Abstract:
A caplet having press-fit gelatin capsule shell halves includes one or more dimples formed in one or both ends of the caplet shells, which significantly reduces the thickness of the gelatin which thereby dissolves more quickly, allowing the medicament to be rapidly released into the body&#39;s digestive system. In one embodiment of the invention, the closing pins used to press the conventional capsule shell halves onto a core include a raised projection for debossing the dimples. As holding blocks of a press-fit machine move to encapsulate a caplet, closing pins form compressed dimples in at least one or preferably both ends of the gelatin capsule shell as the shells are applied to the core.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims priority under 35 U.S.C. § 119(e) on U.S. Provisional Application No. 60/772,352 entitled PRESS-FIT RAPID RELEASE MEDICAMENT AND METHOD OF MANUFACTURE, filed on Feb. 10, 2006, by Ronald L. Perry, the entire disclosure of which is incorporated herein by reference. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    The present invention relates to a coated medicament which has one or more indentations formed in the coating to allow the coating to rapidly dissolve to release medicament contained therein and a method and apparatus for manufacturing such a medicament. 
         [0003]    Typically, medicaments, such as analgesics including, for example, aspirin, acetaminophen, ibuprofen, NSAIDS or the like, are sold in a variety of dosage forms. The medicament itself is typically formed in the shape of a compressed circular tablet or a caplet-shaped tablet which frequently is coated with a hypromellose and hydroxypropyl cellulose (HPC) coating, such as Opadry®. Consumer studies have shown that consumers prefer a gelatin coating for such medications to provide easier swallowing and a better mouth feel as compared to uncoated medicaments, even though the uncoated (except for an Opadry® coating almost universally employed) medicament provides a faster, more rapid release of the medication when swallowed. 
         [0004]    In order to accommodate the consumer desire for a gelatin-coated product, numerous techniques have been employed for gelatin coating medicament tablets. Such techniques include pan coating, dip coating, enrobing, and spray coating of gelatin onto a core, which can be circular conventional tablet shape, a caplet tablet shape, or any other desired shape for a swallowable medicament. When caplets are covered with gelatin shells, they can be press-fit or shrunk fit onto a core as, for example, shown by U.S. Pat. Nos. 5,415,868 and 5,824,338. 
         [0005]    A partially dip-coated product, such as disclosed in  FIG. 1B  of U.S. Pat. No. 5,234,099, provides gelatin coating on opposite ends of, for example, a caplet, but leaves a center band of the core exposed, thereby having the benefit and mouth feel of a gelatin-coated product while having a faster or more rapid release characteristic of an uncoated, less consumer-desirable dosage form. 
         [0006]    Another approach to the partial dip-coating of a caplet-shaped tablet is partial encapsulation by press-fitting shortened capsule halves onto the core of a caplet. Such construction is disclosed in pending PCT patent application entitled QUICK DISSOLVE CAPSULE AND METHOD OF MANUFACTURING, Application No. PCT/US2005/031962, filed on Sep. 8, 2005, and assigned to the Assignee of the present invention. Although this dosage form has the same benefits as the partially dip-coated medicament, namely, the ease of swallowing and preferable mouth feel, it requires the use of specially manufactured capsule shell halves, which are somewhat shorter than existing capsule shell halves employed in press-fit caplet manufacturing machines. The machines may also have to be modified to accommodate certain capsule shell halves. 
         [0007]    Thus, there remains a need for a unique dosage form which has the benefits of a press-fit gelatin-coated medicament and yet has the rapid release characteristics approaching that of an uncoated caplet. 
       SUMMARY OF THE INVENTION 
       [0008]    The gelatin covered core, method of manufacturing, and apparatus for manufacturing a gelatin covered core of the present invention satisfies this need by providing a caplet-shaped core having press-fit gelatin capsule shell halves which abut at their free ends when press-fit onto the core to completely encapsulate the core. The shell halves include one or more dimples formed in one or more ends of the caplet shells to significantly reduce the thickness of the gelatin. As a result, the gelatin in the dimpled area(s) dissolves more quickly, allowing the core material to be rapidly dissolved. When used for a medicament, the active ingredients are rapidly released into the body&#39;s digestive system upon swallowing. In one embodiment of the invention, the closing pins used to press-fit the conventional capsule gelatin shell halves onto a core include a raised projection. When the closing pins move to encapsulate a caplet, they form compressed dimples in at least one or preferably both ends of the gelatin capsule shell as the shells are applied to the core. The dimples have a significantly reduced gelatin thickness, which dissolves more quickly, allowing rapid release of the medicament in the area of the dimples. 
