7.
10 ) The dosage form of claim 1 , wherein the dosage form has the following composition:
Oxcarbazepine (% wt)
30-40
35-45
Disintegrant (% wt)
15-30
15-25
Binder (% wt)
30-55
30-50
Glidant (% wt)
0-5
>0-5
Glycerin (% wt)
>0-20
>0-5
Surfactant (% wt)
0-5
>0-5
Sweetener (% wt)
0-5
>0-5
11 ) The dosage form of claim 1 , wherein the dosage form is shaped as a wafer, cylinder, ring, donut, tube, cube, spheroid, ellipsoid or rectangular box.
12 ) The dosage form of claim 1 , wherein: a) the binder is selected from the group consisting of polyvinylpyrrolidone (povidone), mannitol, hydroxypropylcellulose, and a combination thereof; b) the disintegrant is selected from the group consisting of microcrystalline cellulose, a combination of two grades of microcrystalline cellulose, croscarmellose, and a combination thereof; orb) a combination of the above.
13 ) A method of treating a disease, condition or disorder that is therapeutically responsive to oxcarbazepine comprising administering the dosage form of claim 1 one to three times daily to a subject in need thereof throughout a treatment period.
14 ) The dosage form of claim 5 , wherein the thickness (height) of an incremental layer ranges from 0.006 to 0.014 inches or 0.008 to 0.012 inches.
15 ) A rapidly dispersible porous non-compressed three-dimensionally printed bound matrix comprising:
drug-containing particles comprising at least one disintegrant, at least one binder, at least one surfactant and native particles of drug, wherein the drug-containing particles have an effective particle size and the native particles of drug have a native particle size, and the ratio of effective particle size to native particle size ranges from greater than 1:1 to 200:1; at least one disintegrant; and at least one binder; wherein the hardness of the matrix ranges from about 1 to about 7 kiloponds.
16 ) The matrix of claim 15 , wherein the matrix disperses in 15 sec or less when placed in 15 ml of aqueous fluid.
17 ) The matrix of any one of the above claims, wherein the average native particle size is such that 90%-100% of the drug is <10 microns, and the ratio of effective particle size to native particle size is in the range of 10:1 to 200:1.
18 ) The matrix of any one of the above claims, wherein the average native particle size is such that not more than 20% of the drug is <32 microns, 40-70% of the drug is <63 microns, 70-95% of the drug is <125 microns, and 100% of the drug is <250 microns, and the ratio of effective particle size to native particle size is in the range of >1:1 to about 10:1.
19 ) The matrix of any one of the above claims, wherein the native particles of drug have an average, mean or median native particle size in the range of about 1 to about 90 microns, about 1 to about 75 microns, about 1 to about 50 microns, about 1 to about 30 microns, about 1 to about 15 microns, about 1 to about 10 microns, about 2 to about 14 microns, about 10 to about 80 microns, about 20 to about 70 microns, about 20 to about 60 microns or about 30 to about 50 microns.
20 ) The matrix of any one of the above claims, wherein the drug-containing particles have an average, mean or median effective particle size in the range of about 50 to about 400 microns, about 50 to about 300 microns, about 50 to about 250 microns, about 60 to about 250 microns, about 60 to about 100 microns, or about 75 to about 250 microns.
21 ) The matrix of any one of the above claims, wherein the drug is a poorly water soluble.
22 ) The matrix of claim 21 , wherein the drug is OXC.
23 ) The matrix of claim 15 , comprising:
drug-containing particles comprising at least one disintegrant, at least one binder, at least one surfactant, a first grade of native particles of drug and a second grade of native particles of drug, wherein the drug-containing particles have an effective particle size and the first grade of native particles of drug have a first native particle size and the second grade of native particles of drug have a second native particle size, and the ratio of effective particle size to first native particle size ranges from greater than 1:1 to about 5:1, and the ratio of effective particle size to second native particle size ranges from about 20:1 to about 50:1; at least one disintegrant; and at least one binder; wherein the hardness of the matrix ranges from about 1 to about 7 kiloponds.
24 ) The matrix of any one of the above claims, wherein:
the drug-containing particles further comprise at least one sweetener and at least one glidant; the matrix comprises particles bound by binder; the matrix disperses in less than 15 sec in a volume of 15 ml of aqueous fluid; and/or the content of drug in the matrix ranges from 35-60% wt based upon the total weight of the matrix.
25 ) The matrix of claim 24 , wherein: a) the at least one surfactant is present in an amount ranging from 0.5-7.0% wt based upon the final weight of the dosage form; b) the at least one sweetener is present in an amount ranging from 0.01-2.0% based upon the final weight of the dosage form; c) the at least one binder is present in an amount ranging from 5-15% based upon the final weight of the dosage form; d) the at least one disintegrant is present in an amount ranging from 10-30% based upon the final weight of the dosage form; and/or e) the at least one glidant is present in an amount ranging from 0-2% based upon the final weight of the dosage form.
26 ) The matrix any one of the above claims, wherein: a) the native particles of drug possess a bi-modal or multi-modal particle size distribution; b) the drug-containing particles possess a mono-modal, bi-modal or multi-modal particle size distribution; or c) a combination of one or more of the above.
27 ) The matrix any one of the above claims, wherein: a) the hardness ranges from about 1 to about 3 kp; b) the matrix disperses in 10 sec or less when placed in 15 ml of water or in saliva; c) the at least one binder is introduced into the matrix by way of printing fluid used to form the matrix; d) the at least one binder is introduced into the matrix by way of bulk powder used to form the matrix; e) the matrix comprises about 150 mg to about 600 mg of drug; and/or f) the matrix comprises 10 to 40 three-dimensionally printed incremental layers.
