Dual use oral pharmaceutical composition tablets of sulfate salts and methods of use thereof

Abstract

The present invention is generally directed to an oral pharmaceutical tablet composition comprising a sulfate salt, for example, sodium sulfate, wherein the composition is capable of administration by direct oral ingestion and by disintegration in water prior to oral ingestion. The present invention is further directed to use of such oral pharmaceutical tablet formulations to induce laxation or to treat or prevent constipation.

1 . An oral solid pharmaceutical composition suitable for administration by direct oral ingestion and by disintegration in water prior to oral ingestion, wherein the composition comprises sodium sulfate and wherein less than 5% by weight of the sodium sulfate comprises sodium sulfate particles that are less than about 150 μm. 
     
     
         2 . The oral solid pharmaceutical composition of  claim 1 , wherein the composition comprises at least about 40% by weight of sodium sulfate. 
     
     
         3 . The oral solid pharmaceutical composition of  claim 2 , wherein the composition comprises at least about 45% by weight of sodium sulfate. 
     
     
         4 . The oral solid pharmaceutical composition of  claim 1 , further comprising potassium sulfate. 
     
     
         5 . The oral solid pharmaceutical composition of  claim 4 , wherein the composition comprises at least about 60% by weight of sodium sulfate and potassium sulfate. 
     
     
         6 . The oral solid pharmaceutical composition of  claim 5 , wherein the composition comprises at least about 65% by weight of sodium sulfate and potassium sulfate. 
     
     
         7 . The oral solid pharmaceutical composition of  claim 1 , wherein less than 4% by weight of the sodium sulfate comprises sodium sulfate particles that are less than about 150 μm. 
     
     
         8 . The oral solid pharmaceutical composition of  claim 7 , wherein less than 3% by weight of the sodium sulfate comprises sodium sulfate particles that are less than about 150 μm. 
     
     
         9 . The oral solid pharmaceutical composition of  claim 1 , wherein at least about 90% by weight of the sodium sulfate comprises sodium sulfate particles that are about 150-700 μm. 
     
     
         10 . The oral solid pharmaceutical composition of  claim 9 , wherein at least about 95% by weight of the sodium sulfate comprises sodium sulfate particles that are about 150-700 μm. 
     
     
         11 . The oral solid pharmaceutical composition of  claim 1 , wherein the composition is a tablet. 
     
     
         12 . The oral solid pharmaceutical composition of  claim 11 , wherein the tablet comprises a coating. 
     
     
         13 . The oral solid pharmaceutical composition of  claim 12 , wherein the coating is a polyvinyl alcohol-polyethylene glycol copolymer. 
     
     
         14 . The oral solid pharmaceutical composition of  claim 1 , wherein the composition comprises at least one excipient selected from the group consisting of a disintegrant, a binder, a lubricant, a flavor and combinations thereof. 
     
     
         15 . The oral solid pharmaceutical composition of  claim 14 , wherein the composition comprises a disintegrant selected from the group consisting Kollidon CL, Kollidon CL-SF, Ludiflash, colloidal silicon dioxide, and combinations thereof. 
     
     
         16 . The oral solid pharmaceutical composition of  claim 14 , wherein the tablet comprises a binder selected from the group consisting of PEG3350, PEG8000, and combinations thereof. 
     
     
         17 . The oral solid pharmaceutical composition of  claim 14 , wherein the tablet comprises a lubricant that is sodium stearyl fumarate. 
     
     
         18 . The oral pharmaceutical composition of  claim 1 , wherein:
 the composition disintegrates in water at about 2° C. or greater in less than about 150 seconds;   the composition disintegrates in water at about 8° C. or greater in less than about 90 seconds;   the composition disintegrates in water at about 5° C. or greater in less than about 120 seconds;   the composition disintegrates in water at about 2° C. or greater in less than about 150 seconds;   the composition does not disintegrate in the mouth in less than about 30 seconds upon direct oral ingestion; or   the composition does not disintegrate in the mouth in less than about 60 seconds upon direct oral ingestion.   
     
     
         19 . An oral solid pharmaceutical composition suitable for administration by direct oral ingestion and by disintegration in water prior to oral ingestion, wherein the composition comprises sodium sulfate and potassium sulfate, wherein less than 5% by weight of the sodium sulfate comprises sodium sulfate particles that are less than about 150 μm, wherein the composition comprises at least about 65% by weight of sodium sulfate and potassium sulfate, and wherein the composition comprises at least about 45% by weight of sodium sulfate. 
     
     
         20 . The oral solid pharmaceutical composition of  claim 19 , wherein less than 4% by weight of the sodium sulfate comprises sodium sulfate particles that are less than about 150 μm. 
     
     
         21 . The oral solid pharmaceutical composition of  claim 20 , wherein less than 3% by weight of the sodium sulfate comprises sodium sulfate particles that are less than about 150 μm. 
     
