Method and apparatus for manufacturing micro tablet

Abstract

To provide a method and an apparatus for manufacturing a micro tablet from a precursor material, such as pharmaceutical powder.SOLUTION: Various embodiments provide methods including: compressing powder in order to form a compressed mass having a selected density; and repetitively compactifying the compressed mass in order to form a micro tablet by increasing the density of the compressed mass. Related method and apparatus are provided.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 62 / 776,826, filed December 7, 2018, which is hereby incorporated by reference in its entirety.

[0002] SUMMARY OF THE DISCLOSURE The embodiments herein relate to methods and devices for producing microtablets, and more particularly, to methods and devices for producing ingestible drug-bearing microtablets. [Background technology]

[0003] Although the development of new drugs for treating various diseases is expanding, many of such drugs, including bioactive compounds such as proteins, antibodies, and peptides, are limited in their application because they cannot be easily formed or encapsulated into solid form for oral delivery or other delivery forms. One of the difficulties in this field is that in the process of fabricating drugs, including proteins, peptides, or antibodies, into tablets or other solid forms, drug denaturation or other biological activity may be lost due to the destruction of the protein structure by the fabrication process. In this regard, many such proteins have complex internal structures that define their biological activity. The denaturation or other destruction of such structure may result in the inactivation of the drug or a significant decrease in the drug's biological activity. In this regard, in certain instances, fabrication processes such as molding, compression, milling, grinding, or encapsulation have been found to be problematic. Summary of the Invention [Problem to be solved by the invention]

[0004] Thus, there is a need for methods and machines for forming bioactive compounds, such as proteins, antibodies, and peptides, into microtablets for oral or other delivery to humans or other mammals without significant loss of the compounds' biological activity. [Means for solving the problem]

[0005] Embodiments of the present disclosure include improved systems and methods for producing microtablets from precursor materials, such as pharmaceutical powders. Various embodiments provide apparatus and methods for directing, collecting, and compressing the powder to form a compacted mass of a selected density, and repeatedly compacting the compacted mass to increase the density of the compacted mass and form the microtablets.

[0006] An aspect of the technology herein is an apparatus and method for producing microtablet pharmaceutical powders, incorporating a plurality of movable members variably positioned relative to a container and a cavity therein for inducing, collecting and / or compressing the powder into a compacted tablet form, and maintaining the integrity of the pharmaceutical powder components. In one embodiment, a first movable member is positioned relative to the container, and the first movable member may be moved from one position to its second position within the cavity to compress, compact, or otherwise collect or induce the pharmaceutical powder to form a collected mass of powder at a first location within the cavity. The inducing, compressing, or compacting by the first movable member may only act to collect the powder in a particular area of ​​the cavity, or, optionally, to increase the density of the pharmaceutical powder within the cavity, i.e., to have a first density.

[0007] Compacting can optionally include compressing the powder in a second direction within the cavity with a second movable member. Compacting or compacting with the second movable member can optionally serve to further increase the density of the pharmaceutical powder, i.e., to have a second density higher than the first density. Movement of the second movable member in the second direction can optionally be orthogonal to movement of the first movable member in the first direction.

[0008] Compression can optionally include compressing or compacting by a third movable member, which can optionally act to further increase the density of the pharmaceutical powder, i.e., to have a third density higher than the second density. Furthermore, the third movable member may further include a reciprocating member articulating in a third direction such that with successive reciprocating movements of each of the movable members, the density of the powder gradually increases to create a compacted solid mass at a final density and shape to form a microtablet according to the present technology. The third direction of movement of the third movable member can optionally be orthogonal to one or both of the directions of movement of the first movable member and the second movable member.

[0009] Further aspects of the technology described herein will be set forth in the following portions of the specification, the detailed description being intended to provide a complete disclosure of embodiments of the technology and not to impose limitations thereon.

[0010] The techniques described herein will be more fully understood by reference to the following drawings, which are presented by way of example only: [Brief description of the drawings]

