Patent Publication Number: US-2004056375-A1

Title: Method and apparatus for making miniature tablets

Description:
CROSS REFERENCE TO RELATED APPLICATION  
     [0001] This application claims priority to U.S. Provisional Application No. 60/397,128, filed on Jul. 19, 2002, the disclosure of which is hereby incorporated by reference in its entirety. 
    
    
     
       BACKGROUND OF THE INVENTION  
       [0002] 1. Field of the Invention  
       [0003] The present invention relates to a method and apparatus for making miniature tablets in which a tablet press is used having a predetermined compression force to form miniature tablets having a size of less than about three millimeters (mm) and weighing less than about 10 mg each.  
       [0004] 2. Description of the Prior Art  
       [0005] One conventional, commonly used drug delivery system comprises a capsule filled with drug coated or drug layered non-pareil beads or drug loaded beads. Extrusion processes are used for forming the drug loaded beads. This process has the disadvantage that the extrusion process is complicated and time sensitive. The extrusion process also produces beads that are non-uniform in weight and steps must be taken to ensure that the variation in size from bead to bead is less than 10% in order to meet USP guidelines (each bead being less than 120 mg). The variation in size from bead to bead results in variation in the amount of drug applied to or loaded in each bead. Accordingly, there is little consistency in the amount of drug provided by each bead.  
       [0006] Further, when the drug is applied to the outside of the non-pareil bead, as opposed to being part of the matrix itself, there is always a risk that some of the drug may be sheared off the non-pareils, such as during handling of the non-pareils between when the drug has been applied and when the non-pareils are subjected to coating prior to being filled into capsules, thereby resulting in inconsistency from bead to bead in drug content. The wet granulation extrusion process is extremely sensitive to the types of powders that are blended together, granulated and then extruded to form the drug containing beads. The use of hydrophilic polymers is problematic because these polymers produce a pasty extrudate which is impossible to spheronize into small 0.5 mm to 3 mm beads.  
       [0007] Tablet press machines are known for compacting materials into solid form by exerting force on at least one set of two opposing punches entering a plurality of dies containing the material to be compacted. U.S. Pat. No. 4,362,493 describes that a conventional rotary tablet-making machines comprise a rotary turntable which carries near its periphery an annular series of die cavities in which the dies are clamped. Above and below the die turntable are upper and lower punches carried for rotation with the turntable, there being one upper and one lower punch for each die cavity. The heads of the punches may be guided by raising and lowering camming surfaces to control their reciprocating movements into or out of the die cavities as the die turntable rotates through filing, weight adjusting, compression and ejection stations all spaced around the single turntable.  
       [0008] Conventional tablet press machines have been used to form pharmaceutical tablets and caplets. Typical tablet weights are in the range of 350 to 500 mg. Compression force is applied by a set of compression rollers that the upper and lower punches travel under. The rolls are designed to produce compression forces in the range of 50 kilo-Newtons (kN) to 100 kN in order to compress the material to form the size tablet shape.  
       [0009] Multi-tip tooling has been used to provide small forces per tip. The overall force provided is the sum of all the tips which may be 2.4 kN for 12 tips. Multi-tip tooling has the drawback of being very expensive and provides no tablet weight control mechanism.  
       SUMMARY OF THE INVENTION  
       [0010] The present invention relates to a method and system for forming a miniature tablet using a predetermined compression force in a rotary tablet press. The predetermined compression force can be in the range of about 50 to about 2,000 Newtons, preferably less than about 500 Newtons. It has been found that the use of conventional tablet press designed to apply forces in the range of about 50 kilo-Newtons to 100 kilo-Newtons in a tablet press have the drawback of breakage of tooling used for making a miniature tablet. For example, the punch stems used in forming a miniature tablet have a diameter slightly smaller than the diameter of the miniature tablet which is less than about 3 mm. The slender punch stems are prone to breakage if used with conventional compression machines, thereby interrupting production of the miniature tablets while the tooling is replaced. In one embodiment, the predetermined compression force is applied using an adjustable ramp for moving a lower punch upwardly towards a downwardly moving upper punch wherein the miniature tablet is formed in a die receiving the lower punch and the upper punch. The height of the adjustable ramp is accurately controlled to precisely provide the predetermined compression force for forming the miniature tablet. Conventional main compression rolls are impractical to provide forces in the range of about 50 to about 2,000 kilo-Newtons because they are not capable of being controlled for this subtlety or repeatability and are not capable of measuring the small compression forces with any accuracy.  