28 ) The matrix any one of the above claims, wherein the drug-containing particles further comprise sweetener and/or flavorant.
29 ) The matrix any one of the above claims, wherein: a) the content of drug-containing particles in the matrix generally ranges from 55-85% wt, 60-80% wt or 65-70% wt based upon the total weight of matrix in the final dosage form; b) the content of native particles of OXC in the drug-containing particles ranges from 55-85% wt, 60-80% wt or 65-70% wt, based upon the final weight of the drug-containing particles; c) the content of disintegrant in the drug-containing particles ranges from 0-30%, 1-15%, or 2-5 wt, based upon the final weight of the drug-containing particles; d) the content of binder in the drug-containing particles ranges from 0-10%, 1-7%, or 2-5% wt, based upon the final weight of the drug-containing particles; e) the content of surfactant in the drug-containing particles ranges from 0-10%, 1-5%, or 1.4-4.2% wt, based upon the final weight of the drug-containing particles; and/or f) the drug-containing particles are manufactured by wet granulation.
30 ) The matrix any one of the above claims, wherein the matrix comprises about 150 to about 1200 mg, about 150 mg, about 300 mg, about 450 mg, about 600 mg, about 750 mg, about 900 mg, about 1050 mg or about 1200 of drug.
31 ) The matrix any one of the above claims, wherein the matrix has been prepared by a three-dimensional printing process employing printing fluid, drug-containing particles and bulk powder of the following compositions:
printing fluid comprising glycerin; drug-containing particles comprising a first grade of drug native particles, at least one first disintegrant, at least one first binder and at least one first surfactant; and bulk powder comprising the drug-containing particles, at least one second disintegrant, at least one second binder and at least one glidant.
32 ) The matrix of claim 31 , wherein the printing fluid comprises glycerin and alcohol or alcohol.
33 ) The matrix of claim 31 , wherein the bulk powder comprises the drug-containing particles, at least one second disintegrant, at least one second binder and at least one glidant.
34 ) The matrix of claim 31 , wherein:
printing fluid comprises water, glycerin, alcohol and surfactant; drug-containing particles comprising a first grade of drug native particles, at least one first disintegrant, at least one first binder and at least one first surfactant; and bulk powder comprising the drug-containing particles, at least one second disintegrant, at least one second binder and at least one glidant.
35 ) The matrix of claim 31 , wherein the matrix has been prepared by a three-dimensional printing process employing printing fluid, drug-containing particles and bulk powder of the following compositions:
Printing fluid
Water (% wt)
80-95 or
80-90
Glycerin (% wt)
0.5-20 or
2-7
Alcohol (% wt)
0.1-20 or
1-10
Surfactant (% wt)
0.01-10 or
1-5
Sweetener (% wt)
0-10 or
1-5
Binder (% wt)
0-10
OXC Drug-containing particles:
OXC (% wt)
55-75 or
60-70
Disintegrant (% wt)
15-45 or
30-40
Binder (% wt)
0-10 or
2-5
Surfactant (% wt)
0-10 or
1-5
Bulk powder:
OXC containing particles (% wt)
55-65 or
55-65
Disintegrant (% wt)
2-15 or
3-12
Binder (% wt)
20-45 or
20-35
Glidant (% wt)
0.1-1.5 or
0.2-0.7.
36 ) The matrix of any one of the above claims, wherein the matrix is shaped as a wafer, cylinder, ring, donut, tube, cube, spheroid, ellipsoid or rectangular box.
37 ) The matrix of any one of the above claims, wherein: a) the binder is selected from the group consisting of polyvinylpyrrolidone (povidone), mannitol, hydroxypropylcellulose, and a combination thereof; b) the disintegrant is selected from the group consisting of microcrystalline cellulose, a combination of two grades of microcrystalline cellulose, croscarmellose, and a combination thereof; or b) a combination of the above.
38 ) A method of treating a disease, condition or disorder that is therapeutically responsive to the drug comprising administering the matrix of any one of the above claims one or more times daily to a subject in need thereof throughout a treatment period.
39 ) The matrix of any one of the above claims, wherein the thickness (height) of an incremental layer ranges from 0.006 to 0.014 inches or 0.008 to 0.012 inches.
40 ) A three-dimensionally printed bound matrix comprising:
drug-containing particles comprising at least one first binder and native particles of drug, wherein the drug-containing particles have an effective particle size and the native particles of drug have a native particle size, and the ratio of effective particle size to native particle size ranges from greater than 1:1 to 200:1.
41 ) The matrix of claim 40 , wherein:
the drug-containing particles comprise at least one first binder, a first grade of native particles of drug and a second grade of native particles of drug, wherein the first grade of native particles of drug have a first native particle size and the second grade of native particles of drug have a second native particle size, and the first native particle size is smaller than the second native particle size.
42 ) The matrix of claim 41 , wherein:
the drug-containing particles comprise at least one first binder, a first grade of native particles of drug and a second grade of native particles of drug, wherein the drug-containing particles have an effective particle size and the first grade of native particles of drug have a first native particle size and the second grade of native particles of drug have a second native particle size, and the ratio of effective particle size to first native particle size ranges from greater than 1:1 to about 5:1, and the ratio of effective particle size to second native particle size ranges from about 20:1 to about 200:1 or about 20:1 to about 50:1.
43 ) The matrix of claim 40 , 41 or 42 , wherein the bound matrix further comprises at least one second binder that binds the drug-containing particles to form the bound matrix.
44 ) The matrix of claim 40 - 42 or 43 , wherein the drug-containing particles further comprise at least one first disintegrant.
45 ) The matrix of claim 40 - 43 or 44 , wherein the bound matrix further comprises at least second disintegrant outside the drug-containing particles.