[0011] [Figure 1] FIG. 1 is a perspective view of an embodiment of a system of the present technology for producing minitablets. [Diagram 2] FIG. 2 is a perspective view of an embodiment of a device for producing microtablets shown in the system of FIG. 1, the device being shown in a first position. [Diagram 3]FIG. 3 is an enlarged view of a portion of the device for producing microtablets shown in FIG. 2. [Figure 4] FIG. 3 is an exploded perspective view of the container of the device for producing microtablets shown in FIG. 2. [Diagram 5] 5 is an enlarged plan view of a portion of the device shown in FIG. 2 taken along line 5-5 of FIG. 4, illustrating the container and first, second and third movable members in slidable cooperation therewith. [Figure 6] 6 is a cross-sectional view of components of the device shown in FIG. 4 taken along line 6-6 of FIG. 5. [Figure 7] 6 is an enlarged detail view of a portion of the cross-sectional view of FIG. 4 taken along line 6-6 of FIG. 5. [Figure 8] FIG. 6 is a perspective view of a slide shown in the device illustrated in FIGS. 1 to 5. [Figure 9] FIG. 9 is a side view of the slide of FIG. 8. [Figure 10] 3 is an enlarged perspective view of a portion of the device of FIG. 2 in a second position. [Figure 11] 3 is an enlarged perspective view of a portion of the device of FIG. 2 in a third position. [Figure 12] FIG. 6 shows a cross-sectional view of the device of FIG. 2 in a third position. [Figure 13] FIG. 13 is an enlarged view of a portion of FIG. 12, with the device of FIG. 2 in a third position. [Figure 14] 3 is an enlarged perspective view of a portion of the device of FIG. 2 in a fourth position. [Figure 15] FIG. 3 is an enlarged perspective view of a portion of the device of FIG. 2 in a fifth position. [Figure 16] FIG. 3 is an enlarged perspective view of a portion of the device of FIG. 2 in a sixth position. [Figure 17] FIG. 2 is a perspective view of another embodiment of a system for producing microtablets of the present technology. [Figure 18] FIG. 18 is an enlarged view of a portion of the device for producing the microtablets of FIG. 17. [Figure 19] 19 is a cross-sectional view of the device for producing the microtablets of FIG. 17 taken along line 19-19 of FIG. 18. [Figure 20] 20 is a cross-sectional view of the device for producing the microtablets of FIG. 17 taken along line 20-20 of FIG. 18. [Figure 21] FIG. 2 is a perspective view of another embodiment of a system for producing microtablets of the present technology. [Figure 22] FIG. 22 is a side view of a device for producing the minitablets of FIG. 21. [Figure 23] FIG. 22 is a side view of the device for producing the microtablets of FIG. 21 in a second position. [Figure 24] 24 is a side view of the device for producing the microtablets of FIG. 21 taken along line 24-24 of FIG. 22. [Diagram 25] 25 is a cross-sectional view of the device for producing the microtablets of FIG. 21 taken along line 25-25 of FIG. 23. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Various embodiments of the present technology provide methods and devices, which may be referred to as apparatus or machines, for the fabrication and / or manufacture of microtablets. "Microtablets" are referred to herein as small structures having any of a number of suitable types or shapes, and may include or be referred to as tablets, pills, slugs, compressed or compacted masses, cylindrical masses, compressed or compacted cylindrical masses, microscale shaped masses, or any combination of the foregoing. In some embodiments, the microtablets may include or be formed from therapeutic compositions. Such therapeutic compositions may include any of a variety of therapeutic substances (also referred to as therapeutic agents), such as pharmacologically active substances (also referred to as medicines) for treating diseases or other conditions of the body, vaccines, cells (e.g., produced by or from a living organism, or containing components of a living organism), vitamins, minerals, or other nutritional supplements, or DNA or siRNA transcripts (e.g., for modifying genetic abnormalities, diseases, or disorders).

[0013] Examples of pharmacologically active agents may include, but are not limited to, peptides, proteins, immunoglobulins (e.g., antibodies), large molecules, small molecules, hormones, and biologically active variants and derivatives of any of the foregoing. In various embodiments, the therapeutic compositions may include various excipients known in the pharmaceutical arts.

[0014] The microtablets produced by the methods and machines of the present technology can be configured to be used in combination with any suitable drug delivery system and can be administered via an administration route appropriate for the condition to be treated. Such administration routes can optionally include, but are not limited to, oral, sublingual parenteral, intravenous, intramuscular, intraventricular, and intracardiac administration. For example, microtablets containing insulin can be taken orally and delivered to the small intestine, where the drug can be delivered to the wall of the small intestine or to surrounding tissues such as the peritoneal wall or cavity. In another example, microtablets containing insulin can be injected into subcutaneous tissue, for example intramuscularly, or otherwise placed so that they optionally dissolve and release insulin into the bloodstream.

[0015] In various embodiments, the microtablets may be formed by molding of a precursor material using the methods and machines described herein. The precursor material may include a therapeutic composition, and at least a portion of the biological activity (also referred to as bioactivity) of the therapeutic composition or constituent therapeutic agent is preserved after formation of the microtablet. The precursor material may optionally include excipients such as lubricants, binders, fillers, or disintegrants. In various embodiments, the manufacture of the microtablets may be achieved by compression or compaction of the precursor material, and the compression or compaction force is selected to minimize degradation of the biological activity of the drug. In various embodiments, the microtablets of the present technology may optionally have other characteristics, such as density or particle size, that may in some cases correlate with a minimum level of biological activity (also referred to as bioactivity herein) of the therapeutic composition or constituent therapeutic agent.