       [0011] It has also been found that breakage of punch stems formed on the lower punch can be reduced by providing a reinforced portion of the punch stem below the slender portion of the punch stem which enters a bore of the die wherein the miniature tablet is formed. The reinforced portion of the punch stem is received in a counterbore portion of the die. A fill cam is adjusted to raise the position of the lower punch in order to maintain the punch stem in the bore of the die and prevent any material used for forming the miniature tablets from entering the counterbore of the die during filling of the die. A pull down cam is similarly adjusted to maintain the punch stem of the lower punch within the bore of the die. In an embodiment of the present invention, the paddle feeder speed is accurately controlled to reduce the speed by at least a factor of 6 from conventional feeder speeds in order to feed the small amount of tablet mixture used for forming a miniature tablet.  
       [0012] In an alternate embodiment, the diameter of the conventional punches is reduced and the die height is smaller to reduce the column effect of using a very slender punch stem. The reduction in diameter of the punches allows additional stations to be provided on a similar sized rotatable conventional turret.  
       [0013] The present invention also provides a device for measuring mechanical strength of a formed tablet. In addition, the present invention provides a miniature tablet formed by the process of the present invention. The miniature tablet can be used in place of extruded beads or coated non-pareils to provide drug delivery from a capsule. The present invention also provides more consistency in drug content than that provided by non-pareil beads. The present invention provides an economical method of making miniature tablets without using complex extrusion and spheronization processes.  
       [0014] The invention will be more fully described by reference to the following drawings. 
     
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
     [0015]FIG. 1 is a perspective view of a tablet press apparatus in accordance with the teachings of the present invention.  
     [0016]FIG. 2 illustrates the miniature tablet of the present invention in comparison to a conventional tablet.  
     [0017]FIG. 3 is a schematic diagram of areas of the tablet press used in combination with a lower punch during a tablet press cycle.  
     [0018]FIG. 4 illustrates the tablet press apparatus.  
     [0019]FIG. 5 illustrates a paddle control mechanism.  
     [0020]FIG. 6A is a schematic diagram of a fill cam in combination with a lower punch.  
     [0021]FIG. 6B is a schematic diagram of a fill cam in combination with a reinforced portion of the lower punch and a counterbore of a die in which the punch stem is in the counterbore.  
     [0022]FIG. 6C is a schematic diagram of a fill cam in combination with a reinforced portion of the lower punch and a counterbore of a die in which the punch stem is in the bore of the die.  
     [0023]FIG. 6D is a perspective view of a fill cam having an aperture positioned at a bottom edge of the fill cam.  
     [0024]FIG. 6E is a perspective view of a fill cam having an aperture positioned at a distance above the bottom edge.  
     [0025]FIG. 7 illustrates an upper cam in combination with an upper punch.  
     [0026]FIG. 8 illustrates a weight cam.  
     [0027]FIG. 9 illustrates a scraper bar.  
     [0028]FIG. 10 is a perspective view of a pull down cam.  
     [0029]FIG. 11A is a schematic view of a compression ramp and control mechanism.  
     [0030]FIG. 11B is a top plan view of the compression ramp and control mechanism.  
     [0031]FIG. 12A is a schematic diagram of adjustable ramp during compression between an upper die and a lower die.  
     [0032]FIG. 12B is a schematic diagram of adjustable ramp during compression between an upper die and a lower die.  
     [0033]FIG. 12C is a schematic diagram of adjustable ramp during compression between an upper die and a lower die.  
     [0034]FIG. 13 is a schematic diagram of a prior art compression wheel.  
     [0035]FIG. 14 illustrates a headroom plate and transducer.  