     
         22 . The oral solid pharmaceutical composition of  claim 19 , wherein the composition comprises at least one excipient selected from the group consisting of a disintegrant, a binder, a lubricant, a flavor, and combinations thereof. 
     
     
         23 . The oral solid pharmaceutical composition of  claim 19 , wherein the composition comprises a disintegrant selected from the group consisting Kollidon CL, Kollidon CL-SF, Ludiflash, colloidal silicon dioxide, and combinations thereof. 
     
     
         24 . The oral solid pharmaceutical composition of  claim 19 , wherein the composition comprises a binder selected from the group consisting of PEG3350, PEG8000, and combinations thereof. 
     
     
         25 . The oral solid pharmaceutical composition of  claim 19 , wherein the composition comprises a lubricant that is sodium stearyl fumarate. 
     
     
         26 . The oral solid pharmaceutical composition of  claim 19 , wherein the composition is a tablet. 
     
     
         27 . The oral solid pharmaceutical composition of  claim 26 , wherein the composition comprises a coating. 
     
     
         28 . The oral solid pharmaceutical composition of  claim 27 , wherein the coating is a polyvinyl alcohol-polyethylene glycol copolymer. 
     
     
         29 . The oral pharmaceutical composition of  claim 20 , wherein:
 the composition disintegrates in water at about 2° C. or greater in less than about 150 seconds;   the composition disintegrates in water at about 8° C. or greater in less than about 90 seconds;   the composition disintegrates in water at about 5° C. or greater in less than about 120 seconds;   the composition disintegrates in water at about 2° C. or greater in less than about 150 seconds;   the composition does not disintegrate in the mouth in less than about 30 seconds upon direct oral ingestion; or   the composition does not disintegrate in the mouth in less than about 60 seconds upon direct oral ingestion.   
     
     
         30 . An oral solid pharmaceutical composition suitable for administration by direct oral ingestion and by disintegration in water prior to oral ingestion, wherein the composition comprises sodium sulfate and potassium sulfate, wherein less than 5% by weight of the sodium sulfate comprises sodium sulfate particles that are less than about 150 μm, wherein the composition comprises at least about 65% by weight of sodium sulfate and potassium sulfate, wherein the composition comprises at least about 45% by weight of sodium sulfate, and wherein the composition comprises Kollidon CL, Ludiflash, colloidal silicon dioxide, PEG3350 or PEG8000, and sodium stearyl fumarate. 
     
     
         31 . The oral solid pharmaceutical composition of  claim 30 , wherein less than 4% by weight of the sodium sulfate comprises sodium sulfate particles that are less than about 150 μm. 
     
     
         32 . The oral solid pharmaceutical composition of  claim 31 , wherein less than 3% by weight of the sodium sulfate comprises sodium sulfate particles that are less than about 150 μm. 
     
     
         33 . The oral solid pharmaceutical composition of  claim 30 , wherein the composition is a tablet. 
     
     
         34 . The oral solid pharmaceutical composition of  claim 33 , wherein the tablet comprises a coating that is a polyvinyl alcohol-polyethylene glycol copolymer. 
     
     
         35 . The oral solid pharmaceutical composition of  claim 34 , wherein the polyvinyl alcohol-polyethylene glycol copolymer Kollicoat IR White II. 
     
     
         36 . A method of preparing the oral solid pharmaceutical composition of  claim 1 , the method comprising the steps of
 (a) blending a batch of sodium sulfate and at least one excipient, wherein less than 5% by weight of the batch of sodium sulfate comprises sodium sulfate particles that are less than about 150 μm; and   (b) compressing the resulting blend into a oral solid pharmaceutical composition.   
     
     
         37 . The method of  claim 36 , further comprising coating the oral pharmaceutical composition. 
     
     
         38 . The method of  claim 36 , further comprising substantially removing sodium sulfate particles less than about 150 μm prior to blending. 
     
     
         39 . A method for inducing laxation in a subject, the method comprising administering to the subject the oral solid pharmaceutical composition of  claim 1 , thereby inducing laxation in the subject. 
     
     
         40 . The method of  claim 39 , wherein the composition is swallowed directly by the subject. 
     
     
         41 . The method of  claim 39 , wherein the step of administering the composition comprises orally ingesting an aqueous dispersion of the composition. 
     
     
         42 . A method for preventing or treating constipation in a subject, the method comprising administering to the subject the oral solid pharmaceutical composition of  claim 1 , thereby treating or preventing constipation in the subject. 
     
     
         43 . The method of  claim 42 , wherein the composition is swallowed directly by the subject. 
     
     
         44 . The method of  claim 42 , wherein the step of administering the composition comprises orally ingesting an aqueous dispersion of the composition.