Patent Publication Number: US-2022226196-A1

Title: Closed-system drug-transfer devices for solid dosage forms

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     The present application claims priority from U.S. Provisional Application 62/854,132, filed May 29, 2019, and U.S. Provisional Application 62/882,716, filed Aug. 5, 2019, both of which are assigned to the assignee of the present application and incorporated herein by reference. 
    
    
     FIELD OF THE APPLICATION 
     The present invention relates generally to techniques for preparation of oral dosage forms. 
     BACKGROUND OF THE APPLICATION 
     A closed system drug transfer device (CSTD) is a drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system. 
     The U.S. National Institute for Occupational Safety and Health (NIOSH) has provided the following definitions of a closed system drug transfer device (CSTD):
         “a drug-transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system” (NIOSH 2004).   “A drug containment device is one that is both airtight and leakproof.”       

     Commercially available CSTDs for liquid dosage form products include the following: BD PhaSeal™ (Becton, Dickinson), Tevadaptor (Teva, Israel), Halo (Corvida, USA), ChemoClave (ICUmed, USA), Equashield II (Equashield, USA), and NeoShield® (JMS, Japan &amp; USA). 
     In some common techniques for liquifying solid drug forms, the solid drug form is crushed and diluted in a vessel open to the environment, which may cause the work environment to be contaminated with carcinogenic or teratogenic substances, which might expose and endanger the medical staff to hazardous substances in the course of their duties as providers of medical care. 
     SUMMARY OF THE APPLICATION 
     Embodiments of the present invention provide a closed transfer system for solid oral dosage forms, which is configured to crush and liquefy solid oral drugs, such as solid cytotoxic drugs. The system performs the crushing and liquefaction under full sealing conditions, without allowing release of solid, liquid, or gaseous forms of the drug to the external environment, which might jeopardize the health of the attending healthcare workers. They system also mechanically prevents the transfer of environmental contaminants into the system. 
     Typically, the system is designed for single use, in order to obviate the need for complex cleaning of the system between operations, and to prevent cross-contamination between different drugs. 
     There is therefore provided, in accordance with an application of the present invention, apparatus including a closed-system grinding syringe for liquefying and delivering a solid dosage form, the closed-system grinding syringe including: 
     a barrel, which is shaped so as to define (a) a lateral wall shaped so as to define a cylindrical inner surface, (b) a top barrel opening, and (c) a bottom barrel wall; 
     a fluid port disposed on the bottom barrel wall; 
     a plunger, which includes a (a) plunger shaft; (b) a plunger head shaped so as to define a bottom plunger wall shaped so as to define a lower surface; and (c) a plunger-head annular seal, wherein the plunger head is insertable into and moveable within the barrel such that (a) a portion of the barrel defines a closed-system syringe chamber between the bottom barrel wall and the lower surface of the bottom plunger wall, and (b) the plunger-head annular seal forms a plunger-head fluid-tight seal between an outer surface of the plunger head and the cylindrical inner surface of the barrel; 
     a barrel cap, which is (a) configured to be attachable to the top barrel opening so as to form a barrel-cap fluid-tight seal with the top barrel opening, and (b) shaped so as to define a cap opening through the barrel cap, wherein the plunger shaft is slidably disposed through the cap opening so as to form a plunger-head fluid-tight seal between the plunger shaft and a perimeter of the cap opening; 
     a solid-dosage-form support disc, which (a) is disposed below the bottom plunger wall so as to define a grinding compartment between the lower surface of the bottom plunger wall and an upper surface of the solid-dosage-form support disc, and (b) is shaped so as to define a plurality of holes through the solid-dosage-form support disc; and 
     a knob, 
     wherein the closed-system grinding syringe is configured such that when (a) the solid dosage form is disposed in the grinding compartment, (b) the plunger head is inserted into the barrel, and (c) the closed-system grinding syringe is oriented upright, upon activation of the knob, the grinding compartment grinds the solid dosage form to a powder and at least 75% of the powder passes through the plurality of holes into a portion of the closed-system syringe chamber below the solid-dosage-form support disc. 
     For some applications, the closed-system grinding syringe is non-electrical and is configured such that when (a) the solid dosage form is disposed in the grinding compartment, (b) the plunger head is inserted into the barrel, and (c) the closed-system grinding syringe is oriented upright, upon mechanical activation of the knob, the grinding compartment grinds the solid dosage form. 
     For some applications, the lower surface of the bottom plunger wall is shaped so as to define grinding protrusions. For some of these applications, the holes of the solid-dosage-form support disc are aligned with the grinding protrusions, such that the grinding protrusions at least partially enter respective holes when the solid-dosage-form support disc moves closer to the lower surface of the bottom plunger wall. Alternatively or additionally, for some of these applications, the grinding protrusions are bottom-plunger-wall grinding protrusions, and the upper surface of the solid-dosage-form support disc is shaped so as to define support-disc grinding protrusions, which are not aligned with the bottom-plunger-wall grinding protrusions. 
     For some applications, the upper surface of the solid-dosage-form support disc is shaped so as to define support-disc grinding protrusions. 
     For some applications, the closed-system grinding syringe is configured such that the knob is activated by rotation thereof. 
     For some applications, the plunger shaft has a smaller average outer diameter than does the plunger head. 
     For some applications, the plunger is non-integral with the barrel, and separable from and coupleable to the barrel during normal use of the closed-system grinding syringe. 