46 ) The matrix of any one of the above claims, wherein the drug-containing particles are prepared by wet granulation.
47 ) A rapidly dispersible porous non-compressed three-dimensionally printed bound matrix comprising:
drug-containing particles comprising at least one first disintegrant, at least one first binder, at least one surfactant and native particles of drug, wherein the drug-containing particles have an average, mean or median effective particle size and the native particles of drug have an average, mean or median native particle size, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, native particle size ranges from greater than 1:1 to 200:1; at least one second disintegrant; and at least one second binder; wherein the hardness of the matrix ranges from about 1 to about 7 kiloponds.
48 ) The matrix of claim 47 , wherein the matrix disperses in 15 sec or less when placed in 15 ml of aqueous fluid.
49 ) The matrix of claim 47 , wherein the average native particle size is such that 90%-100% wt of the drug is <10 microns, and the ratio of average effective particle size to average native particle size is in the range of 10:1 to 200:1.
50 ) The matrix of claim 47 , wherein the average native particle size is such that not more than 20% wt of the drug is <32 microns, 40-70% wt of the drug is <63 microns, 70-95% wt of the drug is <125 microns, and 100% wt of the drug is <250 microns, and the ratio of average effective particle size to average native particle size is in the range of greater than 1:1 to about 10:1.
51 ) The matrix of claim 47 , wherein the native particles of drug have an average, mean or median native particle size in the range of about 1 to about 90 microns, about 1 to about 75 microns, about 1 to about 50 microns, about 1 to about 30 microns, about 1 to about 15 microns, about 1 to about 10 microns, about 2 to about 14 microns, about 10 to about 80 microns, about 20 to about 70 microns, about 20 to about 60 microns or about 30 to about 50 microns.
52 ) The matrix of claim 47 , wherein the drug-containing particles have an average, mean or median effective particle size in the range of about 50 to about 400 microns, about 50 to about 300 microns, about 50 to about 250 microns, about 60 to about 250 microns, about 60 to about 100 microns, or about 75 to about 250 microns.
53 ) The matrix of claim 47 , wherein the drug is a poorly water soluble.
54 ) The matrix of claim 47 , comprising:
drug-containing particles comprising at least one first disintegrant, at least one first binder, at least one surfactant, a first grade of native particles of drug and a second grade of native particles of drug, wherein the drug-containing particles have an average, mean or median effective particle size and the first grade of native particles of drug have an average, mean or median first native particle size and the second grade of native particles of drug have an average, mean or median second native particle size, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, first native particle size ranges from greater than 1:1 to about 5:1, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, second native particle size ranges from about 20:1 to about 50:1; at least one second disintegrant; and at least one second binder; wherein the hardness of the matrix ranges from about 1 to about 7 kiloponds.
55 ) The matrix of claim 54 , wherein:
the drug-containing particles further comprise at least one sweetener and at least one glidant; the matrix comprises particles bound by said second binder; the matrix disperses in less than 15 sec in a volume of 15 ml of aqueous fluid; and/or the content of drug in the matrix is 35-60% wt based upon the total weight of the matrix.
56 ) The matrix of claim 55 , wherein: a) the at least one surfactant is present in an amount of 0.5-7.0% wt based upon the final weight of the dosage form; b) the at least one sweetener is present in an amount of 0.01-2.0% wt based upon the final weight of the dosage form; c) the at least one first binder and the at least one second binder are together present in an amount of 5-15% wt based upon the final weight of the dosage form; d) the at least one first disintegrant and the at least one second disintegrant are together present in an amount of 10-30% wt based upon the final weight of the dosage form; and/or e) the at least one glidant is present in an amount of 0-2% wt based upon the final weight of the dosage form.
57 ) The matrix of claim 47 , wherein: a) the native particles of drug possess a bi-modal or multi-modal particle size distribution; b) the drug-containing particles possess a mono-modal, bi-modal or multi-modal particle size distribution; or c) a combination of one or more of the above.
58 ) The matrix of claim 47 , wherein: a) the hardness ranges from about 1 to about 3 kp; b) the matrix disperses in 10 sec or less when placed in 15 ml of water or in saliva; c) the matrix comprises about 150 mg to about 600 mg of drug; and/or d) the matrix comprises 10 to 40 three-dimensionally printed incremental layers.
59 ) The matrix of claim 47 , wherein: a) the content of drug-containing particles in the matrix is 55-85% wt, 60-80% wt or 65-70% wt based upon the total weight of matrix in the final dosage form; b) the content of native particles of drug in the drug-containing particles is 55-85% wt, 60-80% wt or 65-70% wt, based upon the final weight of the drug-containing particles; c) the content of first disintegrant in the drug-containing particles ranges up to 30%, 1-15%, or 2-5% wt, based upon the final weight of the drug-containing particles; d) the content of first binder in the drug-containing particles ranges up to 10%, 1-7%, or 2-5% wt, based upon the final weight of the drug-containing particles; e) the content of surfactant in the drug-containing particles ranges up to 10%, 1-5%, or 1.4-4.2% wt, based upon the final weight of the drug-containing particles; and/or f) the drug-containing particles are manufactured by wet granulation.
60 ) The matrix of claim 47 , wherein the matrix comprises about 150 to about 1200 mg about 150 mg, about 300 mg, about 450 mg, about 600 mg, about 750 mg, about 900 mg, about 1050 mg or about 1200 of drug.
61 ) The matrix of claim 47 , wherein the matrix has been prepared by a three-dimensional printing process employing printing fluid, drug-containing particles and bulk powder of the following compositions:
printing fluid comprising glycerin; drug-containing particles comprising a first grade of drug native particles, the at least one first disintegrant, the at least one first binder and at least one first surfactant; and bulk powder comprising the drug-containing particles, the at least one second disintegrant, the at least one second binder and at least one glidant.