         [0009]    The press-fit equipment is modified, although the sequence of operation is substantially the same as existing press-fit sequences of operation. The press-fit machinery includes upper and lower closing pins which force-fit capsule shells onto a core held in a block with at least one of the upper and lower closing pins including a projection extending in a direction toward the medicament core along the longitudinal axis thereof. When the upper and lower pins compress the gelatin capsule shells onto the core, at least one dimple is formed in one end of the medicament. This significantly reduces the thickness of the gelatin at the location of the projection in the closing pin and ultimately in the completed caplet. In a preferred embodiment of the invention, both the upper and lower closing pins of the press-fit machine include raised projections for forming dimples on opposite ends of the gelatin shells press-fit onto the caplet core. In other embodiments, a plurality of dimples may be formed in each of the closing pins. 
         [0010]    Thus, the invention contemplates the provision of a press-fit gelatin covered medicament having a gelatin coating with at least one dimple formed in the coating to greatly reduce the thickness of the gelatin. In a preferred embodiment, the medicament is in the form of a caplet-shaped core having press-fit gelatin capsule shells forced thereon utilizing closure pins of a press-fit machine, wherein at least one of the pins includes a projection extending toward the core as the capsule shell is press-fit onto the core. The invention also contemplates the resultant medicament as well as specialized closure pins which include projections on a face of the pin engaging a gelatin capsule shell half and the method of manufacturing a medicament by forcing gelatin capsule shell halves over a caplet-shaped core while simultaneously forming dimples in an end of at least one of the capsule shells. 
         [0011]    These and other features, objects and advantages of the present invention will become apparent upon reading the following description thereof together with reference to the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0012]      FIG. 1  is a vertical cross-sectional view of a medicament embodying one embodiment of the present invention; 
           [0013]      FIG. 2  is a right end view of the medicament shown in  FIG. 1 , it being understood that the left end view is substantially the same; 
           [0014]      FIG. 3  is a greatly enlarged fragmentary view, taken in the encircled area III of  FIG. 1 ; 
           [0015]      FIG. 4  is a vertical cross-sectional view of one of the press-fit stations of a machine, showing the configuration of the closure pins employed in the manufacture of the medicament shown in  FIGS. 1-3 ; and 
           [0016]      FIG. 5  is an end view of one end of an alternative embodiment of the invention. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0017]    Referring initially to  FIG. 1 , there is shown a medicament  10  embodying the present invention and comprising a tablet having a caplet-shaped core  12  which is compressed by conventional equipment to form a core with suitable excipients and active ingredients. Core  12  may be any number of medicaments, such as analgesics including aspirin, ibuprofen, acetaminophen, and NSAIDS or any number of other medicaments, such as anesthetics, antiarthritics, antibiotics, anticoagulants, antidepressants, antidiabetic agents, antiemetics, antiflatulents, antifungals, antihistamines, anti-infective agents, anti-inflammatory agents, antispasmodics, antitussives, antivirals, appetite suppressants, bronchodilators, cardiovascular agents, central nervous system agents, central nervous system stimulants, decongestants, diuretics, expectorants, gastrointestinal agents, migraine preparations, motion sickness products, mucolytics, muscle relaxants, oral contraceptives, osteoporosis preparations, polydimethylsiloxanes, respiratory agents, sleep-aids, urinary tract agents, and mixtures of the above as active ingredients mixed with conventional excipients, including fillers, disintegrating agents, lubricants, sweetening agents and/or flavorants. The following are examples of preferred embodiments of medicament cores using either a super disintegrant or effervescent couple to assure the rapid release of the medicament when manufactured according to the teaching of this invention. 
         [0000]    
       