     For some applications, the barrel cap is fixed to the plunger such that the plunger shaft is slidably disposed through the cap opening and the plunger is not separable from the barrel cap during the normal use of the closed-system grinding syringe. 
     For some applications, the plunger-head annular seal includes an O-ring. 
     For some applications, the fluid port includes a valve. 
     For some applications, the closed-system grinding syringe is configured to move the lower surface of the bottom plunger wall and the upper surface of the solid-dosage-form support disc closer to each other as the grinding compartment grinds the solid dosage form. 
     For some applications, the closed-system grinding syringe is configured such that the lower surface of the bottom plunger wall does not rotate while the lower surface of the bottom plunger wall and the upper surface of the solid-dosage-form support disc move closer to each other as the grinding compartment grinds the solid dosage form. 
     For some applications, the closed-system grinding syringe is configured to move the upper surface of the solid-dosage-form support disc with respect to the cylindrical inner surface of the barrel as the grinding compartment grinds the solid dosage form. 
     For some applications, the closed-system grinding syringe is configured such that the upper surface of the solid-dosage-form support disc does not rotate during upward movement of the dosage-form support disc with respect to the cylindrical inner surface of the barrel. 
     For some applications: 
     the closed-system grinding syringe further includes:
         an axially-moveable shaft, which (a) is disposed partially within the plunger shaft, (b) forms a fluid-tight seal with an inner surface of the plunger shaft, (c) is connected to the solid-dosage-form support disc, (d) is rotationally-fixed with respect to the plunger shaft, and (e) is shaped so as to define an inner space having an internally-threaded wall; and   an externally-threaded stem, which is (a) disposed partially within the plunger shaft, (b) axially fixed with respect to the plunger shaft, and (c) connected to the knob, and       

     an external thread of the externally-threaded stem is mated with an internal thread of the internally-threaded wall, such that rotation of the externally-threaded stem in one rotational direction causes upward axial movement of the axially-moveable shaft with respect to the plunger shaft, which in turn moves the upper surface of the solid-dosage-form support disc upward with respect to the cylindrical inner surface of the barrel, causing the grinding compartment to grind the solid dosage form. 
     For some applications, the closed-system grinding syringe is shaped so as to define a liquid channel having (a) a first liquid-channel opening in fluid communication with the fluid port and (b) a second liquid-channel opening in fluid communication with the closed-system syringe chamber. 
     For some applications, the closed-system grinding syringe is shaped so as to define: 
     a liquid channel having (a) a first liquid-channel opening in fluid communication with the fluid port and (b) a second liquid-channel opening in fluid communication with the closed-system syringe chamber, and 
     a gas channel having a first gas-channel opening in fluid communication with the fluid port. 
     For some applications: 
     the barrel is shaped so as to define an upper compartment between the barrel cap and the bottom plunger wall, when the barrel cap is attached to the top barrel opening, wherein the upper compartment is fluid-isolated from the closed-system syringe chamber and the external environment, 
     the liquid channel has a second liquid-channel opening in fluid communication with the closed-system syringe chamber through the bottom barrel wall, and 
     the gas channel has a second gas-channel opening in fluid communication with the upper compartment. 
     For some applications, at least a portion of the upper compartment is located within the plunger head. 
     For some applications, the liquid channel has a greater average inner diameter than does the gas channel. 
     For some applications, the grinding compartment is shaped so as to define one or more lateral openings for insertion of the solid dosage form into the grinding compartment. 
     For some applications, the one or more lateral openings are a single lateral opening that extends 360 degrees around the grinding compartment. 
     For some applications, the one or more lateral openings extend between 90 and 360 degrees around the grinding compartment. 
     For some applications, the fluid port is configured to mate with a tip of a syringe. 
     For some applications, the fluid port is shaped so as to define a female-taper fitting. 
     For some applications, the fluid port is configured to mate with a feeding tube. 
     For some applications, the feeding tube is selected from the group consisting of: a universal feeding tube, a percutaneous endoscopic gastrostomy (PEG) tube, a gastrostomy tube, and a nasogastric feeding tube. 
     For some applications, the apparatus further includes an adapter, which is configured to be sealingly coupled to the fluid port and to the feeding tube. 
     For some applications, the feeding tube is selected from the group consisting of: a universal feeding tube, a percutaneous endoscopic gastrostomy (PEG) tube, a gastrostomy tube, and a nasogastric feeding tube. 
     There is further provided, in accordance with an application of the present invention, a method of liquefying and delivering a solid dosage form, the method including: 
     providing a closed-system grinding syringe including:
         a barrel, which is shaped so as to define (a) a lateral wall shaped so as to define a cylindrical inner surface, (b) a top barrel opening, and (c) a bottom barrel wall;   a fluid port disposed on the bottom barrel wall;   a plunger, which includes (a) a plunger shaft; (b) a plunger head shaped so as to define a bottom plunger wall shaped so as to define a lower surface; and (c) a plunger-head annular seal;   a barrel cap, which is shaped so as to define a cap opening through the barrel cap, wherein the plunger shaft is slidably disposed through the cap opening so as to form a plunger-head fluid-tight seal between the plunger shaft and a perimeter of the cap opening;   a solid-dosage-form support disc, which (a) is disposed below the bottom plunger wall so as to define a grinding compartment between the lower surface of the bottom plunger wall and an upper surface of the solid-dosage-form support disc, and (b) is shaped so as to define a plurality of holes through the solid-dosage-form support disc; and   a knob;       

     inserting the solid dosage form into the grinding compartment; 
     thereafter, inserting the plunger head into the barrel such that (a) a portion of the barrel defines a closed-system syringe chamber between the bottom barrel wall and the lower surface of the bottom plunger wall, (b) the plunger-head annular seal forms a plunger-head fluid-tight seal between an outer surface of the plunger head and the cylindrical inner surface of the barrel; 
     thereafter, attaching the barrel cap to the top barrel opening so as to form a barrel-cap fluid-tight seal with the top barrel opening; 
     thereafter, while the closed-system grinding syringe is oriented upright, activating the knob such that the grinding compartment grinds the solid dosage form to a powder and at least 75% of the powder passes through the plurality of holes into a portion of the closed-system syringe chamber below the solid-dosage-form support disc; 
     thereafter, introducing a liquid into the closed-system syringe chamber via the fluid port; 
     thereafter, mixing the powder with the liquid to form a mixture; and 
     thereafter, delivering the mixture via the fluid port by moving the plunger head downward within the barrel. 