[0016] According to various embodiments, the biological activity of the therapeutic agent or composition may be correlated to the structural integrity of the therapeutic agent or composition after formation of the microtablets. Such correlation may be achieved, for example, by correlating results from a biological activity assay to a chemical assay, whereby a selected percentage of drug, for example, by weight, is maintained at the composition level after formation, compared to the percentage in the precursor material. As mentioned above, the therapeutic composition may optionally include a protein, peptide, or antibody, whose biological activity in the microtablets is at least 70% relative to before any compression or compaction during manufacture, for example, at least 90% relative to before any compression or compaction during manufacture, or at least 95% relative to before any compression or compaction during manufacture. These percentages may also correspond to the weight percentage of drug remaining in the microtablets, compared to the weight percentage in the precursor material, for example, by correlating biological activity assays to chemical assays for weight composition, as described above. The microtablets of the present technology optionally have a biological activity of about 1.00-1.15 mg / mm 3 , for example, about 1.02 to 1.06 mg / mm 3 The density can range from 0.01 to 0.01.

[0017] For convenience, the precursor material is described herein as being in the form of a powder. However, for any instance herein, it should be understood that the precursor material may instead be one of a powder, a liquid, a slurry, or a paste, or a mixture thereof. Additionally, the term "pharmaceutical powder" is sometimes used interchangeably herein with the term "powder."

[0018] According to various embodiments, the microtablets can optionally be configured to dissolve or otherwise degrade at a target site to release the therapeutic composition at the target site. Such a target site may correspond, for example, to a wall of a gastrointestinal organ (e.g., the small intestine wall) or to a surrounding tissue (e.g., a target site in the peritoneal wall or cavity). In additional or alternative embodiments, the target site may correspond to subcutaneous tissue, including muscle tissue, such as, for example, an arm, leg, or buttocks.

[0019] The microtablets may optionally be inserted into or otherwise incorporated into structures such as tissue-penetrating microneedles made from biodegradable materials. Suitable biodegradable materials may optionally include various sugars such as maltose and sucrose, various lactic acid polymers such as polyglycolic acid (PGA), polylactic acid (PLA), or polyglycolic lactic acid (PGLA), various polyethylenes, various celluloses such as HPMC (hydroxypropylmethylcellulose), PVOH (polyvinyl alcohol), silicone rubber, and other biodegradable polymers known in the art.

[0020] The materials and other properties of the microtablets and optional microneedles can optionally be selected to provide a designed degradation rate. For example, the degradation rate can optionally be t max , C max , t 1 / 2 The therapeutic agent can be designed to achieve various pharmacokinetic parameters, such as the dose, concentration, or area under the curve (AUC).

[0021] The therapeutic composition of the microtablets may include, by way of non-limiting example, a glucose-regulating protein such as insulin (e.g., human insulin and / or insulin produced using recombinant DNA methods) or an incretin such as GLP; an antibody such as an IgG or an antibody from the class of antibodies that inhibits TNF, such as adalimumab (HUMIRA), infliximab (Remicade), certolizumab pegol (Cimzia), golimumab (Simponi), or etanercept (Enbrel); and / or an interleukin-neutralizing protein such as an antibody that binds to another or an interleukin or its receptor (e.g., one or more of interleukins 1-36, e.g., interleukin 1, interleukin 17a, and their respective analogs and derivatives).

[0022] In many embodiments, the powder used to form the tablets is in the form of a lyophilized powder. Thus, the process of lyophilization is briefly described here. This description is for illustrative purposes only, and many variations of the process are possible. Lyophilization, also known as freeze-drying, is a process for preserving organic materials, including food, pharmaceuticals, and biological materials (cells, yeast, and antibodies). It includes three main stages or steps, including freezing, primary drying (also known as sublimation), and secondary drying (e.g., adsorption and / or desorption). In some cases, there may be a pre-treatment step prior to freezing.

[0023] Pretreatment includes any method of treating the material to be lyophilized prior to freezing. This may include collecting the material, modifying the formulation (i.e., adding excipients or other ingredients to increase stability, maintain appearance, and / or improve processing), reducing high vapor pressure solvents, or increasing surface area.

[0024] During the freezing step, the material is cooled below its triple point, the lowest temperature at which the solid, liquid, and gas phases of the material can coexist. This ensures that sublimation, rather than melting, occurs in the subsequent step. Larger ice crystals are preferred to promote faster, more efficient freeze-drying. Larger ice crystals form networks within the product that promote faster removal of water vapor during sublimation. To generate larger crystals, the product cum can be frozen slowly or cycled up and down in temperature in a process called annealing. Freeze-drying is easiest to achieve using large ice crystals, which can be generated by slow freezing or annealing. However, with biological materials such as living cells, if the crystals are too large, they can rupture the cell walls, which results in less than ideal freeze-drying results. To prevent this, freezing may be performed rapidly with a final temperature ranging from about -50°C (-58°F) to about -80°C (-112°F). For materials that tend to precipitate, annealing can be used, as described above.

