US2017258763A1PendingUtilityA1

Rapid disperse dosage form

Assignee: APRECIA PHARMACEUTICALS COPriority: Mar 15, 2013Filed: May 16, 2017Published: Sep 14, 2017

Est. expiryMar 15, 2033(~6.7 yrs left)· nominal 20-yr term from priority

Inventors:Jules Jacob Norman Coyle Thomas G. West Donald C. Monkhouse Henry L. Surprenant Nemichand B. Jain

A61K 31/4015A61K 9/0056A61K 9/7007A61K 9/70

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Claims

Abstract

A high dose rapidly dispersing three-dimensionally printed dosage form comprising a high dose of water soluble drug in a porous matrix that disperses in water within a period of less than about 15 seconds is disclosed. Also disclosed are methods of preparing the dosage form and of treating a condition, disease or disorder that is therapeutically responsive to the drug.

Claims

exact text as granted — not AI-modified

1 . A method of three-dimensionally printing a three-dimensionally printed rapidly dispersible dosage form, method comprising:
a) depositing an incremental layer of drug-containing powder onto a surface; b) depositing a sufficient amount of printing fluid onto the incremental layer to bind particles in the drug-containing powder, wherein the printing fluid comprises glycerin and at least one pharmaceutically acceptable solvent; and c) repeating a) and b) thereby forming the three-dimensionally printed rapidly dispersible dosage form.

2 . The method of claim 1 , wherein the pharmaceutically acceptable solvent comprises water or aqueous buffer.

3 . The method of claim 1 , wherein the pharmaceutically acceptable solvent comprises alcohol and water or aqueous buffer.

4 . The method of claim 1 , wherein the printing fluid comprises 1-10% wt glycerin, 55-95% wt water or aqueous buffer, 1-25% wt alcohol.

5 . The method of claim 1 , wherein the printing fluid further comprises surfactant.

6 . The method of claim 5 , wherein the printing fluid comprises 0.1-4% wt of surfactant.

7 . The method of of claim 1 , wherein the printing fluid further comprises water soluble, aqueous fluid soluble, partially water soluble or partially aqueous fluid soluble binder.

8 . The method of claim 7 , wherein the printing fluid comprises 1-20% wt water soluble, aqueous fluid soluble, partially water soluble or partially aqueous fluid soluble binder.

9 . The method of claim 1 , wherein the printing fluid further comprises flavorant.

10 . The method of claim 9 , wherein the printing fluid comprises 0.01-5% wt of flavorant.

11 . The method of claim 1 , wherein the drug-containing powder comprises drug, disintegrant and water soluble binder.

12 . The method of claim 1 , wherein the dosage form comprises 50-80% wt of drug, 3-35% wt of disintegrant, 0.5-20% wt of water soluble binder, and 0.05-5% wt of glycerin.

13 . The method of claim 1 , wherein the dosage form further comprises one or more surfactants.

14 . The method of claim 13 , wherein the dosage form further comprises 0.05-1% wt of one or more surfactants.

15 . The method of claim 1 , wherein the dosage form further comprises one or more antioxidants.

16 . The method of claim 15 , wherein the dosage form further comprises 0.005-5% wt of one or more antioxidants.

17 . The method of claim 15 , wherein the printing fluid and/or drug-containing powder comprises one or more antioxidants.

18 . The method of claim 1 , wherein the method comprises:
a) depositing an incremental layer of drug-containing powder comprising drug, disintegrant, binder, and antioxidant; b) according to a predetermined saturation level, depositing a sufficient amount of the printing fluid onto the incremental layer to bind particles in the drug-containing powder and to form an incremental printed layer; and c) repeating a) and b) at least two times, thereby forming the three-dimensionally printed rapidly dispersible dosage form comprising at least three stacked incremental printed layers, wherein: the printing fluid comprises water, alcohol, at least one binder, at least one antioxidant, glycerin, and at least one surfactant.

19 . The method of claim 18 , wherein the content of glycerin in the printing fluid ranges from &gt;0% to 20% wt.

20 . The method of claim 19 , wherein the content of water in the printing fluid is 55-95% wt.