62 ) The matrix of claim 61 , wherein the printing fluid comprises: a) glycerin and alcohol; or b) alcohol.
63 ) The matrix of claim 31 , wherein:
the printing fluid comprises water, glycerin, alcohol and surfactant.
64 ) The matrix of claim 47 , wherein the matrix is shaped as a wafer, cylinder, ring, donut, tube, cube, spheroid, ellipsoid or rectangular box.
65 ) The matrix of claim 47 , wherein: a) the first binder and second binder are independently selected at each occurrence from the group consisting of polyvinylpyrrolidone, mannitol, hydroxypropylcellulose, and a combination thereof; b) the first disintegrant and the second disintegrant are independently selected at each occurrence from the group consisting of microcrystalline cellulose, a combination of two grades of microcrystalline cellulose, croscarmellose, and a combination thereof; or c) a combination of the above.
66 ) The matrix of claim 47 , wherein: a) the drug-containing particles comprise at least two first disintegrants and at least one binder; b) the matrix comprises at least two second binders and at least one second disintegrant; c) a combination of any of the above.
67 ) The matrix of claim 47 , wherein: a) at least one first binder is different than the at least one second binder; b) at least one first disintegrant is different than the at least one second disintegrant; c) at least one first binder is the same as the at least one second binder; d) at least one first disintegrant is the same as the at least one second disintegrant; or e) a combination of any of the above.
68 ) A method of preparing a rapidly dispersible porous three-dimensionally printed bound matrix, the method comprising:
forming drug-containing particles comprising at least one first disintegrant, at least one first binder, at least one surfactant and native particles of drug, wherein the drug-containing particles have an average, mean or median effective particle size and the native particles of drug have an average, mean or median native particle size, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, native particle size ranges from greater than 1:1 to 200:1; combining at least one second disintegrant and at least one second binder with said drug-containing particles to form a bulk powder; and three-dimensionally printing said bulk powder to form one or more of said three-dimensionally printed bound matrix.
69 ) The method of claim 68 , wherein the step of forming drug-containing particles comprises granulating the at least one first disintegrant, at least one first binder, at least one surfactant and native particles of drug.
70 ) The method of claim 68 or 69 , wherein the step of three-dimensionally printing comprises forming plural stacked incremental layers of said bulk powder and binding particles of said bulk powder.
71 ) The method of claim 70 , wherein the step of binding comprises depositing printing fluid on one or more of said incremental layers according to one or more predetermined patterns.
72 ) The method of claim 71 further comprising the step of removing or reducing the amount of printing fluid in the matrix.
73 ) The method of any one of claims 68 - 72 , wherein the average native particle size is such that not more than 20% wt of the drug is <32 microns, 40-70% wt of the drug is <63 microns, 70-95% wt of the drug is <125 microns, and 100% wt of the drug is <250 microns, and the ratio of average effective particle size to average native particle size is in the range of greater than 1:1 to about 10:1.
74 ) The method of any one of claims 68 - 72 , wherein the native particles of drug have an average, mean or median native particle size in the range of about 1 to about 90 microns, about 1 to about 75 microns, about 1 to about 50 microns, about 1 to about 30 microns, about 1 to about 15 microns, about 1 to about 10 microns, about 2 to about 14 microns, about 10 to about 80 microns, about 20 to about 70 microns, about 20 to about 60 microns or about 30 to about 50 microns.
75 ) The method of any one of claims 68 - 72 , wherein the drug-containing particles have an average, mean or median effective particle size in the range of about 50 to about 400 microns, about 50 to about 300 microns, about 50 to about 250 microns, about 60 to about 250 microns, about 60 to about 100 microns, or about 75 to about 250 microns.
76 ) The method of any one of claim 68 - 75 , wherein:
the drug-containing particles further comprise at least one sweetener and at least one glidant; the matrix comprises particles bound by said second binder; the matrix disperses in less than 15 sec in a volume of 15 ml of aqueous fluid; and/or the content of drug in the matrix is 35-60% wt based upon the total weight of the matrix.
77 ) The method of claim 76 , wherein: a) at least one surfactant is present in an amount of 0.5-7.0% wt based upon the final weight of the matrix; b) the at least one sweetener is present in an amount of 0.01-2.0% wt based upon the final weight of the matrix; c) the at least one first binder and the at least one second binder are together present in an amount of 5-15% wt based upon the final weight of the matrix; d) the at least one first disintegrant and the at least one second disintegrant are together present in an amount of 10-30% wt based upon the final weight of the matrix; and/or e) the at least one glidant is present in an amount of 0-2% wt based upon the final weight of the matrix.
78 ) The method of any one of claims 68 - 77 , wherein: a) the native particles of drug possess a bi-modal or multi-modal particle size distribution; b) the drug-containing particles possess a mono-modal, bi-modal or multi-modal particle size distribution; c) the ratio of average, mean or median effective particle size to average, mean, or median, respectively, native particle size ranges from 2:1 to 100:1 or 3:1 to 50:1; or d) a combination of one or more of the above.
79 ) The method of any one of claims 68 - 78 further comprising the step of including at least one second surfactant in the bulk powder.
80 ) The method of claim 68 , wherein the method comprises:
forming drug-containing particles comprising at least one first disintegrant, at least one first binder, at least one surfactant, a first grade of native particles of drug and a second grade of native particles of drug, wherein the drug-containing particles have an average, mean or median effective particle size and the first grade of native particles of drug have an average, mean or median first native particle size and the second grade of native particles of drug have an average, mean or median second native particle size, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, first native particle size ranges from greater than 1:1 to about 5:1, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, second native particle size ranges from about 20:1 to about 50:1; combining at least one second disintegrant and at least one second binder with said drug-containing particles to form a bulk powder; and three-dimensionally printing said bulk powder to form one or more of said three-dimensionally printed bound matrix.