[0025] In the second phase of freeze drying, primary drying (sublimation), the material is placed in a chamber, the pressure is reduced (to the range of a few hectopascals (a few millibars)) to create a partial vacuum, and sufficient heat is added to the chamber to sublimate (or go directly from the solid phase to the liquid phase) the frozen water contained in the frozen material. The amount of heat required can be calculated using the latent heat of sublimation of the sublimating molecules. The vacuum accelerates the sublimation process. Often, a cold condenser chamber and / or condenser plates may be used to provide a surface(s) for the water vapor to re-liquefy and / or solidify.

[0026] Approximately 95% of the water in the material is removed during the primary drying phase. Depending on the material, primary drying can be a slow process (e.g., on the order of several days) because if too much heat is used, it can change or degrade the structure of the material.

[0027] The final phase of freeze-drying is secondary drying (e.g., adsorption / desorption), during which the remaining water, ionically or otherwise bound to the material, is removed. This part of the freeze-drying process is governed by the adsorption isotherm of the material for bound water (e.g., ionically bound water). In this phase, the temperature is raised higher than in the primary drying phase, and may even exceed 0°C (32°F) to break the physicochemical interactions (e.g., ionic or other bonds) formed between the water molecules and the frozen material. Usually, the pressure is also reduced at this stage (usually in the microbar range, or a fraction of a pascal) to facilitate desorption. However, some products benefit from increased pressure. After the freeze-drying process is completed, the vacuum is usually broken with an inert gas, such as nitrogen, before the material is sealed. At the end of the run, the final residual moisture content of the product is small, about 1% to 4%.

[0028] The methods and machines of the present technology can optionally provide a list or plurality of microtablets, where a property of the microtablets, such as bioactivity of the therapeutic composition after formation and / or density of the microtablets, is substantially maintained within a selected range for substantially the entire list. Such methods and machines can advantageously maintain uniform dosage and pharmacokinetic parameters of one or more selected drugs of the microtablet embodiments of the present technology.

[0029] The microtablet embodiments of the present technology may be any of a number of suitable shapes, such as pellet-shaped or tablet-shaped, cone-shaped, cylinder-shaped, cube-shaped, spherical, or other similar shapes. The method, device, and apparatus for producing the microtablets of the present technology from a powder (e.g., from a pharmaceutical powder disclosed herein for consumption by humans or other mammals) may optionally include compressing, compacting, or pressing the powder to form a compressed mass of a certain density. The compressed mass may optionally be subsequently compacted to increase the density of the compressed mass. The compressing, compacting, or pressing may optionally be in the form of repeated compacting to increase the density of the compressed mass. In one or more embodiments, the compressed mass may be in the form of a cylinder or cylindrical shape and extends along a longitudinal axis. The compaction may be along the longitudinal axis, whether repeated or not. The compressed mass, e.g., a cylindrical compressed mass, may optionally be compacted or packed into a cylindrical mold or other forming area to form a microtablet. The methods and devices of the present technology can optionally be automated.

[0030] Compressing may optionally include feeding the powder through a funnel. Compressing may include compacting the powder in at least one direction to form a compacted mass. For example, compressing may include compacting the powder in a first direction and then compacting the powder in a second direction to form a compacted mass, where the second direction may optionally be orthogonal to the first direction. For another example, compressing may optionally include compacting the powder in a first, second, and third direction, which may be orthogonal to each other to form a microtablet. The compressing or compacting may be performed sequentially, simultaneously, or overlapping. Some or all of the compressing or compacting may be performed by a movable compacting member, respectively.

[0031] The methods, devices, and apparatus of the present technology can include providing material to a filling region and initiating an automated process that includes pushing the material from the filling region to a forming region, compressing the material in the forming region into a compressed mass having a perimeter that conforms to an inner surface of the forming region, and discharging the compressed mass from the forming region.

[0032] The examples of the present technology shown below are illustrative of the present technology and may be broader than the previous description of the present technology in some cases, but are nevertheless not intended to limit the scope of the previous description or the scope of the present technology. Additional features of the present technology shown in the following examples are optional. Features of the examples shown below can be combined with some or all of the previous description of the present technology, with or without other features of the examples shown below. All characteristics, steps, parameters, and features of any method, process, apparatus, device, machine, or system described below are not limited to the specific examples shown below, but instead are equally applicable to the previous description of the present technology and to all embodiments of the present technology disclosed herein. Rather than limiting the disclosure to specific terms or descriptions, broad terms and descriptions are sometimes replaced with more specific terms and descriptions for ease of explanation and understanding only.