     For some applications, introducing the liquid into the closed-system syringe chamber via the fluid port including coupling a syringe to the fluid port and injecting the liquid from the syringe into the closed-system syringe chamber via the fluid port. 
     For some applications, the closed-system grinding syringe is configured to move the lower surface of the bottom plunger wall and the upper surface of the solid-dosage-form support disc closer to each other as the grinding compartment grinds the solid dosage form. 
     For some applications, the closed-system grinding syringe is configured such that the lower surface of the bottom plunger wall does not rotate while the lower surface of the bottom plunger wall and the upper surface of the solid-dosage-form support disc move closer to each other as the grinding compartment grinds the solid dosage form. 
     For some applications, the closed-system grinding syringe is configured to move the upper surface of the solid-dosage-form support disc with respect to the cylindrical inner surface of the barrel as the grinding compartment grinds the solid dosage form. 
     For some applications, the closed-system grinding syringe is configured such that the upper surface of the solid-dosage-form support disc does not rotate during upward movement of the dosage-form support disc with respect to the cylindrical inner surface of the barrel. 
     For some applications, activating the knob includes rotating the knob. 
     For some applications, the closed-system grinding syringe is shaped so as to define a liquid channel having (a) a first liquid-channel opening in fluid communication with the fluid port and (b) a second liquid-channel opening in fluid communication with the closed-system syringe chamber. 
     For some applications: 
     the closed-system grinding syringe is shaped so as to define (a) a liquid channel having (i) a first liquid-channel opening in fluid communication with the fluid port and (ii) a second liquid-channel opening in fluid communication with the closed-system syringe chamber, and (b) a gas channel having a first gas-channel opening in fluid communication with the fluid port, and 
     introducing the liquid into the closed-system syringe chamber via the fluid port includes coupling two needles of a dual-needle closed-pressure equalization syringe in fluid communication with the liquid channel and the gas channel, respectively, via the fluid port. 
     For some applications: 
     the barrel is shaped so as to define an upper compartment between the barrel cap and the bottom plunger wall, when the barrel cap is attached to the top barrel opening, wherein the upper compartment is fluid-isolated from the closed-system syringe chamber and the external environment, 
     the liquid channel has a second liquid-channel opening in fluid communication with the closed-system syringe chamber through the bottom barrel wall, and 
     the gas channel has a second gas-channel opening in fluid communication with the upper compartment. 
     For some applications, at least a portion of the upper compartment is located within the plunger head. 
     For some applications, the liquid channel has a greater average inner diameter than does the gas channel. 
     For some applications, the grinding compartment is shaped so as to define one or more lateral openings, and inserting the solid dosage form into the grinding compartment includes inserting the solid dosage form via the one or more lateral openings. 
     For some applications, delivering the mixture includes coupling the fluid port to a feeding tube and delivery the mixture to the feeding tube. 
     For some applications, the feeding tube is selected from the group consisting of: a universal feeding tube, a percutaneous endoscopic gastrostomy (PEG) tube, a gastrostomy tube, and a nasogastric feeding tube. 
     For some applications, delivering the mixture includes sealingly coupling an adapter to the fluid port and to the feeding tube. 
     For some applications, the feeding tube is selected from the group consisting of: a universal feeding tube, a percutaneous endoscopic gastrostomy (PEG) tube, a gastrostomy tube, and a nasogastric feeding tube. 
     There is still further provided, in accordance with an application of the present invention, apparatus including a closed-system grinding syringe for liquefying and delivering a solid dosage form, closed-system grinding syringe including: 
     a barrel, which is shaped so as to define (a) a lateral wall shaped so as to define a cylindrical inner surface, (b) a top barrel opening, and (c) a bottom barrel wall; 
     a fluid port disposed on the bottom barrel wall; 
     a plunger, which includes (a) a plunger shaft; (b) a plunger head shaped so as to define a bottom plunger wall shaped so as to define a lower surface; and (c) a plunger-head annular seal, wherein the plunger head is insertable into and moveable within the barrel such that (a) a portion of the barrel defines a closed-system syringe chamber between the bottom barrel wall and the lower surface of the bottom plunger wall, and (b) the plunger-head annular seal forms a plunger-head fluid-tight seal between an outer surface of the plunger head and the cylindrical inner surface of the barrel; 
     a grinding compartment; and 
     a knob, 
     wherein the closed-system grinding syringe is configured such that when (a) the solid dosage form is disposed in the grinding compartment, (b) the plunger head is inserted into the barrel, and (c) the closed-system grinding syringe is oriented upright, upon activation of the knob, the grinding compartment grinds the solid dosage form to a powder, and 
     wherein the closed-system grinding syringe is shaped so as to define:
         a liquid channel having (a) a first liquid-channel opening in fluid communication with the fluid port, and   a gas channel having (a) a first gas-channel opening in fluid communication with the fluid port.       