81 ) The method of claim 80 , wherein the step of forming drug-containing particles comprises granulating the at least one first disintegrant, at least one first binder, at least one surfactant and native particles of drug.
82 ) The method of claim 80 or 81 , wherein the step of three-dimensionally printing comprises forming plural stacked incremental layers of said bulk powder and binding particles of said bulk powder.
83 ) The method of claim 82 , wherein the step of binding comprises depositing printing fluid on one or more of said incremental layers according to one or more predetermined patterns.
84 ) The method of claim 83 further comprising the step of removing or reducing the amount of printing fluid in the matrix.
85 ) The method of any one of claims 80 - 84 further comprising the step of including at least one second surfactant in the bulk powder.
86 ) A method of preparing a rapidly dispersible porous three-dimensionally printed bound matrix, the method comprising:
forming drug-containing particles comprising at least one first disintegrant, at least one first binder, and native particles of drug, wherein the drug-containing particles have an average, mean or median effective particle size and the native particles of drug have an average, mean or median native particle size, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, native particle size ranges from greater than 1:1 to 200:1; combining at least one surfactant, at least one second disintegrant and at least one second binder with said drug-containing particles to form a bulk powder; and three-dimensionally printing said bulk powder to form one or more of said three-dimensionally printed bound matrix.
87 ) The method of claim 86 , wherein the step of forming drug-containing particles comprises granulating the at least one first disintegrant, at least one first binder, and native particles of drug.
88 ) The method of claim 86 or 87 , wherein the step of three-dimensionally printing comprises forming plural stacked incremental layers of said bulk powder and binding particles of said bulk powder.
89 ) The method of claim 88 , wherein the step of binding comprises depositing printing fluid on one or more of said incremental layers according to one or more predetermined patterns.
90 ) The method of claim 89 further comprising the step of removing or reducing the amount of printing fluid in the matrix.
91 ) The method of any one of claims 86 - 90 , wherein the average native particle size is such that not more than 20% wt of the drug is <32 microns, 40-70% wt of the drug is <63 microns, 70-95% wt of the drug is <125 microns, and 100% wt of the drug is <250 microns, and the ratio of average effective particle size to average native particle size is in the range of greater than 1:1 to about 10:1.
92 ) The method of any one of claims 86 - 90 , wherein the native particles of drug have an average, mean or median native particle size in the range of about 1 to about 90 microns, about 1 to about 75 microns, about 1 to about 50 microns, about 1 to about 30 microns, about 1 to about 15 microns, about 1 to about 10 microns, about 2 to about 14 microns, about 10 to about 80 microns, about 20 to about 70 microns, about 20 to about 60 microns or about 30 to about 50 microns.
93 ) The method of any one of claims 86 - 90 , wherein the drug-containing particles have an average, mean or median effective particle size in the range of about 50 to about 400 microns, about 50 to about 300 microns, about 50 to about 250 microns, about 60 to about 250 microns, about 60 to about 100 microns, or about 75 to about 250 microns.
94 ) The method of any one of claim 86 - 93 , wherein:
the drug-containing particles further comprise at least one sweetener and at least one glidant; the matrix comprises particles bound by said second binder; the matrix disperses in less than 15 sec in a volume of 15 ml of aqueous fluid; and/or the content of drug in the matrix is 35-60% wt based upon the total weight of the matrix.
95 ) The method of claim 94 , wherein: a) the at least one surfactant is present in an amount of 0.5-7.0% wt based upon the final weight of the matrix; b) the at least one sweetener is present in an amount of 0.01-2.0% wt based upon the final weight of the matrix; c) the at least one first binder and the at least one second binder are together present in an amount of 5-15% wt based upon the final weight of the matrix; d) the at least one first disintegrant and the at least one second disintegrant are together present in an amount of 10-30% wt based upon the final weight of the matrix; and/or e) the at least one glidant is present in an amount of 0-2% wt based upon the final weight of the matrix.
96 ) The method of any one of claims 86 - 95 , wherein: a) the native particles of drug possess a bi-modal or multi-modal particle size distribution; b) the drug-containing particles possess a mono-modal, bi-modal or multi-modal particle size distribution; c) the ratio of average, mean or median effective particle size to average, mean, or median, respectively, native particle size ranges from 2:1 to 100:1 or 3:1 to 50:1; or d) a combination of one or more of the above.
97 ) The method of claim 86 , wherein the method comprises:
forming drug-containing particles comprising at least one first disintegrant, at least one first binder, a first grade of native particles of drug and a second grade of native particles of drug, wherein the drug-containing particles have an average, mean or median effective particle size and the first grade of native particles of drug have an average, mean or median first native particle size and the second grade of native particles of drug have an average, mean or median second native particle size, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, first native particle size ranges from greater than 1:1 to about 5:1, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, second native particle size ranges from about 20:1 to about 50:1; combining at least one surfactant, at least one second disintegrant and at least one second binder with said drug-containing particles to form a bulk powder; and three-dimensionally printing said bulk powder to form one or more of said three-dimensionally printed bound matrix.
98 ) The method of claim 97 , wherein the step of forming drug-containing particles comprises granulating the at least one first disintegrant, at least one first binder, and native particles of drug.
99 ) The method of claim 97 or 98 , wherein the step of three-dimensionally printing comprises forming plural stacked incremental layers of said bulk powder and binding particles of said bulk powder.
100 ) The method of claim 99 , wherein the step of binding comprises depositing printing fluid on one or more of said incremental layers according to one or more predetermined patterns.