[0033] The device, apparatus, or machine of the present technology can be of any suitable type, examples of which are shown in Figures 1-16. The machine 31 therein is shown as part of a system 32 that may optionally further include a controller 33 of any suitable type. In various embodiments, the controller 33 may correspond to or include one or more of a microprocessor (not shown) or an analog device, and combinations thereof. In some embodiments, the controller 33 includes a processor and application programming (not shown) in the form of machine-readable instructions or code stored in a memory (not shown) and executable on the processor to perform operations on the controller as detailed herein. The controller 33 may optionally include one or more knobs 170, a gauge 171, and a number of timers 172, 173 for controlling various operations of the machine 31 or system 32. The machine 31 may also be referred to as a microtabletting machine.

[0034] Machine 31 may optionally include a support structure 36, which may optionally include any suitable type of base 37. Base 37 may optionally include a bottom plate 38 and a top plate 39 that is joined to at least a portion of the top of bottom plate 38 by any suitable means, such as one or more suitable fasteners 41. Base 37, including portions thereof, may be formed from any suitable material, such as metal or plastic.

[0035] 3-7, the machine 31 may include a container 46 providing a cavity 47 for receiving the powder from which the microtablets are formed. A portion or the entirety of the cavity 47 may optionally be referred to as a filling area. The container 46 may be formed in any suitable manner and may optionally be formed as an assembly of parts / layers including a lower block 51, a middle plate 52, and an upper block 53 having a first end 53a and a second end 53b, as shown in FIG. 4, secured together by any suitable means, such as a plurality of any suitable fasteners (not shown). The middle plate 52 may be aligned with the lower block 51 and the upper block 53 by any suitable means, such as a plurality of locating pins 54 joined to the lower block 51 and extending upwardly from the lower block 51 in any suitable pattern for alignment or positioning with a respective plurality of openings 56 through the middle plate 52 and a respective plurality of holes or openings (not shown) extending into or through the upper block 53. The container 46, including its portions, may be formed from any suitable material, such as metal or plastic, and may be joined together and to the base 37 by any suitable means, such as a plurality of any suitable fasteners 57 (FIG. 5). In one embodiment, the middle plate 52 is optionally a mirror polished steel plate, which may be relatively easy to clean after contact with the pharmaceutical powder. It is understood that the container 46 may also be of unitary construction, formed from a single piece, portion, or component.

[0036] The cavity 47 may be of any suitable size and shape and may optionally be formed in one or more of the components of the container 46. With further reference to FIGS. 3-7, the cavity 47 may optionally include a cavity receiving portion 47a formed in the top block 53. The cavity receiving portion 47a may optionally be parallelepiped shaped and may be formed from an inner side surface 61 extending generally parallel to one another and an inner end surface 62 extending perpendicular to the inner side surface 61. Each of the inner side surface 61 and the inner end surface 62 may optionally be planar and may penetrate the top block 53 between the top and bottom surfaces of the top block 53. The cavity 47 may optionally include a cavity center portion 47b penetrating the middle plate 52 between the top and bottom surfaces of the middle plate 52. The cavity center 47b may optionally be rectangular in shape when viewed in plan, and may be formed from a first side 66 and an opposing second side 67 that extend generally parallel to one another on the middle plate 52 (FIG. 7). The second side 67 may optionally be coplanar with an inner end surface 62 of the cavity receiving portion 47a of the cavity 47, and the cavity center 47b of the cavity 47 may optionally have a length at least equal to the distance between the inner sides 61 of the cavity receiving portion 47a at the second end 53b of the upper block 53. Thus, the cavity center 47b may optionally be aligned with an end of the cavity receiving portion 47a, and the second side 67 of the cavity center 47b may optionally be flush with the inner end surface 61 of the cavity receiving portion 47a.

[0037] The cavity 47 may optionally include a cavity lower portion 47c below the cavity center portion 47b, which may optionally be at least partially formed from an elongated member 71. The elongated member 71 may optionally be tubular or cylindrical. The elongated member 71 may optionally be made from a polished steel tube, which may be relatively easy to clean after contact with the pharmaceutical powder. The elongated member 71 may be of any suitable diameter and length. In one embodiment, the elongated member 71 has a diameter of 0.7 millimeters, 0.5 millimeters, or less. In another embodiment, the elongated member 71 has a diameter of 0.25 millimeters or more. The elongated member 71 may optionally be secured between the lower block 51 and the middle plate 52 in any suitable manner. For example, it may be seated in a first slot 72 having a length extending across the width of the top of the lower block 51 and a second slot 73 having a length extending across the width of the bottom of the middle plate 52. Each of slots 72, 73 can receive elongate member 71 along at least a portion of the length of the slot and can optionally have a cross-sectional shape that matches the exterior cross-sectional shape of elongate member 71. For example, each of slots 72, 73 can optionally be arcuate in cross-section, e.g., have a semicircular cross-section.