     [0036]FIG. 15 is a schematic diagram of a mechanical strength testing apparatus.  
     [0037]FIG. 16 is a perspective view of an alternate embodiment in accordance with the teachings of the present invention.  
     [0038]FIG. 17 is a schematic diagram of areas of the tablet press used in combination with a lower punch during a tablet press cycle.  
     [0039]FIG. 18 is a schematic diagram of a lower punch used in the press of claim 16. 
    
    
     DETAILED DESCRIPTION  
     [0040] Reference will now be made in greater detail to a preferred embodiment of the invention, an example of which is illustrated in the accompanying drawings. Wherever possible, the same reference numerals will be used throughout the drawings and the description to refer to the same or like parts.  
     [0041]FIG. 1 illustrates a perspective view of tablet press apparatus  10  in accordance with the teachings of the present invention. Tablet press apparatus  10  is used to form miniature tablets  12 , as shown in FIG. 2. Miniature tablets  12  have a size and shape that is chosen as desired. Miniature tablets  12  have a substantially spherical shape. Miniature tablets  12  have a size in the range of about 0.5 mm to about 5.0 mm in diameter with preferred sizes of about 1.0 mm, about 1.5 mm and about 2.0 mm in diameter. The weight of miniature tablet  12  depends upon its components and size. A 2 mm diameter miniature tablet  12  typically weighs about 3 to about 10 milligrams (mg). Miniature tablets  12  can be formed having the following shapes ball, round, oval, capsule and square, all with different complexities, such as shallow, standard and deep. Any tablet geometry traditionally used in larger sized tablets can be fabricated in accordance with the teachings of the present invention. Conventional tablets  11  typically have a diameter of about 10 mm or greater.  
     [0042] Referring to FIGS. 1 and 4, tablet press apparatus  10  of the present invention comprises a modified Riva Piccola 10-station tablet press. Tablet press apparatus  10  includes frame  13  for mounting various components. Turret  16  rotatable by an electrically powered drive mechanism  17  is mounted underneath support plate  15 . In this embodiment of the invention turret  16  includes upper turret portion  16   a  having openings extending vertically therethrough which receive upper punches  68 , lower turret portion  16   b  having openings extending vertically therethrough which receive lower punches  28  and central turret portion  16   c  into which dies  40  are mounted. Openings in upper turret portion  16   a  are aligned with corresponding openings in lower turret portion  16   b  and corresponding dies of central turret portion  16   c . Turret  16  is provided with a number of possible stations, for example 10 stations and a predetermined number of stations can be in use.  
     [0043] Referring to FIGS. 3A, 3B and  4 , tablet fill area  14  is used for filling a die with an amount of tablet mixture from which miniature tablets  12  are made. Hopper  18  feeds the tablet mixture to paddle feeder  20  which distributes the tablet mixture uniformly and evenly into die  40 . Control module for paddle feeder  22  is provided in the present invention for controlling paddle speeds used in a conventional Riva Piccola press, as shown in FIG. 5. It has been found that typical paddle speeds of up to 60 RPM used in the conventional Riva Piccola press for producing tablets having a size of about 10 mm and weights in the range of 350 mg to 500 mg do not provide proper fill for producing tablets having weights of less than about 10 mg. Control module for paddle feeder  22  reduces the paddle speeds used in the conventional Riva Piccola press by a factor of 6 in order to optimize feed into dies  40 . Control module for paddle feeder  22  can comprise electronics coupled to paddle feeder  20 .  
     [0044] Referring to FIGS. 1, 3 and  6 , as each station moves into tablet fill area  14 , fill cam  24  is used to fill die  40  by a pre-determined amount of the tablet mixture by placement of fill cam  24  to create sufficient tablet mixture fill depth within bore  44  of die  40 . Bore  44  is sized to have a diameter corresponding to the diameter of miniature tablet  16 . Die  40  is typically filled with an amount greater than the amount needed in the formed miniature tablet  12 . For example, about 7 mg to about 8 mg are filled into die  40  in tablet fill area  14  to form a tablet having a desired weight of about 5 mg.  