101 ) The method of claim 100 further comprising the step of removing or reducing the amount of printing fluid in the moist matrix.
102 ) The method of any one of claims 68 - 101 , wherein the matrix has been prepared by a three-dimensional printing process employing printing fluid comprising alcohol, glycerin, water, at least one surfactant or a combination thereof.
103 ) A method of preparing a rapidly dispersible porous three-dimensionally printed bound matrix, the method comprising:
forming drug-containing particles comprising at least one first disintegrant, at least one first binder, and native particles of drug, wherein the drug-containing particles have an average, mean or median effective particle size and the native particles of drug have an average, mean or median native particle size, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, native particle size ranges from greater than 1:1 to 200:1; combining at least one second disintegrant and at least one second binder with said drug-containing particles to form a bulk powder; and depositing a printing fluid to said bulk powder to form one or more of said three-dimensionally printed bound matrix, wherein the printing fluid comprises at least one surfactant.
104 ) The method of claim 103 , wherein the step of forming drug-containing particles comprises granulating the at least one first disintegrant, at least one first binder, and native particles of drug.
105 ) The method of claim 103 or 104 , wherein the step of depositing comprises depositing a printing fluid to said bulk powder to bind particles of said bulk powder thereby forming plural stacked incremental layers of said bulk powder which together form one or more of said three-dimensionally printed bound matrix, wherein the printing fluid comprises at least one surfactant.
106 ) The method of any one of claims 103 - 105 , wherein the depositing of printing fluid to said bulk powder is done according to one or more predetermined patterns.
107 ) The method of any one of claims 103 - 106 further comprising the step of removing or reducing the amount of printing fluid in the matrix.
108 ) The method of any one of claims 103 - 107 , wherein the average native particle size is such that not more than 20% wt of the drug is <32 microns, 40-70% wt of the drug is <63 microns, 70-95% wt of the drug is <125 microns, and 100% wt of the drug is <250 microns, and the ratio of average effective particle size to average native particle size is in the range of greater than 1:1 to about 10:1.
109 ) The method of any one of claims 103 - 107 , wherein the native particles of drug have an average, mean or median native particle size in the range of about 1 to about 90 microns, about 1 to about 75 microns, about 1 to about 50 microns, about 1 to about 30 microns, about 1 to about 15 microns, about 1 to about 10 microns, about 2 to about 14 microns, about 10 to about 80 microns, about 20 to about 70 microns, about 20 to about 60 microns or about 30 to about 50 microns.
110 ) The method of any one of claims 103 - 107 , wherein the drug-containing particles have an average, mean or median effective particle size in the range of about 50 to about 400 microns, about 50 to about 300 microns, about 50 to about 250 microns, about 60 to about 250 microns, about 60 to about 100 microns, or about 75 to about 250 microns.
111 ) The method of any one of claims 103 - 110 , wherein:
the drug-containing particles further comprise at least one sweetener and at least one glidant; the matrix comprises particles bound by said second binder; the matrix disperses in less than 15 sec in a volume of 15 ml of aqueous fluid; and/or the content of drug in the matrix is 35-60% wt based upon the total weight of the matrix.
112 ) The method of claim 111 , wherein: a) the at least one surfactant is present in an amount of 0.5-7.0% wt based upon the final weight of the matrix; b) the at least one sweetener is present in an amount of 0.01-2.0% wt based upon the final weight of the matrix; c) the at least one first binder and the at least one second binder are together present in an amount of 5-15% wt based upon the final weight of the matrix; d) the at least one first disintegrant and the at least one second disintegrant are together present in an amount of 10-30% wt based upon the final weight of the matrix; and/or e) the at least one glidant is present in an amount of 0-2% wt based upon the final weight of the matrix.
113 ) The method of any one of claims 103 - 112 , wherein: a) the native particles of drug possess a bi-modal or multi-modal particle size distribution; b) the drug-containing particles possess a mono-modal, bi-modal or multi-modal particle size distribution; c) the ratio of average, mean or median effective particle size to average, mean, or median, respectively, native particle size ranges from 2:1 to 100:1 or 3:1 to 50:1; or d) a combination of one or more of the above.
114 ) The method of any one of claims 103 - 113 further comprising the step of including at least one second surfactant in the bulk powder.
115 ) The method of claim 103 , wherein the method comprises:
forming drug-containing particles comprising at least one first disintegrant, at least one first binder, a first grade of native particles of drug and a second grade of native particles of drug, wherein the drug-containing particles have an average, mean or median effective particle size and the first grade of native particles of drug have an average, mean or median first native particle size and the second grade of native particles of drug have an average, mean or median second native particle size, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, first native particle size ranges from greater than 1:1 to about 5:1, and the ratio of average, mean or median effective particle size to average, mean or median, respectively, second native particle size ranges from about 20:1 to about 50:1; combining at least one second disintegrant and at least one second binder with said drug-containing particles to form a bulk powder; and depositing a printing fluid to said bulk powder to form one or more of said three-dimensionally printed bound matrix, wherein the printing fluid comprises at least one surfactant.
116 ) The method of claim 115 , wherein the step of forming drug-containing particles comprises granulating the at least one first disintegrant, at least one first binder, and native particles of drug.
117 ) The method of claim 115 or 116 , wherein the step of depositing comprises depositing a printing fluid to said bulk powder to bind particles of said bulk powder thereby forming plural stacked incremental layers of said bulk powder which together form one or more of said three-dimensionally printed bound matrix, wherein the printing fluid comprises at least one surfactant.
118 ) The method of any one of claims 115 - 117 , wherein the depositing of printing fluid to said bulk powder is done according to one or more predetermined patterns.