[0038] The elongated member 71 may optionally be provided with an internal passageway 74 extending along the length of the elongated member 71. Additionally, the elongated member 71 may optionally have a notch 76 formed along a portion of the length of the elongated member 71. Such notch 76 may optionally be aligned with a bottom of the center cavity 47b formed in the middle plate 52. The internal passageway 74 may optionally have a cross-sectional dimension or diameter approximately equal to the width of the center cavity 47b. The notch 76 and the internal passageway 74 may be referred to as the lower cavity portion 47c.

[0039] The container 46 may optionally be referred to as including a variable funnel in that the shape and volume of the cavity 47 may change during use. For example, the volume of the path the powder travels from the introduction portion, through the cavity receiving portion 47a, the cavity center portion 47b, to the cavity lower portion 47c (e.g., the interior passageway 74 in the elongated member 71) decreases. Thus, the cavity 47 may be referred to as including a volume reduction region. Part or all of the container 46 may be referred to as a volume reduction chamber, a compaction chamber, a powder compression chamber, or any combination of the foregoing.

[0040] 1-12, the machine 31 may optionally include at least one movable component or member, such as a first movable member 81 slidably or movably supported by the support structure 36, e.g., by the container 46, and having an end surface 82 movable within the cavity receiving portion 47a to change the size and optionally the shape of the cavity receiving portion 47a (see, e.g., Figs. 3, 5, and 6). In this regard, for example, the first movable member 81 may be slidably or movable between a first or open position, e.g., shown in Fig. 6, in which the size of the cavity receiving portion 47a is relatively large, and a second or closed or compacted position, e.g., shown in Fig. 12, in which the size of the cavity receiving portion 47a is relatively small with a reduced volume. The first movable member 81, including any components thereof, may be made of any suitable material, such as metal or plastic.

[0041] A first movable member 81, which may be referred to as a guiding, compressing, or compacting component or member, or a plunger, is optionally held in place within the container 46 by the upper block 53. In this regard, for example, the first movable member 81 may be slidably disposed within an opening 83 provided in a first end 53a of the upper block 53 (FIG. 4). The opening 83 optionally has a width equal to the distance between opposing sides of the first movable member 81. An end face 82 (FIGS. 5, 6) of the first movable member 81 may optionally be dimensioned, sized, and shaped to slidably engage at least the side and bottom faces of the cavity receiving portion 47a and to prevent material within the cavity 47 from easily passing through the end face 82 during movement of the first movable member 81 from its first position to its second position. For example, end face 82 can optionally have a width equal to the distance between interior sides 61 of cavity receiving portion 47a, such that material in cavity 47 cannot easily pass between end face 82 and interior sides 61. First movable member 81 can optionally slide along the top of middle plate 52 in cavity receiving portion 47a, with a bottom edge of first movable member 81 at end face 82 slidably engaging the top of middle plate 52 to prevent material in cavity 47 from passing between end face 82 and middle plate 52.

[0042] The container 46 can optionally include a limiting surface 86 (FIG. 6) to limit the distance that the end face 82 of the first movable member 81 can travel within the cavity receiving portion 47a. For example, the first movable member 81 can include an upright portion 81a that engages with the limiting surface 86 of the upper block 53 at the opening 83, thereby limiting the movement of the first movable member 81 relative to the upper block 53. For example, when in its second position, the end face 82 of the first movable member 81 can optionally be spaced from the inner end face 62 of the cavity 47 to provide a gap or space between the end face 82 and the inner end face 62. Thus, the first movable member 81 can act to reduce the volume of the variable cavity 47. The upright portion 81a of the first movable member 81 can optionally serve as a handle for manually moving the first movable member 81 between its first and second positions. However, it will be appreciated that first movable member 81 may be moved or controlled automatically, for example by any suitable actuator or motor coupled to controller 33 or any other controller of system 32 .

[0043] The machine 31 may optionally include a second movable member 91 slidably or movably supported by the support structure 36, e.g., by the container 46, and movable within the cavity receiving portion 47a to change the size and optionally the shape of the cavity receiving portion 47a (see Figures 3, 6, and 12). In this regard, for example, the second movable member 91 may be slidably or movable between a first or open position, e.g., as shown in Figure 6, and a second or compacted position, e.g., as shown in Figure 12. The second movable member 91, including any multiple components forming the second movable member 91, may be made from any suitable material, such as metal or plastic.