     [0045] Fill cam  24  includes aperture  26  for receiving punch head  32  of lower punch  28 . Lower punch has a cylindrical body portion connecting punch stem  38  positioned at upper portion  34  of lower punch  28  to punch head  32  positioned at lower portion  30  for engagement with fill cam  24  and various other cams of tablet press apparatus  10 . Punch stem  38  is sized to have a diameter to fit snugly in bore  44 . Punch stem  38  has a length such that punch stem  38  can be received in bore  44  during tablet making and a portion, punch tip  39 , can extend through the length of bore  44  to outside of die  40  for ejecting a formed tablet from bore  44 . For example, punch stem  38  can have a diameter slightly smaller than a size of bore  44  for each size of miniature tablet  16 , such as about 0.025 mm to about 0.0375 mm less than the diameter of bore  44  which can be in the range of about 1.0875 mm to about 2.0125 mm for a 2.0 mm tablet. In an embodiment of the present invention, end of punch tip  39  is concave to impart a convex shape to a lower side of miniature tablets  12 .  
     [0046] As each station enters tablet fill area  14 , fill cam  24  engages punch head  32  of lower punch  28  associated with the station moving through tablet fill area  14  and directs lower punch  28  downwardly as it passes through tablet fill area  14 , resulting in punch stem  38  being pulled downwardly in bore  44  of die  40  a pre-determined amount as set by placement of fill cam  24  to create sufficient fill depth inside bore  44 . In addition to gravity, the mixture for forming the miniature tablets flows into bore  44  of die  40  due to a suction effect created as punch stem  38 , which fits snugly in bore  44 , moves downwardly within bore  44 .  
     [0047] It has been found that a punch stem  38  having a diameter of less than about 2.0 mm, as shown in FIG. 6A, can be prone to breakage during compression forces used in a conventional tablet press. In an embodiment of the present invention, lower punch  28  includes reinforced body portion  36  at upper end  34  of lower punch  28 , as shown in FIGS. 6B and 6C. Reinforced body portion  36  is received in counterbore portion  42  of die  40  to reduce the length to diameter ratio and reduce a column effect created by the use of a long slender design for punch stem  28 .  
     [0048] Conventional fill cam  24  of the Riva Piccola tablet press, as shown in FIG. 6A, includes aperture  26  positioned at bottom edge  27  to withdraw fill cam all the way down and position punch stem  38  in lower portion  46  of bore  44 , as shown in FIG. 6C. It has been found that if conventional fill cam  24  is used with counterbore portion of die  40 , punch stem  38  does not extend into lower portion  46  of bore  44  of die  40 , as shown in FIG. 6B, thereby allowing the mixture for forming the tablet to escape. In an embodiment of the present invention, fill cam  24  was modified to position aperture  26  at a distance D1 from bottom edge  27  of fill cam  24  in order to position reinforced body portion  36  always within counterbore portion  42  and at least a portion of punch stem  38  is always within lower portion  46  of bore  44 , as shown in FIGS. 6C and 6E. Accordingly, in this embodiment because punch stem  38  is never completely withdrawn from lower portion  46  of bore  44  the mixture for forming the miniature tablets is retained in bore  44  by punch stem  38  and is prevented from flowing into counterbore portion  42  from bore  44 .  
     [0049] Referring to FIG. 7, in tablet fill area  14  the positioning of upper punch  68  is directed by upper cam  89  for positioning upper punch  68  above and out of die  40 .  
     [0050] Referring to FIG. 3, upon exiting tablet fill area  14 , the station enters weight adjustment area  50  where the amount of the mixture for forming the tablet in bore  44  of die  40  is adjusted to correspond to the weight desired for miniature tablet  12 . Weight adjustment area  50  includes weight cam  52 , as shown in FIG. 8. Weight cam  52  comprises a cylindrical body portion  53  and a domed top  54 . The height of weight cam  52  is adjustable and the height selected for weight cam  52  determines how far lower punch  28  is pushed upwardly when punch head  32  of lower punch  28  hits weight cam  52 . The height of weight cam  52  is selected such that punch stem  38  of lower punch  28  moves upwardly in bore  44  of die  40  to push out of die  40  the excess amount of the mixture where the upper punch enters for forming the miniature tablet. For example, for forming a miniature tablet  16  of 5 mg, the overfill amount of 2 mg to 3 mg of the filled amount of 7 mg to 8 mg is pushed out of bore  44  of die  40  leaving the desired 5 mg in bore  44  of die  40 . Filling die  40  with more tablet mixture than is needed and then subsequently pushing out the excess amount before miniature tablet  12  is formed provides a more consistent weight of miniature tablet  12 .  