119 ) The method of any one of claims 115 - 118 further comprising the step of removing or reducing the amount of printing fluid in the matrix.
120 ) The method of any one of claims 115 - 119 further comprising the step of including at least one second surfactant in the bulk powder.
121 ) The method of any one of claims 103 - 120 , wherein the printing fluid further comprises alcohol, glycerin, water, or a combination thereof.
122 ) The method of any one of claims 68 - 121 , wherein: a) the hardness of the matrix ranges from about 1 to about 3 kp or about 1 to about 7 kp; b) the matrix disperses in 15 sec or less or 10 sec or less when placed in 15 ml of water or in saliva; c) the matrix comprises about 150 mg to about 600 mg of drug; and/or d) the matrix comprises 10 to 40 three-dimensionally printed incremental layers.
123 ) The method of any one of claims 68 - 122 , wherein: a) the content of drug-containing particles in the matrix is 55-85% wt, 60-80% wt or 65-70% wt based upon the total weight of matrix in the final dosage form; b) the content of native particles of drug in the drug-containing particles is 55-85% wt, 60-80% wt or 65-70% wt, based upon the final weight of the drug-containing particles; c) the content of first disintegrant in the drug-containing particles ranges up to 30%, 1-15%, or 2-5% wt, based upon the final weight of the drug-containing particles; d) the content of first binder in the drug-containing particles ranges up to 10%, 1-7%, or 2-5% wt, based upon the final weight of the drug-containing particles; e) the content of surfactant in the bulk powder ranges up to 10%, 1-5%, or 1.4-4.2% wt, based upon the final weight of the bulk powder; and/or f) the drug-containing particles are manufactured by wet granulation.
124 ) The method of any one of claims 68 - 123 , wherein the matrix comprises about 150 to about 1200 mg, about 150 mg, about 300 mg, about 450 mg, about 600 mg, about 750 mg, about 900 mg, about 1050 mg or about 1200 of drug.
125 ) The method of any one of claims 68 - 124 , wherein: a) the first binder and second binder are independently selected at each occurrence from the group consisting of polyvinylpyrrolidone, mannitol, hydroxypropylcellulose, and a combination thereof; b) the first disintegrant and the second disintegrant are independently selected at each occurrence from the group consisting of microcrystalline cellulose, a combination of two grades of microcrystalline cellulose, croscarmellose, and a combination thereof; or c) a combination of the above.
126 ) The method of any one of claims 68 - 125 , wherein: a) the drug-containing particles comprise at least two first disintegrants and at least one binder; b) the matrix comprises at least two second binders and at least one second disintegrant; or c) a combination of any of the above.
127 ) The method of any one of claims 68 - 126 , wherein: a) at least one first binder is different than the at least one second binder; b) at least one first disintegrant is different than the at least one second disintegrant; c) at least one first binder is the same as the at least one second binder; d) at least one first disintegrant is the same as the at least one second disintegrant; or e) a combination of any of the above.
128 ) A rapidly dispersible porous non-compressed three-dimensionally printed bound matrix comprising:
55-85 wt % of drug-containing particles comprising at least one first disintegrant, at least one first binder, and native particles of drug; up to 10 wt % of surfactant based upon the final weight of the matrix, wherein the surfactant is included in the drug-containing particles, included in material excluding the drug-containing particles, or include in both; 3-20 wt % of at least one second disintegrant; 10 wt % to 45 wt % at least one second binder; wherein: the hardness of the matrix ranges from about 1 to about 7 kiloponds; the matrix comprises about 150 mg to about 1200 mg of drug; and the weight percentages are based upon the final weight of the matrix, thereby providing the rapidly dispersible porous non-compressed three-dimensionally printed bound matrix.
129 ) The matrix of claim 128 , wherein the surfactant is present in the material excluding the drug-containing the particles.
130 ) The matrix of claim 128 or 129 , wherein the surfactant is present in the drug-containing particles.
131 ) The matrix of any one of claim 128 , 129 , or 130 , wherein the drug-containing particles comprise 55 wt % to 85 wt % of drug based upon the final weight of the drug-containing particles.
132 ) The matrix of any one of claim 128 - 130 or 131 , wherein the drug-containing particles comprise 15-35 wt % of disintegrant based upon the final weight of the drug-containing particles.
133 ) The matrix of any one of claim 128 - 130 or 131 , wherein the drug-containing particles comprise up to 30 wt % of disintegrant based upon the final weight of the drug-containing particles.
134 ) The matrix of any one of claim 128 - 132 , or 133 , wherein the drug-containing particles comprise up to about 10 wt % of binder based upon the final weight of the drug-containing particles.
135 ) The matrix of any one of claim 128 - 133 , or 134 , wherein the drug-containing particles comprise up to about 10 wt % of surfactant based upon the final weight of the drug-containing particles.
136 ) The matrix of any one of claim 128 - 134 , or 135 , wherein the content of drug in the matrix ranges from 35-60 wt % based upon the final weight of the matrix.
137 ) The matrix of any one of claim 128 - 135 , or 136 , wherein the content of binder in the matrix ranges from 5-15 wt % based upon the final weight of the matrix.
138 ) The matrix of any one of claim 128 - 136 , or 137 , wherein the content of disintegrant in the matrix ranges from 10-30 wt % based upon the final weight of the matrix.
139 ) The matrix of any one of claim 128 - 137 , or 138 , wherein the matrix comprises 0.5-7.0 wt % of surfactant based upon the final weight of the matrix.
140 ) The matrix of any one of claim 128 - 138 , or 139 , wherein the matrix comprises not more than 10 wt % of moisture based upon the final weight of the matrix.
141 ) The matrix of claim 140 , wherein the matrix comprises at least 0.1 wt % moisture based upon the final weight of the matrix.