     For some applications, the liquid channel has a greater average inner diameter than does the gas channel. 
     For some applications, the closed-system grinding syringe further includes a barrel cap, which is configured to be attachable to the top barrel opening so as to form a barrel-cap fluid-tight seal with the top barrel opening. 
     For some applications: 
     the barrel is shaped so as to define an upper compartment between the barrel cap and the bottom plunger wall, when the barrel cap is attached to the top barrel opening, wherein the upper compartment is fluid-isolated from the closed-system syringe chamber and the external environment, 
     the liquid channel has a second liquid-channel opening in fluid communication with the closed-system syringe chamber through the bottom barrel wall, and 
     the gas channel has a second gas-channel opening in fluid communication with the upper compartment. 
     For some applications, at least a portion of the upper compartment is located within the plunger head. 
     For some applications, the barrel cap is shaped so as to define a cap opening through the barrel cap, and the plunger shaft is slidably disposed through the cap opening so as to form a plunger-head fluid-tight seal between the plunger shaft and a perimeter of the cap opening. 
     For some applications, the closed-system grinding syringe further includes a solid-dosage-form support disc, which (a) is disposed below the bottom plunger wall such that the closed-system syringe chamber defines the grinding compartment between the lower surface of the bottom plunger wall and an upper surface of the solid-dosage-form support disc, and (b) is shaped so as to define a plurality of holes through the solid-dosage-form support disc. 
     For some applications, the closed-system grinding syringe is configured such that when (a) the solid dosage form is disposed in the grinding compartment, (b) the plunger head is inserted into the barrel, and (c) the closed-system grinding syringe is oriented upright, upon activation of the knob, the grinding compartment grinds the solid dosage form to the powder and at least 75% of the powder passes through the plurality of holes into a portion of the closed-system syringe chamber below the solid-dosage-form support disc. 
     The present invention will be more fully understood from the following detailed description of embodiments thereof, taken together with the drawings, in which: 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic cross-sectional illustration of a closed-system grinding syringe for liquefying and delivering a solid dosage form, in accordance with an application of the present invention; 
         FIGS. 2A-B  are exploded schematic illustrations showing components of the closed-system grinding syringe of  FIG. 1 , in accordance with an application of the present invention; 
         FIG. 3  is a schematic cross-sectional view of the closed-system grinding syringe of  FIG. 1 , in accordance with an application of the present invention; 
         FIGS. 4A-L  are schematic illustrations of a method of using the closed-system grinding syringe of  FIG. 1  for liquefying and delivering a solid dosage form, in accordance with an application of the present invention; 
         FIG. 5  is a schematic illustration of another closed-system grinding syringe for liquefying and delivering a solid dosage form, in accordance with an application of the present invention; 
         FIGS. 6A-B  are schematic illustrations of a portion of a method of using the closed-system grinding syringe of  FIG. 5  for liquefying and delivering the solid dosage form, in accordance with an application of the present invention; 
         FIGS. 7A-C  are schematic illustrations of alternative configurations of components of the closed-system grinding syringe of  FIG. 1  or  FIG. 5 , in accordance with an application of the present invention; and 
         FIGS. 8A and 8B  are schematic illustrations of a protrusion support and a solid-dosage-form support disc of the components of  FIGS. 7A-C , in accordance with respective applications of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF APPLICATIONS 
     Reference is made to  FIG. 1 , which is a schematic cross-sectional illustration of a closed-system grinding syringe  10  for liquefying and delivering a solid dosage form  20 , in accordance with an application of the present invention.  FIG. 1  also shows an adapter  90 , described hereinbelow. As used in the present application, including in the claims, “grinding” means reducing to a powder comprising small (e.g., fine) particles, as by pounding, crushing, or pulverizing. Typically, the particle size is less than 2 mm. 
     Reference is also made to  FIGS. 2A-B , which are exploded schematic illustrations showing components of closed-system grinding syringe  10 , in accordance with an application of the present invention. The components closed-system grinding syringe  10  may comprise a metal, such as stainless steel, and/or a polymer. 
     Reference is further made to  FIG. 3 , which is a schematic cross-sectional view of closed-system grinding syringe  10 , in accordance with an application of the present invention. Although not a component of closed-system grinding syringe  10 , solid dosage form  20  is shown in  FIGS. 1, 2A -B, and  3  for illustrating the operation of closed-system grinding syringe  10 . In particular, solid dosage form  20  is shown in  FIGS. 2A-B  to illustrate the eventual location of solid dosage form  20 ; solid dosage form  20  is of course not inserted into closed-system grinding syringe  10  during manufacture of closed-system grinding syringe  10 , but during use of the syringe by a healthcare worker after manufacture. 
     Typically, closed-system grinding syringe  10  comprises:
         a barrel  22 , which is shaped so as to define (a) a lateral wall  24  shaped so as to define a cylindrical inner surface  26 , (b) a top barrel opening  52 , and (c) a bottom barrel wall  28 ;   a fluid port  30  disposed on bottom barrel wall  28 ; and   a plunger  32 , which comprises (a) a plunger shaft  34 ; (b) a plunger head  36  shaped so as to define a bottom plunger wall  38  shaped so as to define a lower surface  40 ;   and (c) a plunger-head annular seal  42  (comprising, for example, an O-ring or another resiliently elastic seal).       

