Flashmelt oral dosage formulation

Abstract

There is provided granules for the production of flash-melt pharmaceutical oral dosage forms. In addition to one or more medicaments, the granules are composed of an excipient combination consisting of a superdisintegrant, a dispersing agent, a distributing agent, and a binder and may also include other conventional ingredients such as sweetening and flavoring agents. The subject granules are advantageous in that they are stable and can be prepared without the aid of solvents and without the need for special environments or handling. Dosage forms, especially tablets, prepared therefrom on conventional equipment disintegrate in the mouth in under about twenty five seconds.

1 . A formed pharmaceutical product comprising:
 (a) a pharmaceutically active ingredient; and   (b) a calcium metasilicate excipient having an aspect ratio of average major axial diameter/average minor axial diameter of from about 1.3:1 to about 2.6:1, and an oil absorption of from about 36 ml/100 g to about 51 ml/100 g.   
   
   
       2 . The formed pharmaceutical product of  claim 1 , wherein the pharmaceutical product is in tablet form. 
   
   
       3 . The formed pharmaceutical product of  claim 1 , wherein the pharmaceutical product is in granular form. 
   
   
       4 . The formed pharmaceutical product according to  claim 1 , further comprising a disintegrant selected from the group consisting of starch, modified starch, pregelatinized starch, cellulose, chemically-modified cellulose, sugars, crospovidone and croscarmellose. 
   
   
       5 . A formed pharmaceutical product comprising:
 (a) a pharmaceutically active ingredient; and   (b) a calcium metasilicate excipient having an aspect ratio (average major axial diameter/average minor axial diameter), and an oil absorption range defined by the aspect ratio and oil absorption range defined by the aspect ratio and oil absorption of:
 (i) crystalline alpha triclinic CaSiO 3  from Aldrich Chemical Company; and 
 (ii) crystalline meta CaSiO 3  from Alfa Aesar. 
   
   
   
       6 . The formed pharmaceutical product according of  claim 5 , wherein the crystalline alpha triclinic CaSiO 3  from Aldrich Chemical Company, and the crystalline meta CaSiO 3  from Alfa Aesar, each has about the specifications for surface area, bulk density, true density and volatiles set forth in Table 1 for those materials. 
   
   
       7 . The formed pharmaceutical product of  claim 5  or  claim 6 , wherein the pharmaceutical product is in tablet form. 
   
   
       8 . The formed pharmaceutical product of  claim 5  or  claim 6 , wherein the pharmaceutical product is in tablet form. 
   
   
       9 . The formed pharmaceutical product of  claim 5  or  claim 6 , further comprising a disintegrant selected from the group consisting of starch, modified starch, pregelatinized starch, cellulose, chemically-modified cellulose, sugars, crospovidone and croscarmellose. 
   
   
       10 . The formed pharmaceutical product comprising:
 (a) a pharmaceutically active ingredient; and   (b) a calcium metasilicate excipient selected from the group consisting of;
 (i) crystalline alpha triclinic CaSiO 3  from Aldrich Chemical Company; and 
 (ii) crystalline meta CaSiO 3  from Alfa Aesar. 
   
   
   
       11 . The formed pharmaceutical product according of  claim 10 , wherein the crystalline alpha triclinic CaSiO 3  from Aldrich Chemical Company, and the crystalline meta CaSiO 3  from Alfa Aesar, each has about the specifications for surface area, bulk density, true density and volatiles set forth in Table 1 for those materials. 
   
   
       12 . The formed pharmaceutical product of  claim 10  or  11 , wherein the pharmaceutical product is in tablet form. 
   
   
       13 . The formed pharmaceutical product of  claim 10  or  11 , wherein the pharmaceutical product is in granular form. 
   
   
       14 . The formed pharmaceutical product of  claim 10  or  claim 11 , further comprising a disintegrant selected from the group consisting of starch, modified starch, pregelatinized starch, cellulose, chemically-modified cellulose, sugars, crospovidone and croscarmellose. 
   
   
       15 . A formed product comprising:
 (a) a disintegrant; and   (b) a dehydrated calcium metasilicate excipient having an aspect ratio (average major axial diameter/average minor axial diameter) of from about 1.3:1 to about 2.6:1, and an oil absorption of 36 ml/100 g to about 51 ml/100 g.   
     wherein the formed product disintegrates in about 10 seconds or less when immersed in water. 
   
   
       16 . A formed product comprising:
 (a) a disintegrant; and   (b) a dehydrated calcium metasilicate excipient having an aspect ratio (average major axial diameter/average minor axial diameter), and an oil absorption range about within the aspect ratio range and oil absorption range defined by the aspect ratio and oil absorption of:
 (i) crystalline alpha triclinic CaSiO 3  from Aldrich Chemical Company; and 
 (ii) crystalline meta CaSiO 3  from Alfa Aesar. 
   
     wherein the formed product disintegrates in about 10 seconds or less when immersed in water. 
   
