Dosage form with a core tablet of active ingredient sheathed in a compressed annular body of powder or granular material, and process and tooling for producing it

Abstract

A solid dosage form for oral administration to a patient comprising a core tablet sheathed in an annular body of compressed powder or granular material is provided. A preferred embodiment of the solid dosage form reduces contact of the active ingredient in solid form with the mucosa lining the gastrointestinal tract, which is particularly advantageous for delivering an ulcerative drug. A tool set comprising a columnar punch and a punch assembly comprising an annular punch and core rod, and a tableting process for making the solid dosage form are also provided.

1 - 19 . (canceled)  
     
     
         20 . A toolset for producing a solid pharmaceutical dosage form comprising a core tablet sheathed in a compressed annular body of powder or granular material, the toolset comprising: 
 a) a columnar punch, and    b) a punch assembly comprising an annular punch and a core rod slidably engageable with the annulus of the annular punch, wherein the core rod is capable of movement between a retracted position and an extended position and wherein the core rod is biased in an extended position.    
     
     
         21 . The toolset for producing a solid pharmaceutical dosage form of  claim 20  further comprising a die with a bore therethrough wherein the extent of movement between the retracted and extended positions is approximately equal to or less than the thickness of the die.  
     
     
         22 . The toolset of  claim 20  wherein the columnar punch has a contact face with a centered protrusion.  
     
     
         23 . The toolset of  claim 20  adapted for use in a press having a die table for mounting a die with a bore therethrough such that the axis of the bore is normal to the die table, a first actuated reciprocating ram movable along the axis of the bore and a second actuated reciprocating ram on the opposite side of the die table from the first actuated reciprocating ram movable along the axis of the die bore independently of the first ram, wherein: 
 a) the columnar punch is adapted for mounting to one of the reciprocating rams of the press, and has an end sized to be received in the die bore,    b) the annular punch is adapted for mounting to the other of the reciprocating rams of the press and has an end sized to be received in the die bore, and    c) the punch assembly further comprises a collar adapted for mounting to a fixed point on the press coaxially with the die bore and wherein the core rod is slidably engaged within the annulus of the collar and biased by biasing means housed in the collar.    
     
     
         24 . The toolset of  claim 20  adapted for use in a press having: 
 a generally planar and circular die table capable of rotation about an axis normal to the plane and having a plurality of bores therethrough around its circumference at regular intervals,    a first punch carrier mounted on one side of the die table and a second punch carrier mounted on the other side of the die table, each punch carrier rotating about the axis synchronously with the die table and provided with a plurality of vertical holes or slots for receiving punches, each hole or slot being in registry with a bore through the die table,    means for controlling the motion of punches in the direction of the axis, wherein: 
 a) the columnar punch is adapted for slidable engagement with the holes or slots in the first punch carrier and has an end sized to be received in a bore,  
 b) the annular punch is adapted for slidable engagement with the holes or slots in the second punch carrier and has an end sized to be received in a bore, and  
 c) the core rod is capable of independent motion relative to the annular punch.  
   
     
     
         25 . A process for producing a solid pharmaceutical dosage form comprising forming an annular body of powder or granular material around a core tablet by compression.  
     
     
         26 . The process for producing a solid pharmaceutical dosage form of  claim 25  wherein forming the annular body comprises: 
 a) filling an annular cavity with the powder or granular material, the annular cavity being defined by: 
 i) the bore of a die,  
 ii) an annular punch partially inserted into the bore from one side,  
 iii) a core rod in an extended position wherein it extends through the bore and the annular punch with its tip substantially flush with the surface of the die on the side opposite the annular punch, wherein the core rod is movable between the extended position and a retracted position wherein the tip is inside the bore, and further wherein the core rod is biased in the extended position,  
   b) placing the core tablet at the tip of the core rod, and    c) advancing a columnar punch toward the bore from the side of the die opposite the annular punch, thereby pushing the core tablet into the bore against the bias force on the core rod and causing the core rod to retract, and compressing the powder or granular material around the core tablet, forming the annular body.    
     
     
         27 . The process of  claim 26  wherein the columnar punch contact face has a centered protrusion.  
     
     
         28 . The process for producing a solid pharmaceutical dosage form of  claim 26  further comprising withdrawing at least one of the punches from the die bore after advancing the columnar punch toward the bore and ejecting the solid pharmaceutical dosage form from the bore.  
     