     Plunger head  36  is insertable into and moveable within barrel  22  such that (a) a portion of barrel  22  defines a closed-system syringe chamber  46  between bottom barrel wall  28  and lower surface  40  of bottom plunger wall  38 , and (b) that plunger-head annular seal  42  forms a plunger-head fluid-tight seal between an outer surface  44  of plunger head  36  and cylindrical inner surface  26  of barrel  22 . Typically, plunger shaft  34  and plunger head  36  are arranged such that downward motion of plunger shaft  34  moves plunger head  36  downward within barrel  22 . 
     For some applications, plunger  32  is non-integral with barrel  22 , and separable from and coupleable to barrel  22  during normal use of closed-system grinding syringe  10 .  FIG. 1  (as well as  FIGS. 4A-B ) shows plunger  32  separated from barrel  22 , while  FIG. 3  (as well as  FIGS. 4C-L ) shows plunger  32  coupled to barrel  22  with plunger head  36  inserted into barrel  22 . Alternatively, plunger  32  is integrated with barrel  22 , in which case closed-system grinding syringe  10  is typically provided with plunger  32  maximally withdrawn from barrel, such that access is provided to grinding compartment  62 , described hereinbelow. 
     Typically, plunger shaft  34  has a smaller average outer diameter than does plunger head  36 . 
     Typically, closed-system grinding syringe  10  further comprises a barrel cap  50 , which is configured to be attachable to top barrel opening  52  (such as by relative rotation) so as to form a barrel-cap fluid-tight seal with top barrel opening  52 . Barrel cap  50  is shaped so as to define a cap opening  54  through barrel cap  50 . Plunger shaft  34  is slidably disposed through cap opening  54  so as to form a plunger-head fluid-tight seal between plunger shaft  34  and a perimeter of cap opening  54  (such as by an annular seal  55 , e.g., an O-ring). Typically, barrel cap  50  is fixed to plunger  32  such that plunger shaft  34  is slidably disposed through cap opening  54  and plunger  32  is not separable from barrel cap  50  during the normal use of closed-system grinding syringe  10 . 
     Typically, closed-system grinding syringe  10  further comprises a solid-dosage-form support disc  60 , which is disposed below bottom plunger wall  38  so as to define a grinding compartment  62  between a lower surface  64  of bottom plunger wall  38  and an upper surface  66  of solid-dosage-form support disc  60 . (Solid-dosage-form support disc  60  is thus disposed within closed-system syringe chamber  46 .) Solid-dosage-form support disc  60  is shaped so as to define a plurality of holes  68  through solid-dosage-form support disc  60 . (Because of these holes  68 , solid-dosage-form support disc  60  does not meaningfully disturb the fluid continuity of closed-system syringe chamber  46 .) Typically, holes  68  have an average diameter of at least 1 mm (e.g., at least 2 mm), no more than 5 mm, and/or between 1 mm (e.g., 2 mm) and 5 mm, and/or an average cross-sectional area of at least 0.8 cm2 (e.g., at least 3.1 mm2), no more than 20 mm2, and/or between 0.8 mm2 (e.g., 3.1 mm2) and 20 mm2. 
     Typically, grinding compartment  62  is shaped so as to define one or more lateral openings  86  for insertion of solid dosage form  20  into grinding compartment  62  (insertion of plunger head  36  into barrel  22  typically causes cylindrical inner surface  26  of barrel  22  to partially or entirely obstruct the one or more lateral openings  86 ). For some applications, as shown, the one or more lateral openings  86  are a single lateral opening that extends 360 degrees around grinding compartment  62 . Alternatively, for some applications, the one or more lateral openings  86  extend between 90 and 360 degrees around grinding compartment  62 . Alternatively, grinding compartment  62  instead defines another type of opening, such as a door, window, or flap. 
     Typically, closed-system grinding syringe  10  further comprises a knob  70 . Typically, knob  70  is coupled to a top end of plunger shaft  34 . For some applications, closed-system grinding syringe  10  is configured such that knob  70  is activated by rotation thereof. As mentioned above, plunger shaft  34  and plunger head  36  are typically arranged such that downward motion of plunger shaft  34  moves plunger head  36  downward within barrel  22 ; typically, knob  70  and plunger shaft  34  are arranged such that downward motion of knob  70  moves down plunger shaft  34 , and thus plunger head  36 . Alternatively, for some applications, closed-system grinding syringe  10  is configured such that knob  70  is activated by axial movement of knob  70  (downward or upward) (configuration not shown). 
     For some applications, closed-system grinding syringe  10  is configured such that when (a) solid dosage form  20  is disposed in grinding compartment  62 , (b) plunger head  36  is inserted into barrel  22 , and (c) closed-system grinding syringe  10  is oriented upright (i.e., barrel cap  50  is disposed above bottom barrel wall  28 ), upon activation of knob  70 , grinding compartment  62  grinds solid dosage form  20  to a powder  71  and at least 75% (e.g., at least 95%) of powder  71  passes through the plurality of holes  68  into a portion  92  of closed-system syringe chamber  46  below solid-dosage-form support disc  60 . 