     [0051] Referring to FIG. 9, scraper bar  56  is positioned flush with the upper surface of central turret portion  16   c  and scrapes of excess tablet mixture which has been pushed out of die  40  caused by lower punch  28  engaging weight cam  52 . The excess tablet mixture scraped off by scraper bar  56  is directed by scraper bar  56  to trowel  57  for collection and re-use.  
     [0052] While the station is in weight adjustment area  50 , upper punch  68  is directed by cams to remain spaced above and out of die  40 , as shown in FIG. 3.  
     [0053] Referring to FIG. 3, upon exiting weight adjustment area  50 , the station enters pull down area  58 . In pull down area  58 , pull down cam  60  directs lower punch  28  downwardly along pull down area  62  for moving lower punch downwardly in die  40 , as shown in FIG. 10. The mixture for forming the miniature tablet, is pulled down in bore  44  of die  40  by suction created by lower punch  28  moving downwardly in die  40  to prevent puffing of the mixture when the upper punch enters for forming the miniature tablet. Portion  64  of pull down cam  60  is positioned at a distance D2 from edge  65  of pull down cam  60  to limit the amount travel of pull down cam  60  in order to retain punch stem  38  within bore  44  of die  40 , thereby preventing the mixture for forming the miniature tablet from entering counterbore  42  of die  40 .  
     [0054] While the station is in pull down area  58 , upper punch  68  is directed by cams to remain spaced above and out of die  40 , as shown in FIG. 3.  
     [0055] Referring to FIG. 3, upon exiting pull down area  58 , the station enters tablet compression area  66  where the mixture for forming the miniature tablet is compressed into miniature tablet  12 . Tablet compression area  66  can comprise pre-compression area of a standard Riva Piccola press which has been modified in accordance with the present invention. It has been found that a force in the range of about 50 to about 2000 Newtons (N) used in compression area  66  is sufficient to form miniature tablet  12 . For example, a typical compression force for producing a 2 mm diameter miniature tablet  16  is about 200 Newtons.  
     [0056] In tablet compression area  66 , adjustable ramp  86  directs upper punch upwardly when punch head  32  of lower punch  28  engages the ramp, as shown in FIGS.  11 A- 11 B. The height of adjustable ramp  86  is adjustable to a selected height using height control mechanism  88 . The amount of compression force provided by lower punch is determined by the height set for adjustable ramp  86 . Raising the height of adjustable ramp  86  causes lower punch  28  to move upwardly farther into die  40  as lower punch  28  rides up adjustable ramp  86 , thereby increasing the amount of compression force provided by lower punch  28 . Lowering the height of adjustable ramp decreases upward movement of lower punch  28  as lower punch  28  rides up adjustable ramp  86 , thereby decreasing the amount of compression force provided by lower punch  28 . Height control of adjustable ramp  86  by height control mechanism  88  provides precise control of compression force settings for forming miniature tablets  12  of the present invention.  
     [0057] In tablet compression area  66 , upper punch  68  is directed by upper cam  70  downwardly into die  40  as lower cam  26  is directed by adjustable ramp  86  into die  40 , as shown in FIGS.  12 A- 12 C. Upper punch  68  comprises punch stem  80  positioned at lower end  78  of upper punch  68 . Punch stem  80  has a diameter which matches the diameter of punch stem  38  of lower punch  26 . Punch tip  82  at the end of punch stem  80  can have a cylindrical body portion to impart a convex shape to the upper side of the miniature tablets. Punch head  76  is positioned at upper end  74  of upper punch  68 . Lower portion has a cylindrical body for connecting punch stem  80  to punch head  76 . Punch head  76  can have a knob shape for engaging upper cam  70  and various other cams of tablet press apparatus  10 .  