   
       17 . The formed product of  claim 16 , wherein the crystalline alpha triclinic CaSiO 3  from Aldrich Chemical Company, and the crystalline meta CaSiO 3  from Alfa Aesar, each has about the specifications for surface area, bulk density, true density and volatiles set forth in Table 1 for those materials. 
   
   
       18 . A formed product comprising:
 (a) a disintegrant; and   (b) a calcium silicate excipient selected from the group consisting of:
 (i) crystalline alpha triclinic CaSiO 3  from Aldrich Chemical Company; 
 (ii) crystalline meta CaSiO 3  from Alfa Aesar; 
   
     wherein the formed product disintegrates in about 10 seconds or less when immersed in water. 
   
   
       19 . The formed product of  claim 18 , wherein the crystalline alpha triclinic CaSiO 3  from Aldrich Chemical Company, and the crystalline meta CaSiO 3  from Alfa Aesar, each has about the specifications for surface area, bulk density, true density and volatiles set forth in Table 1 for those materials. 
   
   
       20 . A formed pharmaceutical product comprising:
 (a) a pharmaceutically active ingredient; and   (b) a calcium silicate excipient selected from the group consisting of:
 (i) crystalline alpha triclinic CaSiO 3  from Aldrich Chemical Company; 
 (ii) crystalline meta CaSiO 3  from Alfa Aesar; and 
 (iii) crystalline alpha triclinic calcium silicate from Tomita Pharmaceutical Co. 
   
   
   
       21 . The formed product of  claim 20 , wherein the crystalline alpha triclinic CaSiO 3  from Aldrich Chemical Company, and the crystalline meta CaSiO 3  from Alfa Aesar, each has about the specifications for surface area, bulk density, true density and volatiles set forth in Table 1 for those materials, and the crystalline alpha triclinic calcium silicate from Tomita Pharmaceutical Co., meets the following specifications: 1 to 15 m 2 /gm surface area; 0.50 to 0.63 g/cc bulk density; 2.4 to 2.9 g/cc true density; and less than 1% w/w volatiles. 
   
   
       22 . An oral dosage composition comprising a calcium metasilicate having an aspect ratio (average major axial diameter/average minor axial diameter) of from about 1.3:1 to about 2.6:1, and an oil absorption of from about 36 ml/100 g to about 51 ml/100 g. 
   
   
       23 . The oral dosage composition according to  claim 22 , wherein the calcium metasilicate is dehydrated. 
   
   
       24 . The oral dosage composition according to  claim 22 , wherein the calcium metasilicate is wollastonite. 
   
   
       25 . The oral dosage composition according to  claim 22 , further comprising one or more ingredients selected from the group consisting of organoleptic enhancing agents, abrasives, disintegration aids, therapeutic agents and thickening agents. 
   
   
       26 . The oral dosage composition according to  claim 25 , wherein the organoleptic enhancing agent comprises one or more ingredients selected from the group consisting of humectants, sweeteners, flavorants and colorants. 
   
   
       27 . An oral dosage composition comprising:
 a calcium metasilicate having an aspect ratio (average major axial diameter/average minor axial diameter) of from about 1.3:1 to about 2.6:1, and an oil absorption of from about 36 ml/100 g to about 51 ml/100 g;   a disintegration aid; and   an organoleptic agent.   
   
   
       28 . The oral dosage composition of  claim 27 , further comprising one or more ingredients selected from the group consisting of thickening agents, therapeutic agents, sweeteners, and abrasives. 
   
   
       29 . The oral dosage composition of  claim 27 , wherein the organoleptic enhancing agent comprises one or more ingredients selected from the group consisting of humectants, sweeteners, flavorants and colorants. 
   
   
       30 . An oral dosage composition comprising a calcium metasilicate having an aspect ratio (average major axial diameter/average minor axial diameter) of from about 1.3:1 to about 2.6:1, and an oil absorption of from about 36 ml/100 g to about 51 ml/100 g. 
   
   
       31 . The oral tablet composition according to  claim 30 , wherein the calcium metasilicate is dehydrated. 
   
   
       32 . The oral tablet composition according to  claim 30 , wherein the calcium metasilicate is wollastonite. 
   
   
       33 . The oral dosage composition of  claim 30 , further comprising one or more ingredients selected from the group consisting of organoleptic enhancing agents, abrasives, disintegration aids, therapeutic agents and thickening agents. 
   
   
       34 . The oral tablet composition according to  claim 33 , wherein the organoleptic enhancing agent comprises one or more ingredients selected from the group consisting of humectants, sweeteners, flavorants, and colorants.