     For some applications, lower surface  40  of bottom plunger wall  38  is shaped so as to define grinding protrusions  72 . For example, grinding protrusions  72  may comprise teeth, burrs, or an abraded surface. A protrusion support  81  may be provided that is shaped so as to define grinding protrusions  72 , and to couple grinding protrusions  72  to plunger head  36 , such that protrusion support  81  defines at least a portion of lower surface  40  of bottom plunger wall  38 . For some applications, lower surface  40  is shaped so as to define between 10 and 100 grinding protrusions  72 . Alternatively or additionally, for some applications, upper surface  66  of solid-dosage-form support disc  60  is shaped so as to define support-disc grinding protrusions, such as describe hereinbelow with reference to  FIGS. 7A-C  and  8 A-B. 
     Typically, closed-system grinding syringe  10  is non-electrical and is configured such that when (a) solid dosage form  20  is disposed in grinding compartment  62 , (b) plunger head  36  is inserted into barrel  22 , and (c) closed-system grinding syringe  10  is oriented upright, upon mechanical activation of knob  70 , grinding compartment  62  grinds solid dosage form  20 . 
     For some applications, fluid port  30  comprises a valve  93 . For example, the valve may comprise one or more self-sealing membranes, e.g., comprising silicone, rubber, or any other suitable materials for scaling. 
     For some applications, closed-system grinding syringe  10  is configured to move lower surface  40  of bottom plunger wall  38  and upper surface  66  of solid-dosage-form support disc  60  closer to each other as grinding compartment  62  grinds solid dosage form  20 . For example, closed-system grinding syringe  10  may be configured to move upper surface  66  of solid-dosage form with respect to cylindrical inner surface  26  of barrel  22  as grinding compartment  62  grinds solid dosage form  20 . 
     For some applications, closed-system grinding syringe  10  further comprises:
         an axially-moveable shaft  94 , which (a) is disposed partially within plunger shaft  34 , (b) forms a fluid-tight seal with an inner surface  48  of plunger shaft  34  (such as by an annular seal  56 , e.g., an O-ring), (c) is connected to solid-dosage-form support disc  60 , such as by one or more connection arms  96 , e.g., three connection arms  96 , (d) is rotationally-fixed with respect to plunger shaft  34 , and (e) is shaped so as to define an inner space having an internally-threaded wall  98 ; and   an externally-threaded stem  99 , which is (a) disposed partially within plunger shaft  34 , (b) axially fixed with respect to plunger shaft  34 , and (c) connected to knob  70 . The external thread of externally-threaded stem  99  is mated with the internal thread of internally-threaded wall  98 , such that rotation of externally-threaded stem  99  in one rotational direction (e.g., clockwise) (such as by rotation of knob  70 ) causes upward axial movement of axially-moveable shaft  94  with respect to plunger shaft  34 , which in turn moves upper surface  66  of solid-dosage-form support disc  60  upward with respect to cylindrical inner surface  26  of barrel  22 , causing grinding compartment  62  to grind solid dosage form  20  by squeezing and squashing solid dosage form  20  between upper surface  66  of solid-dosage-form support disc  60  and lower surface  40  of bottom plunger wall  38 . It is noted that a relatively large amount of force is applied to solid dosage form  20  by this rotational arrangement. Typically, closed-system grinding syringe  10  is configured such that upper surface  66  of solid-dosage-form support disc  60  and lower surface  40  of bottom plunger wall  38  can come very close to each other, typically touch each other, if not blocked by remnants of solid dosage form  20  that fail to pass through holes  68 .       

     Typically, upper surface  66  of solid-dosage-form support disc  60  does not rotate during upward movement of solid-dosage-form support disc  60  with respect to cylindrical inner surface  26  of barrel  22 , i.e., is rotationally fixed with respect to lower surface  40  of bottom plunger wall  38  and with respect to cylindrical inner surface  26  of barrel  22  (as well as with respect to other components of closed-system grinding syringe  10 ). In addition, lower surface  40  of bottom plunger wall  38  typically does not rotate while lower surface  40  of bottom plunger wall  38  and upper surface  66  of solid-dosage-form support disc  60  move closer to each other as grinding compartment  62  grinds solid dosage form  20  by squeezing and squashing solid dosage form  20  between upper surface  66  of solid-dosage-form support disc  60  and lower surface  40  of bottom plunger wall  38 ; i.e., lower surface  40  of bottom plunger wall  38  is rotationally fixed with respect to upper surface  66  of solid-dosage-form support disc  60  (as well as with respect to other components of closed-system grinding syringe  10 ). 
     For example, axially-moveable shaft  94  may be rotationally-fixed with respect to plunger shaft  34  by one or more set screws  58  that engage one or more corresponding axial depressions  59  defined by an outer surface of axially-moveable shaft  94 . Alternative ways of rotationally fixing axially-moveable shaft  94  with respect to plunger shaft  34  will readily be apparent to those skilled in the art who have read the present application. 
     Reference is now made to  FIGS. 4A-L , which are schematic illustrations of a method of using closed-system grinding syringe  10  for liquefying and delivering solid dosage form  20 , in accordance with an application of the present invention. 
     The method begins with the receipt of closed-system grinding syringe  10  by the healthcare worker, optionally with plunger head  36  pre-inserted into barrel  22 . Alternatively, the syringe is packaged with plunger head  36  separate from barrel  22 . If plunger head  36  is received pre-inserted into barrel  22 , the healthcare worker removes plunger head  36  from barrel  22 . 