21 . The method of claim 20 , wherein the content of alcohol in the printing fluid is 1-25% wt.

22 . The method of claim 21 , wherein the content of surfactant in the printing fluid is 0.1-4% wt.

23 . The method of claim 22 , wherein the content of water or aqueous buffer in the printing fluid is 55-95% wt.

24 . The method of claim 18 , wherein the binder is water soluble, aqueous fluid soluble, partially water soluble or partially aqueous fluid soluble binder and the content of binder is 1-20% wt.

25 . The method of claim 18 , wherein the content of glycerin in the dosage form ranges from about 0.05%-3% wt or from 0.05-5% wt based upon final weight of the dosage form.

26 . The method of claim 18 , wherein the dosage form comprises 0.005% to about 5.0% wt of antioxidant.

27 . The method of claim 18 , wherein the dosage form comprises 50-80% wt of drug, 3-35% wt of disintegrant, 0.5-20% wt of binder, 0.05-5% wt of glycerin, 0.05-1% wt of surfactant, and 0.005-5% wt of antioxidant.

28 . The method of claim 1 , wherein the dosage form comprises the following ingredients:

Ingredient
Amt (% wt)

Drug
60-70

Disintegrant
20-25

Binder
10-15

Antioxidant
0.005-5.0

Sweetener
0.5-2

Glidant
0.1-1.5

Glycerin
0.1-5

Surfactant
0.05-1.5

Flavor
0-0.5.

29 . The method of claim 1 , wherein the printing fluid comprises the following ingredients:

Water (% wt)
65-72
65-70

Glycerin (% wt)
3.5-4
3.4-4.2

Alcohol (% wt)
12-13.5
11-13

Surfactant (% wt)
1-2
1.5-2.5

Water soluble binder (% wt)
8.5-10
8-10

Sweetener (% wt)
&gt;0-5
4-6

Sweetener (% wt)
0-0.6
0.1-0.8

Flavor
0-0.2
&gt;0-0.1

Flavor
0-0.5.

30 . The method of claim 1 , wherein the dosage form disperses in about 15 sec or less in a volume of about 15 ml or less of water or saliva, and the dosage form has a hardness of at least 1 kp.

31 . The method of claim 1 , wherein the drug is water soluble.

32 . The method of claim 1 , wherein: a) the dosage form is not compressed; b) the exterior of the dosage form is harder than the interior of the dosage form; c) the dosage form comprises not more than 10% wt and not less 0.1% moisture as determined by loss on drying at 120° C.; d) the hardness of the dosage form is substantially uniform; e) the dosage form comprises one or more other medicaments; or f) a combination thereof.

33 . The method of claim 1 , wherein the dosage form comprises about 250 mg to about 1000 mg of drug.

34 . The method of claim 1 , wherein: a) the dosage form comprises 15 to 50 printed incremental layers; b) the thickness of an incremental layer ranges from 0.008 to 0.012 inches; c) the dosage form is porous and non-compressed; or d) a combination thereof.

35 . The method of claim 1 , wherein the dosage form is preservative free.

36 . The method of claim 1 , wherein the hardness of the dosage form is about 2 to about 6 kp or about 3 to about 9 kp.

37 . The method of claim 1 , wherein the drug-containing powder or printing fluid further comprises at least one flavorant, at least one sweetener, and/or at least one preservative.

38 . The method of claim 1 , wherein the porosity of the matrix ranges from about 10% to about 90%.

39 . The method of claim 1 , wherein the bulk density of the matrix ranges from 150 mg/mL to about 1300 mg/mL.

40 . The method of claim 1 , wherein the drug-containing powder comprises up to 15% wt of binder, and 1-30% wt of disintegrant.

41 . The method of claim 40 , wherein the drug-containing powder further comprises at least one of the following: a) up to 5% wt of sweetener; b) 0.1-10% wt of flavorant-loaded carrier; c) 0.1-2% wt of glidant.

42 . The method of claim 40 , wherein the drug-containing powder comprises drug in an amount ranging from 65% to 75% wt or 75% to 90% wt.

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