Carrier pellets, method for production thereof and use thereof

Abstract

The invention relates to a method for the production of carrier pellets for pharmaceutical active substances. Likewise, the invention relates to such carrier pellets and also to pharmaceutical formulations containing these. The carrier pellets according to the invention are used for transporting and releasing pharmaceutical active substances, in particular in the human body.

1 . A method for the production of carrier pellets for a pharmaceutically active substance, the method comprising:
 a) producing a liquid formulation by dissolving, dispersing, or a combination of dissolving and dispersing at least one physiologically well-tolerated pH regulator in at least one solvent or emulsifier,   b) introducing the liquid formulation into a fluidised bed- or spouted bed unit using at least one nozzle,   c) forming essentially spherical carrier pellets by spray granulation in the unit wherein the solvent is evaporated by a drying gas flow and   d) discharging the carrier pellets from the unit.   
     
     
         2 . The method according to  claim 1 ,
 wherein the at least one pH regulator has a regulating effect in physiological surroundings such that the pH value is lowered or increased and the bioavailability of the pharmaceutically active substance is made possible or increased.   
     
     
         3 . The method according to  claim 1 ,
 wherein the at least one pH regulator comprises at least one organic acid selected from the group consisting of ascorbic acid, a C 1 -C 18  mono-carboxylic acid, a C 1 -C 18  di-carboxylic acid, a C 1 -C 18  tricarboxylic acid and mixtures thereof.   
     
     
         4 . The method according to  claim 3 ,
 wherein the at least one organic acid is selected from the group consisting of citric acid, succinic acid, malic acid, fumaric acid, tartaric acid, sorbic acid, adipinic acid, salts thereof, and mixtures thereof.   
     
     
         5 . The method according to  claim 1 ,
 wherein the at least one pH regulator comprises an acidic or basic salt.   
     
     
         6 . The method according to  claim 1 ,
 wherein the pH regulator comprises a buffer system comprising an organic acid and salt of the organic acid or an organic base and salt of the organic base, wherein the buffer system stabilizes the pH.   
     
     
         7 . The method according to  claim 6 ,
 wherein the buffer system comprises citric acid and a citrate or tartaric acid and a tartrate.   
     
     
         8 . The method according to  claim 1 ,
 wherein the pH regulator acts in physiological surroundings as pH-increasing, pH-lowering or pH-stabilising.   
     
     
         9 . The method according to  claim 1 ,
 wherein the pH regulator comprises at least one organic base selected from the group consisting of a purine base, a pyrimidine base, and a mixture thereof.   
     
     
         10 . The method according to  claim 9 ,
 wherein the purine base is selected from the group consisting of adenine, guanine, hypoxanthine, xanthine and mixtures thereof.   
     
     
         11 . The method according to  claim 9 ,
 wherein the pyrimidine base is selected from the group consisting of cytosine, uracil, thymine and mixtures thereof.   
     
     
         12 . The method according to  claim 1 ,
 wherein the pH regulator comprises at least one basic inorganic salt selected from the group consisting of NaHCO 3 , K 2 CO 3 , Na 2 CO 3 , KHCO 3 , Ca(OH) 2 , CaO, phosphates and mixtures thereof.   
     
     
         13 . The method according to  claim 1 ,
 wherein the liquid formulation further comprises at least one physiologically well-tolerated binder.   
     
     
         14 . The method according to  claim 13 ,
 wherein the at least one binder is selected from the group consisting of methyl celluloses, hydroxymethyl celluloses, hydroxypropylmethyl celluloses, alginates, pectins, polyvinylpyrrolidones, xanthanes, hydrocolloids and mixtures thereof.   
     
     
         15 . The method according to  claim 1 ,
 wherein the at least one solvent or emulsifier is water or an organic solvent selected from the group consisting of ethyl alcohol, isopropanol, n-propanol and mixtures thereof.   
     
     
         16 . The method according to  claim 13 ,
 wherein the quantity ratio of pH regulator to binder in the liquid formulation is in the range of 50:50 to 99:1.   
     
     
         17 . The method according to  claim 13 ,
 wherein the liquid formulation contains 30 to 80% by weight of the at least one pH regulator, 0.5 to 5% by weight of the at least one binder and 15 to 69.5% by weight of the at least one solvent.   
     
     
         18 . The method according to  claim 1 ,
 wherein the temperature in the unit is in the range of 5 to 100° C.   
     
     
         19 . The method according to  claim 1 ,
 wherein the drying gas flow has, at the entrance into the unit, a temperature in the range of 5 to 120°.   
     
     
         20 . The method according to  claim 1 ,
 wherein the drying gas is air, nitrogen or inert gas.   
     
     
         21 . The method according to  claim 1 ,
 wherein the spray granulation is effected in a fluidised bed unit into which the drying gas is supplied via a sieve plate and the liquid formulation is introduced by the at least one nozzle disposed above the sieve plate.   
     
     
         22 . The method according to  claim 1 ,
 wherein the spray granulation is effected in a spouted bed unit into which the drying gas is supplied via longitudinal gaps disposed in the lower half of the unit and the liquid formulation is introduced by the at least one nozzle disposed between the longitudinal gaps.   
     
     
         23 . The method according to  claim 22 ,
 wherein the introduction of the liquid formulation is effected through the nozzle from below to above.   
     
     
         24 . A carrier pellet for carrying a pharmaceutically active substance, the carrier pellet comprising at least one physiologically well-tolerated pH regulator, wherein the carrier pellets are produced by the method comprising:
 a) producing a liquid formulation by dissolving, dispersing, or a combination of dissolving and dispersing at least one physiologically well-tolerated pH regulator in at least one solvent or emulsifier,   b) introducing the liquid formulation into a fluidised bed- or spouted bed unit using at least one nozzle,   c) forming essentially spherical carrier pellets by spray granulation in the unit wherein the solvent is evaporated by a drying gas flow and   d) discharging the carrier pellets from the unit.   
     
     
         25 . The carrier pellet according to  claim 24 ,
 wherein the carrier pellet has a diameter in the range of 50 μm to 1.5 mm.   
     
     
         26 . The carrier pellet according to  claim 24 ,
 wherein the carrier pellet is essentially spherical.   
     
     
         27 . The carrier pellet according to  claim 26 ,
 wherein the carrier pellet has a sphericity of 0.8 to 1.0.   
     
     
         28 . The carrier pellet according to  claim 24 ,
 wherein the carrier pellet has a width-length ratio of 0.8 to 1.0.    
     
     
         29 . The carrier pellet according to  claim 24 ,
 wherein the carrier pellet is a dense carrier pellet.   
     
     
         30 . A combination of carrier pellets comprising at least two of the carrier pellets according  claim 24 ,
 wherein at least two of the carrier pellets in the combination have essentially the same size.   
     
     
         31 . A pharmaceutical formulation comprising one or more carrier pellets according to  claim 24  and at least one pharmaceutically active substance. 
     
     
         32 . A method of releasing a pharmaceutically active substance, the method comprising: introducing one or more pharmaceutical formulations according to  claim 31  into physiological surroundings, wherein the one or more carrier pellets releases the pharmaceutically active substance into the physiological surroundings.