     As shown in  FIGS. 4A-B , the healthcare worker inserts solid dosage form  20  into grinding compartment  62 . For example, solid dosage form  20  may comprise one or more drug pills, drug capsule, or any other solid dosage form. 
     Thereafter, as shown in  FIG. 4C , the healthcare worker inserts (a) plunger head  36  into barrel  22  such that a portion of barrel  22  defines closed-system syringe chamber  46  between bottom barrel wall  28  and lower surface  40  of bottom plunger wall  38 , and (b) attaches barrel cap  50  to top barrel opening  52  so as to form a barrel-cap fluid-tight seal with top barrel opening  52 . Solid dosage form  20  is not yet ground into powder  71  at this step of the method. 
     Thereafter, as shown in  FIGS. 4D-G , while closed-system grinding syringe  10  is oriented upright, the healthcare worker activates knob  70  (such as by rotation) such that grinding compartment  62  grinds solid dosage form  20  to powder  71  and at least 75% (e.g., at least 95%) of powder  71  passes through the plurality of holes  68  into portion  92  of closed-system syringe chamber  46  below solid-dosage-form support disc  60 . 
     Thereafter, as shown in  FIGS. 4H-I , the healthcare worker introduces (e.g., injects) a liquid  73  into closed-system syringe chamber  46  via fluid port  30 . 
     For some applications, fluid port  30  is configured to mate with a tip of a syringe  75  (separate from closed-system grinding syringe  10 ), for introducing liquid  73  into closed-system syringe chamber  46  via fluid port  30 . For example, fluid port  30  may be shaped so as to define a female-taper fitting, such as a Luer lock or a Luer taper, as are known in the art. 
     Thereafter, as shown in  FIG. 4J , powder  71  is mixed with liquid  73  to form a mixture  77  (e.g., a solution or a suspension), such as by shaking closed-system grinding syringe  10 . It is noted that before mixing generally most of powder  71  is loose at the bottom of closed-system syringe chamber  46 , which facilitates mixing more readily than if, for example, powder  71  were crushed into a cake during the grinding process. Typically, during this mixing, all or a portion of powder  71  that may have remained above solid-dosage-form support disc  60  during grinding, as described hereinabove with reference to  FIG. 4G , is washed through holes  68  into portion  92  of closed-system syringe chamber  46  below solid-dosage-form support disc  60 . Optionally, after mixing, the healthcare worker again activates knob  70  such that grinding compartment  62  grinds any small remaining pieces of solid dosage form  20  to powder  71 , and then mixes again, such that essentially 100% of powder  71  (and thus solid dosage form  20 ) eventually passes through holes  68  into portion  92  of closed-system syringe chamber  46  below solid-dosage-form support disc  60 . 
     Thereafter, as shown in  FIGS. 4K-L , the healthcare worker delivers mixture  77  via fluid port  30  by moving plunger head  36  downward within barrel  22 . 
     For some applications, bottom barrel wall  28  is shaped as a funnel (typically a shallow funnel), similar to the bottom surface of conventional syringe chambers, in order to allow more thorough delivery of mixture  77  from barrel  22  to fluid port  30 . For some of these applications, the bottom surface of solid-dosage-form support disc  60  is slightly convex (e.g., inverse-funnel shaped), similar to the bottom surface of a conventional syringe plunger, in order to fit snugly into the funnel-shaped bottom barrel wall  28  and increase delivery of mixture  77  from barrel  22 . 
     For some applications, fluid port  30  is configured to mate with a feeding tube, for delivering mixture  77  via fluid port  30 . For example, the feeding tube may be a universal feeding tube, a percutaneous endoscopic gastrostomy (PEG) tube, a gastrostomy tube, or a nasogastric feeding tube. Alternatively, mixture  77  may be delivered the patient&#39;s mouth, without a feeding tube. In general, closed-system grinding syringe  10  may be useful for liquifying solid drug forms for patients who cannot swallow solid drugs. 
     For some applications, as shown in  FIGS. 1 and 4K -L, a system is provided that comprises closed-system grinding syringe  10  and adapter  90 , which is configured to be sealingly coupled to fluid port  30  and to a feeding tube. For example, the feeding tube may be a universal feeding tube, a percutaneous endoscopic gastrostomy (PEG) tube, a gastrostomy tube, or a nasogastric feeding tube. Alternatively, mixture  77  may be delivered the patient&#39;s mouth, without a feeding tube. 
     Reference is again made to  FIG. 3 . For some applications, closed-system grinding syringe  10  is shaped so as to define:
         a liquid channel  74  having (a) a first liquid-channel opening  76  in fluid communication with fluid port  30  and (b) a second liquid-channel opening  76  in fluid communication with closed-system syringe chamber  46 , and   a gas channel  78  having (a) a first gas-channel opening  80  in fluid communication with fluid port  30 .       

     Optionally, liquid channel  74  has a greater average inner diameter than does gas channel  78 . 
     For some applications, barrel  22  is shaped so as to define an upper compartment  82  between barrel cap  50  and bottom plunger wall  38 , at least when barrel cap  50  is attached to top barrel opening  52 . Upper compartment  82  is fluid-isolated from closed-system syringe chamber  46  and from the external environment. For some applications, at least a portion of (e.g., an entirety of) upper compartment  82  is located within plunger head  36 . 
     For some applications, second liquid-channel opening  76  of liquid channel  74  is in fluid communication with closed-system syringe chamber  46  through bottom barrel wall  28 , and gas channel  78  has a second gas-channel opening  84  in fluid communication with upper compartment  82 . 
