Additive for a powder material intended for compaction into shaped bodies

Abstract

The invention relates to an additive for a powder material intended for compaction into shaped bodies. The additive is used to influence the powder material with regard to its cohesion and slidability on foreign surfaces and comprises as the main constituent one or more polyglycerol fatty acids, each obtained by way of a complete or partial esterification of a linear or branched polyglycerol containing two to eight glyceryl units with one or more fatty acids, each containing 6 to 22 carbon atoms.

1 . An additive for influencing the cohesion and lubrication on extrinsic surfaces of a powder provided for mechanical compression into shaped articles and consisting of particles,
 characterized by   one or more polyglycerol fatty acid esters as the main component, respectively obtainable from a complete or partial esterification of a linear or branched polyglycerol containing two to eight glyceryl units with one or more fatty acids each containing 6 to 22 carbon atoms.   
     
     
         2 . The additive as claimed in  claim 1 ,
 characterized in that   the fatty acids on which the polyglycerol fatty acid ester or polyglycerol fatty acid esters are based are saturated or unbranched or both saturated as well as unbranched.   
     
     
         3 . The additive as claimed in  claim 1 ,
 characterized in that   the fatty acids on which the polyglycerol fatty acid ester or polyglycerol fatty acid esters are based contain 16, 18, 20 or 22 carbon atoms.   
     
     
         4 . The additive as claimed in  claim 1 ,
 characterized in that   an investigation of the individual polyglycerol fatty acid ester or polyglycerol fatty acid esters using heat flux differential scanning calorimetry produces, upon heating up, respectively only one endothermic minimum and upon cooling down, respectively only one exothermic maximum.   
     
     
         5 . The additive as claimed in  claim 1 ,
 characterized in that   the polyglycerol fatty acid ester or polyglycerol fatty acid esters have a stable subcellular form below the solidification temperature with a lamellar separation over at least 6 months at 40° C. which is substantially constant according to an evaluation of the Bragg angle determined by WAXS analysis.   
     
     
         6 . The additive as claimed in  claim 1 ,
 characterized in that   the polyglycerol fatty acid ester or polyglycerol fatty acid esters have a stable subcellular form below the solidification temperature with a substantially constant thickness of the lamellar-structured crystallites over at least 6 months at 40° C. according to SAXS analysis evaluated using the Scherrer equation.   
     
     
         7 . The additive as claimed in  claim 1 ,
 characterized by   at least one polyglycerol fatty acid ester from the following group: PG(2)-C18 full esters, PG(2)-C22 partial esters with a hydroxyl value of 15 to 100, PG(2)-C22 full esters, PG(3)-C16/C18 partial esters with a hydroxyl value of 100 to 200, PG(3)-C22 partial esters with a hydroxyl value of 100 to 200, PG(3)-C22 full esters, PG(4)-C16 partial esters with a hydroxyl value of 150 to 250, PG(4)-C16 full esters, PG(4)-C16/C18 partial esters with a hydroxyl value of 150 to 250, PG(4)-C16/C18 full esters, PG(4)-C18 partial esters with a hydroxyl value of 100 to 200, PG(4)-C22 partial esters with a hydroxyl value of 100 to 200, PG(6)-C16/C18 partial esters with a hydroxyl value of 200 to 300, PG(6)-C16/C18 full esters, PG(6)-C18 partial esters with a hydroxyl value of 100 to 200, wherein in the polyglycerol fatty acid esters containing two fatty acid residues which are different because of the number of their carbon atoms, those with a lower number are present in an amount of 35% to 45%, those with a corresponding, complementary higher number are present in an amount of 55% to 65% and the specified full esters preferably have a hydroxyl value of less than 5.   
     
     
         8 . The additive as claimed in  claim 1 ,
 characterized in that   the polyglycerol fatty acid ester or individual polyglycerol fatty acid esters have a solidification temperature of below 75° C. and above 40° C.   
     
     
         9 . The additive as claimed in  claim 1 ,
 characterized in that   the contact angle of the polyglycerol fatty acid ester or individual polyglycerol fatty acid esters during the determination of the hydrophobicity differs by less than 10° from the starting value after 16 weeks at 40° C. as well as at 20° C.   
     
     
         10 . The additive as claimed in  claim 1 ,
 characterized by   post-synthesis mixing of polyglycerol fatty acid esters which are respectively obtainable from esterification reactions which are different because different reaction partners are used or because different reaction conditions are employed.   
     
     
         11 . The additive as claimed in  claim 1 ,
 characterized in that   the median of the diameter of the particle is 1 μm to 300 μm, preferably 5 μm to 15 μm.   
     
     
         12 . Compressed material from an additive as claimed in  claim 1 , and a powder as claimed in  claim 1 ,
 characterized in that   the proportion of additives is no more than 5% by weight, preferably 0.05% to 0.5% by weight.   
     
     
         13 . Compressed material as claimed in  claim 12 ,
 characterized in that   the powder contains a pharmaceutical substance.   
     
     
         14 . The compressed material as claimed in  claim 12 ,
 characterized in that   the powder contains microcrystalline cellulose.   
     
     
         15 . The compressed material as claimed in  claim 12 ,
 characterized by   0.05% to 0.5% by weight of additive and 99.5% to 99.95% by weight of powder, wherein the additive consists of a mixture of respectively 50% by weight of PG(3)-C22 full ester and PG(3)-C22 partial ester with a hydroxyl value of 100 to 200 or entirely of PG(3)-C22 partial ester with the same hydroxyl value.   
     
     
         16 . The compressed material as claimed in  claim 12 ,
 characterized by   a proportion of 15% by weight of metformin-HCl and a proportion of 84.5% to 84.95% by weight of microcrystalline cellulose.   
     
     
         17 . The compressed material as claimed in  claim 12 ,
 characterized by   the property, for a compressed material weight of 285 mg in a cylindrical die with a diameter of 8 mm, of transferring 90% to 99% of the maximum pressing force of 10 kN at the upper punch of a rotary press onto the lower punch.   
     
     
         18 . A process for the preparation of a shaped article from a powder by mechanical compression,
 characterized in that   prior to compression, an additive as claimed in  claim 1 , is added to the powder, preferably prior to feeding to the compression site.   
     
     
         19 . Shaped articles, preferably tablets, produced by mechanical compression in a die, characterized by
 a composition identical to that of the compressed material as claimed in  claim 12 .   
     
     
         20 . The shaped articles as claimed in  claim 19 ,
 characterized in that   the force which is necessary to eject the shaped article from the die under otherwise identical conditions is no more than 150% of the ejection force for a test shaped article for which at least 40% by weight of the additive has been replaced by MgSt and the remainder optionally by the filler employed, preferably microcrystalline cellulose.   
     
     
         21 . The shaped articles as claimed in  claim 19 ,
 characterized by   a breaking strength under a linear effective force of up to 150 N, preferably up to 200 N and particularly preferably up to 250 N.   
     
     
         22 . The shaped articles as claimed in  claim 19 ,
 characterized by   an abrasion of 0.02% to 0.25% by weight, determined in accordance with the European Pharmacopoeia, issue 8.0.   
     
     
         23 . The shaped articles as claimed in  claim 19 ,
 characterized by   a disintegration time of 2 to 4 minutes, tested in accordance with the European Pharmacopoeia, issue 8.0.