     
         29 . The process for producing a solid pharmaceutical dosage form of  claim 25 , which uses a tablet press equipped with the following parts and tooling: 
 a die table mounting a die with a bore extending therethrough,    a columnar punch mounted on one side of the die table coaxially with the bore and movable along the axis of the bore with the end proximal to the die table sized to be received into the bore and being terminated with a contact face for pressing against the powder or granular material,    an annular punch mounted on the other side of the die table coaxially with the bore and movable along the axis of the die bore independently of the columnar punch, wherein the end of the annular punch proximal to the die table is sized to be received into the die bore and is terminated with a contact face for pressing against the powder or granular material, and    a core rod slidably engaged within the annulus of the annular punch and aligned coaxially with the die bore, the core rod moveable between a retracted position and an extended position wherein the core rod extends through the die bore with the tip of the rod substantially flush with the surface of the die, the core rod being biased to the extended position by biasing means,    wherein forming the annular body comprises: 
 a) filling an annular cavity with the powder or granular material, the annular cavity being defined by the die bore, the core rod in its extended position and the contact face of the annular punch partially inserted into the bore,  
 b) placing the core tablet at the tip of the extended core rod,  
 c) advancing the columnar punch, whereby the core tablet is pushed into the die bore against the bias force exerted by the core rod biasing means, whereby the core rod at least partially retracts, and whereby the powder or granular material is compressed between the contact faces of the columnar and annular punches, forming the annular body.  
   
     
     
         30 . The process for producing a solid pharmaceutical dosage form of  claim 29  further comprising withdrawing at least one of the punches from the die bore after advancing the columnar punch toward the bore and ejecting the solid pharmaceutical dosage form from the bore.  
     
     
         31 . The process of  claim 29  wherein the columnar punch contact face has a centered protrusion.  
     
     
         32 . The process for producing a solid pharmaceutical dosage form of  claim 29  wherein the die table is horizontal, the columnar punch is above the die table, and the annular punch is below the die table, 
 wherein the tablet press is further equipped with a feed shoe for delivering the powder or granular material to the die bore from above and a collar fixedly mounted below the die table coaxially with the die bore, the core rod being slidably engaged within the annulus of the collar and biased by bias means housed in the collar, and    wherein, the annular cavity is filled from the feed shoe, the columnar punch is withdrawn after the advancing step and the solid pharmaceutical dosage form is ejected from the bore by advancing the annular punch into the bore.    
     
     
         33 . The process of  claim 32  wherein the annular cavity is filled by placing the feed shoe over the die bore while the annular punch is positioned with its contact face approximately flush with the die surface and then lowering the lower punch to form the cavity and drawing the powder or granular material into the cavity by gravity or pressure differential.  
     
     
         34 . The process for producing a solid pharmaceutical dosage form of  claim 25  which uses a tablet press equipped with the following parts and tooling: 
 a generally planar and circular die table capable of rotation about an axis normal to the plane and having a plurality of bores therethrough around its circumference at regular intervals,    a first punch carrier mounted on one side the die table and a second punch carrier mounted on the other side of the die table, each punch carrier rotating about the axis synchronously with the die table and provided with a plurality of vertical holes or slots, each hole or slot being in registry with a bore through the die table,    a plurality of annular first punches, each slidably engaged within one of the vertical holes or slots of the first punch carrier, each of the first punches having an end proximal to the die table sized to be received into a bore and being terminated with an annular contact face for pressing against the powder or granular material, each of the first punches further having a core rod slidably engaged within the annulus and aligned coaxially with a die bore, the core rod moveable between a retracted position and an extended position wherein the core rod extends through the die bore with the tip of the rod substantially flush with the surface of the die table, the core rod being biased to the extended position by biasing means,    a plurality of second punches, each slidably engaged within one of the vertical holes or slots of the second punch carrier, each of the second punches having an end proximal to the die table sized to be received into a bore and terminated with a contact face for pressing against the powder or granular material,    means for controlling the motion of the punches in the direction of the axis,    wherein forming the annular body comprises: 
 a) filling an annular cavity with the powder or granular material, the annular cavity being defined by a die bore, a core rod in its extended position and the contact face of a first punch partially inserted into the bore,  
 b) placing the core tablet at the tip of the extended core rod,  
 c) advancing a second punch into the die bore, whereby the core tablet is pushed into the die bore against the bias force exerted by the core rod biasing means, whereby the core rod at least partially retracts, and whereby the powder or granular material is compressed between the contact faces of the first and second punch, forming the annular body.  
   
     
     
         35 . The process for producing a solid pharmaceutical dosage form of  claim 34  further comprising withdrawing at least one of the punches from the die bore after advancing the second punch toward the bore and ejecting the solid pharmaceutical dosage form from the bore.  
     
     
         36 . The process of  claim 34  wherein the second punch contact face has a centered protrusion.  
     
     
         37 . The process of  claim 34  wherein the annular cavity is filled by rotating the die table under a feed shoe while the first punch is positioned with its contact face substantially flush with the die table surface and then retracting the first punch to form the cavity and drawing the powder or granular material into the cavity by gravity or pressure differential.  
     
     
         38 . A solid pharmaceutical dosage form produced by the process of  claim 25.