142 ) The matrix of any one of claim 128 - 140 , or 141 , wherein the matrix further comprises one or more of the following: a) at least one glidant present in an amount of up to 2 wt % based upon the final weight of the matrix; b) at least one sweetener present in an amount in the of range 0.01-2.0 wt % based upon the final weight of the matrix; c) flavorant present in an amount of up to 10 wt % based upon the final weight of the matrix; d) glycerin present in an amount of up to 2 wt % based upon the final weight of the matrix; or e) a combination of two or more thereof.
143 ) The matrix of any one of claim 128 - 141 , or 142 , wherein: a) the native particles of drug possess a bi-modal or multi-modal particle size distribution; b) the drug-containing particles possess a mono-modal, bi-modal or multi-modal particle size distribution; or c) a combination of one or more of the above
144 ) The matrix of any one of claim 128 - 142 , or 143 , wherein the drug-containing particles have an average, mean or median effective particle size in the range of about 50 to about 400 microns.
145 ) The matrix of claim 144 , wherein the native particles of drug have an average, mean or median native particle size in the range of about 1 to about 90 microns, or have a particle size distribution characterized by a Dv90 of less than about 100 microns, have a Dv50 of less than about 75 microns, and a Dv10 of less than about 30 microns.
146 ) The matrix of claim 145 , wherein the drug-containing particles have a ratio of effective particle size to native particle size of up to about 200:1.
147 ) The matrix of claim 145 , wherein the drug-containing particles comprise a first population of particles having a ratio of effective particle size to native particle size of greater than 1:1 up to about 5:1 and a second population of particles having a ratio of effective particle size to native particle size of about 20:1 to about 50:1.
148 ) The matrix of claim 144 , wherein the native particles of drug have an average native particle size is such that not more than 20 wt % of the drug is <32 microns, 40-70 wt % of the drug is <63 microns, 70-95 wt % of the drug is <125 microns, and 100 wt % of the drug is <250 microns, and the ratio of average effective particle size to average native particle size is in the range of greater than 1:1 to about 10:1.
149 ) The matrix of any one of claim 128 - 147 , or 148 , wherein the porosity of the matrix ranges from about 10% to about 90% of the matrix volume.
150 ) The matrix of any one of claim 128 - 148 , or 149 , wherein the bulk density of the matrix ranges from 150 mg/mL to about 1300 mg/mL.
151 ) The matrix of any one of claim 128 - 149 , or 150 , wherein the matrix comprises the following types of incremental layers grouped into respective sections of the dosage form: a) a first end comprising plural layers of first solid print pattern; a middle portion comprising plural layers of annular print pattern and plural layers of combination annular and grayscale print pattern; and a second end comprising plural layers of indicum print pattern; b) a first end comprising plural layers of first solid print pattern; a middle portion comprising plural layers of combination annular and grayscale print pattern; and a second end comprising plural layers of first solid print pattern and/or plural layers of indicum print pattern; c) a first end comprising plural layers of first solid print pattern; a middle portion comprising plural layers of annular print pattern, plural layers of combination annular and grayscale print pattern; and a second end comprising plural layers of first solid print pattern and/or plural layers of indicum print pattern; or d) a first end comprising plural layers of first solid print pattern; a middle portion comprising alternating groups of layers, wherein one group comprises plural layers of annular print pattern, and another group comprises plural layers of combination annular and grayscale print pattern; and a second end comprising plural layers of first solid print pattern and/or plural layers of indicum print pattern.
152 ) The matrix of claim 151 , wherein the thickness the incremental layers ranges from 0.005-0.015 inches or from 100-400 μm.
153 ) A rapidly dispersible three-dimensionally printed porous non-compressed bound matrix comprising:
55-65 wt % of drug-containing particles; 2-15 wt % of disintegrant; and 20-45 wt % of binder; wherein: the drug-containing particles comprise:
55-75 wt % of drug;
15-45 wt % of disintegrant;
up to 10 wt % of binder; and
up to 10 wt % of surfactant.
154 ) A rapidly dispersible three-dimensionally printed porous non-compressed bound matrix comprising:
55-85 wt % of drug-containing particles; 2-15 wt % of disintegrant; and 20-45 wt % of binder; wherein: the drug-containing particles comprise:
55-85 wt % of drug;
up to 30 wt % of disintegrant;
up to 10 wt % of binder; and
up to 10 wt % of surfactant.
155 ) A rapidly dispersible three-dimensionally printed porous non-compressed bound matrix comprising drug, binder, disintegrant, and surfactant, wherein:
the matrix comprises particles bound by binder; the matrix disperses in less than 15 sec in a volume of 15 ml of aqueous fluid; the drug is included in drug-containing particles comprising up to 30 wt % of disintegrant based upon the weight of the drug-containing particles, up to 10 wt % of binder based upon the weight of the drug-containing particles, and 55-85 wt % of native particles of the drug based upon the weight of the drug-containing particles; the content of drug-containing particles in the matrix ranges from 55-85 wt % based upon the final weight of the matrix; the content of drug in the matrix ranges from 35-60 wt % based upon the final weight of the matrix; the content of binder ranges from 5-15 wt % based upon the final weight of the matrix; the content of disintegrant ranges from 10-30 wt % based upon the final weight of the matrix; and the content of surfactant ranges from 0.5-7.0 wt % based upon the final weight of the matrix, wherein the surfactant is included in the drug-containing particles, in material excluding the drug-containing particles, or in both.
156 ) A method of treating a disease, condition or disorder that is therapeutically responsive to the comprising administering the matrix of any one of claim 128 - 154 , or 155 one to three times daily to a subject in need thereof throughout a treatment period.Cited by (0)
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