     [0058] In tablet compression area  66 , punch head  32  of lower punch  26  moves upwardly along adjustable ramp  86  as punch head  76  of upper punch  68  moves downwardly along upper cam  70  for decreasing the distance D3 between punch stem  38  of lower punch  26  and punch stem  80  of upper punch, as shown in the progression of FIG. 12A to FIG. 12B. Additional movement of lower punch upwardly along adjustable ramp as punch head  76  of upper punch  68  moves downwardly along upper cam  70  further decreases the distance D3 between punch stem  38  of lower punch  26  and punch stem  80  of upper punch to provide the desired compaction, as shown in the progression of FIG. 12B to FIG. 12C. In the present invention, compression rollers  89  used in the prior art conventional Riva Piccola press shown in FIGS. 1 and 13 are disabled and all compression is performed in tablet compression area  66 .  
     [0059] Referring to FIGS. 1 and 3, the punch set of lower punch  26  and upper punch  68  enters tablet ejection area  90  for ejecting a formed miniature tablet  12  from die  40 . Lower punch  26  ejects formed miniature tablet from die  40  by lower ejection cam  94  extending punch stem  38  through the entire length of bore  44  as upper ejection cam  96  raises upper punch  68 . Miniature tablet  12  is removed from punch tip  39  of lower punch  26  by take-off plate  98  knocking off miniature tablet  12  from punch tip  39  of lower punch  26  as lower punch passes under take-off plate  98  without hitting take-off plate  98  in tablet take-off area  98 . As take-off plate  98  knocks the formed tablets off of each punch tip  39  of lower punches as successive stations pass by it, miniature tablets  12  are gradually forced to the beginning of take-off chute  100  and then fall down take-off chute  100  into collection bin  104 .  
     [0060] Referring to FIG. 3, upper punch  26  and lower punch  68  are directed into tablet fill area  14  to repeat another revolution through tablet fill area  14 , weight adjustment area  50 , pull down area  58 , tablet compression area  66 , ejection area  92  and tablet take-off area  98  to produce another miniature tablet.  
     [0061] As station exits pull down area  58  and enters tablet compression area  66 , head room plate  106  provides space such that punch head of upper punch  68  is not directed downwardly until it engages ramp of upper cam  70  when compression is used to form miniature tablet  16 , as shown in FIG. 14. Transducer  107  measures compression forces of upper punch  68  such that compression forces can be precisely controlled.  
     [0062] Transducers may be provided at various locations, such as compression, ejection cam  94  and take-off plate  99  to measure and monitor forces exerted at these locations. A computer (and monitoring software) can receive signals corresponding to forces registered by transducers  107  to ensure proper functioning of tablet press apparatus  12  to form inventive miniature tablet  12 . Tablet press apparatus  12  is provided with control mechanisms for starting and stopping tablet press apparatus  12  and setting the speed of rotation of turret  16 . A transducer may be connected to drive mechanism  17  connected to turret  16  to detect turret speed. Tablet press apparatus  10  can be operated at a speed to meet the requirements of production and tablet mixture. For example, tablet press apparatus can be operated at about 100 rotations per minute of turret  16 .  
     [0063] Referring to FIG. 15, tablet mechanical strength testing apparatus  130  can be used to test mechanical strength of formed miniature tablet  12 . Apparatus includes aperture  132  which has received miniature tablet  12  in base arm  134  for receiving miniature tablet  12 .  
     [0064] Moveable press arm  136  is pressed downwardly or rolled over miniature tablet  12  received in aperture  132  of base arm  134 . Load cell  138  monitors force applied by press arm  136  to break miniature tablet  12 .  