         
               
               
               
               
             
               
             
               
               
               
               
             
               
             
               
               
               
               
             
               
             
               
               
               
               
             
               
             
               
               
               
               
             
           
               
                   
                   
               
               
                   
                 Ingredients 
                 mg/tab 
                 % 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 EXAMPLE 1: 
               
             
          
           
               
                   
                 APAP Compap Course L 
                 555.500 
                 88.174603 
               
               
                   
                 (90% acetaminophen) 
               
               
                   
                 Copovidone S-630 
                 11.500 
                 1.825397 
               
               
                   
                 Crospovidone XL 
                 63.000 
                 10.000000 
               
             
          
           
               
                 EXAMPLE 2: 
               
             
          
           
               
                   
                 APAP Compap Course L 
                 555.500 
                 87.757 
               
               
                   
                 (90% acetaminophen) 
               
               
                   
                 Microcryst Cellulose 
                 14.500 
                 2.291 
               
               
                   
                 Crospovidone XL 
                 63.000 
                 9.953 
               
             
          
           
               
                 EXAMPLE 3: 
               
             
          
           
               
                   
                 APAP Compap Course L 
                 555.500 
                 81.811 
               
               
                   
                 (90% acetaminophen) 
               
               
                   
                 Microcryst Cellulose 
                 14.500 
                 2.135 
               
               
                   
                 Sod Bicarb #2 F-gran 
                 54.500 
                 8.027 
               
               
                   
                 Citric Acid Anhydrs 
                 54.500 
                 8.027 
               
             
          
           
               
                 EXAMPLE 4: 
               
             
          
           
               
                   
                 APAP Compap Course L 
                 555.500 
                 77.910 
               
               
                   
                 (90% acetaminophen) 
               
               
                   
                 Microcryst Cellulose 
                 14.500 
                 2.034 
               
               
                   
                 Crospovidone XL 
                 34.000 
                 4.769 
               
               
                   
                 Sod Bicarb #2 F-gran 
                 54.500 
                 7.644 
               
               
                   
                 Citric Acid Anhydrs 
                 54.500 
                 7.644 
               
               
                   
                   
               
             
          
         
       