     Providing liquid channel  74  and gas channel  78  enables, for the introduction of liquid  73  into closed-system syringe chamber  46  via fluid port  30  described hereinabove with reference to  FIGS. 4H-I , the mating of fluid port  30  with a tip of a dual-needle closed-pressure equalization syringe comprising needles  79 A and  79 B, such that two needles of the dual-needle closed-pressure equalization syringe are in fluid communication with liquid channel  74  and gas channel  78 , respectively, via fluid port  30 . For example, dual-needle closed-pressure equalization syringes are described in U.S. Pat. No. 9,999,569 to Kriheli, U.S. Pat. No. 8,196,614 to Kriheli, and US Patent Application Publication 2019/0060170 to Kriheli et al., all of which are incorporated hereby reference; and Equashield® for liquid oral dosage forms is commercially available from Equashield LLC, Port Washington, N.Y., USA). The use of a dual-needle closed-pressure equalization syringe allows the injection of liquid  73  from a liquid compartment of the dual-needle closed-pressure equalization syringe into liquid channel  74  and the simultaneous return of gas from gas channel  78  into a separate gas compartment in the dual-needle closed-pressure equalization syringe. 
     Reference is now made to  FIG. 5 , which is a schematic illustration of a closed-system grinding syringe  110  for liquefying and delivering solid dosage form  20 , in accordance with an application of the present invention. Reference is also made to  FIGS. 6A-B , which are schematic illustrations of a portion of a method of using closed-system grinding syringe  110  for liquefying and delivering solid dosage form  20 , in accordance with an application of the present invention. Other than as described hereinbelow, closed-system grinding syringe  110  may be identical to closed-system grinding syringe  10 , described hereinabove with reference to  FIGS. 1-4L , may be used in the same manner, and may implement any of the features thereof described herein. 
     Unlike closed-system grinding syringe  10 , closed-system grinding syringe  10  is not shaped so as to define gas channel  78 . Instead of introducing liquid  73  into closed-system syringe chamber  46  as described hereinabove with reference to  FIGS. 4H-I , the healthcare worker introduces (e.g., injects) liquid  73  into closed-system syringe chamber  46  via fluid port  30  by mating a tip of a single-channel syringe  175  (which is separate from closed-system grinding syringe  10 , and is typically conventional). For example, fluid port  30  may be shaped so as to define a female-taper fitting, such as a Luer lock or a Luer taper, and syringe  175  may be shaped so as to define a male-taper fitting, such as a Luer lock or a Luer taper, as are known in the art. It is noted that the air in closed-system syringe chamber  46  prior to introduction of liquid  73  is sufficiently compressible such that the force necessary to introduce liquid  73  can be readily applied manually by the healthcare worker. 
     Reference is now made to  FIGS. 7A-C , which are schematic illustrations of alternative configurations of components of closed-system grinding syringe  10  or  110 , in accordance with an application of the present invention. Reference is also made to  FIGS. 8A and 8B , which are schematic illustrations of a protrusion support  281  and a solid-dosage-form support disc  360 , in accordance with respective applications of the present invention. 
     In these configurations, protrusion support  281  is provided that is shaped so as to define grinding protrusions  272 , and to couple grinding protrusions  272  to plunger head  36 , such that protrusion support  281  defines at least a portion of lower surface  40  of bottom plunger wall  38 . In these configurations, protrusion support  281  replaces protrusion support  81 , described hereinabove with reference to  FIGS. 2A-B  and  3 . In these configurations, closed-system grinding syringe  10  comprises solid-dosage-form support disc  360 , instead of solid-dosage-form support disc  60 . Solid-dosage-form support disc  360  is shaped so as to define a plurality of holes  368  through solid-dosage-form support disc  360 . Holes  368  are aligned with respective grinding protrusions  272 , such that grinding protrusions  272  at least partially enter respective holes  368  when solid-dosage-form support disc  360  moves closer to lower surface  40  of bottom plunger wall  38  (and thus closer to grinding protrusions  272 ). This alignment can perhaps be best seen in  FIG. 7C , which is a bottom-view of support disc  360 , in which grinding protrusions  272  can be seen partially inserted into respective holes  368 . This alignment allows solid-dosage-form support disc  360  to move close to protrusion support  281  (and lower surface  40  of bottom plunger wall  38 ), thereby increasing the strength of grinding of solid dosage form  20 . For some applications, holes  368  have a diameter of at least 0.2 mm, no more than 0.6 mm, and/or between 0.2 and 0.6 mm, such as 0.4 mm. 
     Alternatively or additionally, for some applications, an upper surface  366  of solid-dosage-form support disc  360  is shaped so as to define support-disc grinding protrusions  370 , which are not aligned with (i.e., do not overlap with) grinding protrusions  272 , such that the two sets of grinding protrusions are interspersed with each other and increase the strength of grinding of solid dosage form  20 . Alternatively, solid-dosage-form support disc  360  is not shaped so as to define any grinding protrusions. 
     Typically, closed-system grinding syringe  10  is configured such that upper surface  366  of solid-dosage-form support disc  360  (including support-disc grinding protrusions  370 , if provided) and lower surface  40  of bottom plunger wall  38  (grinding protrusions  272 ) (lower surface  40  is defined at least in part by the lower surface of protrusion support  281 ) can come very close to each other, typically touch each other, if not blocked by remnants of solid dosage form  20  that fail to pass through holes  368 . 
     It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.