     [0065] In an alternate embodiment illustrated in FIGS.  16 - 18 , tablet press apparatus  110  includes lower punch  111  with modified body portion  112  to have a reduced diameter in comparison with the body portion of lower punch  26 . For example, body portion  112  of lower punch  111  can have a diameter of about 5 mm to about 7 mm which is significantly reduced for the diameter of about 19 mm to about 25 mm of lower punch  26 . Die  121  can have a reduced height in comparison to die  40 . The reduced diameter of body portion  112  and the die height is used to reduce the column effect of forces on punch stem  120  positioned at upper end  114  of lower punch  111 . Punch stem  120  can have similar dimensions as punch stem  38  of lower punch  26 , described above. Punch head  116  positioned at lower end  118  of lower punch  111  has a reduced diameter in comparison with punch head  32  of lower punch  26 . For example, punch head  116  can have a similar diameter as body portion  112  of lower punch  111 , as described above. Similar dimensions of the diameter of an upper punch can be used. For example, die  121  can have a height of about 10 mm in comparison to a height of 22 mm of die  40 . The reduction in size of the lower punch and upper punch allows more stations to be provided on turret  16  with a plurality of tablet fill area  14 , weight adjustment area  50 , pull down area  58 , tablet compression area  66 , ejection area  92  and tablet take-off area  98 , as shown in FIG. 17. For example, up to 35 stations can be used on a four-sided press in this embodiment to provide 840,000 tabs/min at 100 RPM revelation in comparison to 10 stations used in the conventional Riva Piccola press to provide 60,000 tabs/min. Because of reduced forces used for compression of miniature tablets  16 , frame  13  can be formed of a lighter weight material and smaller motor, such as a direct current motor can be used for powering tablet press apparatus  100 .  
     [0066] In accordance with the invention, conventional excipients and lubricants may be used in the tablet mixture, in addition to any desired drug to be incorporated into the miniature tablets. Typical or representative excipients and lubricants in the tablet mixture are as follows:  
                                                   Excipient   % by weight (typical range)                          MCC   0-60%           Free-flow or Fast-flow lactose   0-60%           Starch   0-20%           Magnesium Stearate   0-5%           Stearic Acid   0-5%           Talc   0-5%           Hydrophilic Polymers   0-95%                      
 
     [0067] In accordance with the invention, hydrophilic polymers may be used in the tablet mixture to form the inventive miniature tablets  11 , and exemplary of these polymers are those that interfere with the wet extrusion of the wet mass, e.g., cellulosic polymers, including hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC), gums, including xanthan gum, gum karaya, guar gum and locust gum, carrageenan, partially and fully pre-gellatized starches, gelatins, PVAP, acrylic acid based polymers, and mid-to-high levels of polyvinylporrolidone of different molecular weights, and sodium carboxymethylcellulose (NaCMC) (Cekol).  
     [0068] Preferably, the tablet mixture is micronized to facilitate flow of the tablet mixture into the tablet die, which is discussed in more detail below.  
     [0069] Typical of the drugs that may be incorporated into the tablet mixture to be formed into the inventive miniature tablets are the same drugs that may be incorporated into larger tablets, such as 350 mg tablets, 500 mg tablets, or higher. Further, the drugs include those that are being considered for layering onto non-pareils or are being considered for wet granulation/extrusion and spheronization.  
     [0070] Advantages  
     [0071] The invention has many advantages, which include:  
     [0072] 1) providing miniature tablets  12 ;  
     [0073] 2) providing a miniature drug delivery device that contains a uniform amount of drug and has a uniform weight;  
     [0074] 3) providing a drug delivery device having a size similar to non-pareils without the problem of drug content consistency sometimes found with non-pareils;  
     [0075] 4) providing miniature tablets  12  containing hydrophilic polymers;  
     [0076] 5) providing an inventive method that permits precise control in setting and monitoring compression forces; and  
     [0077] 6) providing an effective, efficient, and economic method of producing miniature tablets  12 .  
     [0078] It is to be understood that the above-described embodiments are illustrative of only a few of the many possible specific embodiments which can represent applications of the principles of the invention. Numerous and varied other arrangements can be readily devised in accordance with these principles by those skilled in the art without departing from the spirit and scope of the invention.