     
         [0018]    The medicament  10  of the preferred embodiment of the invention includes a press-fit gelatin capsule shell  14  on one end and a press-fit gelatin capsule shell  16  at the opposite end, which shells  14  and  16  meet and are abuttingly joined tightly together along seam  15  so as to completely encapsulate the core  12  within the gelatin shells  14  and  16 . The gelatin shells initially have a moisture content of from about 15.5% to about 17% to allow the plasticity for the shells to be coupled to core  12 . During the press-fitting of the shells onto core  12  at the ends of each of the shells  14  and  16 , there is formed a dimple  18  in shell  14  and  19  in shell  16  which is formed by the machine and process described below. As used herein, dimple means a concave indentation or depression formed in the gelatin or other shell material which substantially reduces the cross-sectional thickness of the shell material. Substantially, reduction, as used herein, means from about 50% to about 0% of the original capsule shell thickness. 
         [0019]    As seen in  FIG. 3  in which dimple  19  is shown in greater detail, the thickness of gelatin shell  16  has a thickness T 1  of from about 0.020 inches to about 0.060 inches, while the thickness of the dimple formed in the gelatin shell is substantially thinner, shown by the dimension T 2  in  FIG. 3 , with a depth of the circular dimple  19  shown therein formed to a thickness T 2  of from about 0.001 mm to about 1 mm. The diameter D ( FIG. 2 ) of the circular dimple  19  can range from about 0.03 mm to about 0.15 mm for a typical 5 mm diameter capsule shell  16 . The dimensions of dimple  18  in the opposite end of one embodiment  10  of the medicament is substantially the same as dimple  19  shown in  FIGS. 2 and 3 . In the broadest form of the invention, the core  12 , which typically is a medicament  10 , may include only one dimple formed in one end of one of the capsule shell halves  14  or  16 , although it is preferable to provide, as shown in  FIG. 1 , dimples at each end of the medicament  10 . The dimples are formed by debossing the gelatin shells  14  and  16  during the press-fit manufacturing of the medicament, as illustrated in  FIG. 4 . 
         [0020]    In  FIG. 4 , there is shown the holding block  20  of a press-fit encapsulating machine which is commercially available and may be a machine such as a Zanasi 70C manufactured by Industria Macchine Automatiche (IMA). Block  20  represents one of several blocks which are rotated on a rotary turntable, with each block being slightly arcuately shaped and including, for example, eleven apertures, such as aperture  22  ( FIG. 4 ), for holding capsule shell halves, such as  14  and  16 , and core  12  therein in position for press-fitting the shell halves  14  and  16  over core  12  utilizing upper and lower closing pins  24  and  26 . Pins  24  and  26  move in a direction toward one another, as shown by arrows A and B in  FIG. 4 , with cylindrical aperture  22  in a direction along the longitudinal axis of the elongated capsule-shaped core  12 . 
         [0021]    The closure pins  24 ,  26  each include a generally cylindrical body  30  with a hemispherical depression  32  at the end which extends within aperture  22  and which engages the gelatin shells  14  and  16 . Formed in the bottom of the concave hemispherical end  32  in the embodiment shown is a convex generally hemispherical projection  34  in each of the closure pins  24  and  26 . During the press-fit operation, projections  34  engage the gelatin shells  14  and  16  forming dimples  18  and  19 , respectively, due to the opposing pressure of the closure pins against the shells and caplet core  12 . The pressure encountered is the standard pressure employed in the commercially available press-fit machine, and, as an example, the length of the combined strokes of the closure pins (depending on capsule size) ranges from about 0.756 inches to about 0.804 inches for a size 500 capsule. The closure pins, when fully engaged with the core, press-fit the capsule shell halves together to form the medicament shown in  FIG. 1  and plastically deform the gelatin shells at the ends to form dimples  18  and  19 , respectively, having a relatively thin cross section as compared to the remainder of the walls of shells  14  and  16 . When the medicament is swallowed, the reduced cross section thickness of the dimpled areas dissolve more quickly, allowing the gastric juices to dissolve the medicament contained in core  12  more quickly than a conventional press-fit gelatin caplet. Through tests, it has been discovered that the disintegration rate is generally less than about 90 seconds, which is significantly less than that of a conventional press-fit gelatin-shell covered caplet. 
         [0022]    If desired, a greater number of dimples  34  can be formed in the upper and lower closure pins  24  and  26  and anywhere from about 1 to about 5 is contemplated. Although the shape is preferably generally convex hemispherical, as shown by projection  34 , it is possible to provide other geometric configurations for the dimple-forming projections, including a generally pyramidal projection which would substantially reduce the dimension T 2  to approaching zero.  FIG. 5  shows a caplet-shaped medicament  10 ′ with a gelatin shell  16 ′ having such a plurality of dimples  19 ′ formed therein at an end of increase the dissolution rate. Each end of the medicament  10 ′ may include a greater or fewer number of such indentations, which can be of the same size as discussed above. 
         [0023]    The press-fit encapsulating machine  100  and its operation are well known, however, a brief description follows. The machine includes a turntable which rotates a plurality of somewhat arcuate shaped capsule holding blocks  20  ( FIG. 4 ) through multiple processing stations by the rotation of the turntable. The machine includes a lower cap inserting station which inserts a capsule shell half  16  ( FIG. 4 ) in the lower portion of each aperture  22  in each of the holding blocks  20 . Next, at tablet-loading stations, a caplet  12  is positioned into the upper end of each aperture  22  such that it aligns and at least partially extends within the open end of the lower capsule shell half  16 , as illustrated in  FIG. 4 . The machine also includes an upper shell half loading station, adjacent the tablet station, which inserts capsule shell half  14  into the open end of each of the apertures  22  in block  20  generally in alignment with and extending partially over the caplet  12 . The machine also includes a checking station which checks to determine that both capsule shell halves and caplets have been inserted into the apertures  22  in holding block  20 . Finally, the machine includes a closing station in which a plurality of upper closing pins  24  align with the apertures  22  in holding block  20  are brought downwardly into aperture  22  while aligned lower closing pins  26  are brought upwardly into the block  20 , as best illustrated in  FIG. 10 . As the turntable rotates, each of the stations operate sequentially to perform their particular task during encapsulation. The upper and lower closing pins are substantially the same as the conventional pins of the commercially available machine with the exception of the modification of the hemispherical ends of the upper and lower pins, as described above, to include centered projections  34  which form the dimples  18  and  19  at the ends of the capsule shell halves. 
         [0024]    It will become apparent to those skilled in the art that these and various modifications to the preferred embodiment and method of manufacturing the medicament of the invention as described herein can be made without departing from the spirit or scope of the invention as defined by the appended claims.