[0044] A second movable member 91, which may be referred to as a guiding, compressing, or compacting component or member, or a compactor or plunger, is optionally held in place on the container 46 by the upper block 53, for example, on the second end 53b of the upper block 53. In this regard, for example, the second movable member 91 may have a carriage 91a joined to the compactor 91b by any suitable means. The carriage 91a may optionally be slidably disposed on the second end 53b of the upper block 53 by any suitable means, for example, by one or more guide posts 93 that may be slidably received in one or more alignment holes 94 (FIG. 5) extending upwardly through the carriage 91a. Thus, the carriage 91a may be movable upwardly and downwardly on the guide posts 93 to move the second movable member 91 between its first and second positions. The compactor 91b can be joined to the carriage 91a by any suitable means, such as a number of fasteners (not shown). The compactor 91b can be of any suitable shape, optionally in the form of a plate joined to one side of the carriage 91a and having a compacting portion 96 extending downwardly beyond the bottom of the carriage 91a. The compacting portion 96 can optionally have an end surface 97 that can be dimensioned, sized and shaped to slidably engage at least the inner side surface 61 and the inner end surface 62 of the cavity receiving portion 47a when the first movable member 81 is in its closed or compacting position, and to prevent any material within the cavity 47 from easily passing through the end surface 97 during movement of the compacting portion 96 from its first position to its second position. For example, end face 97 of compacting portion 96 can optionally have a width approximately equal to the distance between interior sides 61 of cavity receiving portion 47a and a thickness approximately equal to the distance between end face 82 of first movable member 81 and interior end face 62 of cavity receiving portion 47a when first movable member 81 is in its closed or compacted position. End face 97 moves downwardly between end face 82 and interior end face 62, as well as between interior sides 61.In one embodiment, the end surface 97 and the compacting portion 96 form a contact or interference fit between the end surface 82 and the inner end surface 62. Thus, any material within the cavity 47 cannot easily pass between the end surface 97 and the opposing inner side surface 61, inner end surface 62, and end surface 82 of the upper block 53 as the compacting portion 96 moves downward within the cavity receiving portion 47a toward its second or compacted position. The compacting portion 96 of the second movable member 91 optionally moves along the end surface 82 of the first movable member 81 as the compacting portion 96 advances to its second position, which is the compacting portion 96.

[0045] End surface 97 may have any suitable configuration, for example, planar or arcuate cross-section. End surface 97 may optionally be planar and perpendicular to the planar side of compactor 91b. End surface 97 may optionally be arcuate cross-section, for example, concave. Such concave end surface 97 may optionally have a radius approximately equal to the radius of interior passageway 74 of elongate member 71.

[0046] The upper block 53 may optionally include a limiter 101 to limit the distance that the end face 97 of the second movable member 91 travels within the cavity receiving portion 47a. In this regard, for example, the upper surface of the second end 53b of the upper block 53 may be or may include the limiter 101 that is engaged by the carriage 91a, thereby serving to define the second position of the compactor 91b. The second position of the end face 97 may be any suitable position within the receiving cavity portion 47a. For example, when the compactor 91b is in its second position, the end face 97 may optionally extend into the cavity center portion 47b within the middle plate 52. When the compactor 91b is in its second position, the end face 97 may optionally extend into the notch 76 or the internal passage 74 of the elongated member 71.

[0047] The second movable member 91 may optionally include a handle 91c, for example extending upwardly from one side of the carriage 91a, for manually moving the second movable member 91 between its first and second positions. However, it will be understood that the second movable member 91 may be moved or controlled automatically, for example by any suitable actuator or motor coupled to the controller 33 or any other controller of the system 32.

[0048] 1-15, and in particular, FIG. 8 and FIG. 9, the machine 31 can optionally include a mold 111 having a recess 112 for forming the microtablets of the present technology. The mold 111 can be referred to as a forming section, and the recess 112 can be referred to as a forming area. The machine 31 can optionally be configured such that the mold 111 receives compressed and / or compacted powder from the internal passage 74 of the elongated member 71. In this regard, for example, the machine 31 can include a mold carrier. The mold carrier can be of any suitable size and shape, and can be, for example, an elongated plate, such as a slide 113, made from any suitable material, such as metal or plastic. The slide 113 can be slidably supported by the support structure 36 between a first position, for example, shown in FIG. 14, and a second position, for example, shown in FIG. 15. The mold 111 can be, for example, formed integrally with the slide 113 from the same material as the slide 113, or can be formed from a different material from the slide 113 and secured within the slide. The mold 111 may optionally be cylindrical. The recess 112, which may be formed by the inner surface of the mold 111, may optionally be in the form of a cylinder, with openings on either side of the slide 113. The recess 112 may optionally have a width or diameter of 0.7 millimeters, for example 0.5 millimeters or less, to form microtablets of such dimensions. The recess 112 may optionally have a width or diameter of 0.25 millimeters or more, to form microtablets of such dimensions. The recess 112 may optionally have a length of 0.5 millimeters, 1.0 millimeters, or 10 millimeters, in combination with any of the aforementioned diameters, or any other suitable diameter, to form microtablets of selected dimensions. The recess 112 may optionally have a length and diameter or width that correspond to or are equal to the length and diameter or width of the microtablets being formed in the machine 31. The recess 112 may optionally have a length that is greater than the length of the microtablets being formed, for example, to form more than one microtablet in the recess 112.

[0049] The machine 31 may optionally include a track 116 for slidably receiving the slide 113 (FIG. 15). The track 116 may optionally be formed from the container 46 and at least one additional block 117, for example spaced from the container 46 by a distance approximately equal to the width of the slide 113. The additional block 117 may be fixed to the support structure 36 by any suitable means, for example by a number of fasteners 118 of any suitable type. When the slide 113 is in its first position, which may be referred to as a receiving position, one end of the recess 112 of the mold 111 is optionally aligned with the open end of the internal passage 74 of the container 46, and the other end of the recess 112 is closed, for example by the block 117. When the slide 113 is in its second position, which may be referred to as a discharge position, the recess 112 of the mold 111 is optionally accessible at both ends of the recess, for example on both sides of the slide 113. The slide 113 may be secured in one or both of its first and second positions by any suitable means, such as a first magnet 121 provided at one end of the slide 113 and a second magnet 122 (FIG. 9) provided at the other end of the slide. When the slide 113 is in its first position, the first magnet 121 optionally engages a third magnet 123 held to the support structure 36 by any suitable means, such as a first stop 126. When the slide is in its second position, the second magnet 122 optionally engages a fourth magnet 127 held to the support structure 36 by any suitable means, such as a second stop 128. The slide 113 may be optionally locked in one or both of its first and second positions by any suitable means, such as a locking mechanism 131 held to the support structure 36 by any suitable means. The locking mechanism 131 may be of any suitable type, such as a fixed clamp. An additional block 117 (not shown) may optionally be provided on the other side of the locking mechanism 131 in the y direction to provide support for the slide 113 when in the second position.

[0050] Slide 113 may optionally include a handle 132 ( FIG. 9 ), e.g., extending upwardly from the top of slide 113, for manually moving slide 113 between its first and second positions. It will be understood, however, that slide 113 may be moved or controlled automatically, e.g., by any suitable actuator coupled to controller 33 or any other controller of system 32.

[0051] The machine 31 may optionally include a third movable member 141 slidably or movably supported by the support structure 36, e.g., by the container 46 (see Figs. 2, 5, 14, and 15). The third movable member 141 may include a first end portion 141a and an opposite second end portion 141b having an end face 142 movable within the cavity 47, e.g., the cavity lower portion 47c, to change the size and optionally the shape of a portion of the cavity 47, e.g., the cavity lower portion 47c. In this regard, for example, the third movable member 141 may be slidably or movably between a first or retracted position, e.g., as shown in Fig. 5, in which the end face 142 is outside the cavity lower portion 47c, and a second or compacted position, e.g., as shown in Fig. 14, in which the end face 142 extends into at least the cavity lower portion 47c. The third movable member 141 may optionally be disposed within the first slot 72, and optionally within a first end of the internal passageway 74 of the elongate member 71, when in its first position. The third movable member may optionally be further disposed within the internal passageway 74, e.g., near a second end of the internal passageway 74 or within the recess 112, when in its second position.

[0052] The third movable member 141 can be any suitable size and shape, such as an elongated cylinder, rod, or pin extending along a longitudinal axis. The third movable member 141 can be referred to as a gauge pin, compression cylinder, rod or pin, compression or compaction component or member, plunger, compactor, reciprocating member, or reciprocating motion member, component, or compactor. The third movable member 141 can be made of any suitable material, such as hardened steel or another material that prevents bending of the movable member. The end surface 142 of the third movable member 141 can be any suitable shape, for example, a flat surface extending perpendicular to the longitudinal axis of the third movable member 141.

[0053] The third movable member 141 is optionally held in place on or within the container 46 by any suitable member or assembly. In this regard, for example, the first end portion 141a of the third movable member 141 may be supported by or joined to any suitable type of holder 143. The holder, which may be made of any suitable material, such as metal or plastic, may optionally be formed from one or more blocks or components slidably supported on one or more rails 144 supported by the support structure 36. The rails 144 may optionally be mounted by any suitable means on a support 146 joined to the base 37, e.g., the bottom plate 38. The holder 143 may optionally be referred to as a slide.

[0054] The third movable member 141 can optionally be moved or controlled automatically between its first and second positions, for example, by any suitable actuator or motor (not shown) coupled to the controller 33 or any other controller of the system 32. Such actuator can optionally be a pneumatic actuator having a port 147, each of which can be coupled to the controller 33 by a line 148 or any other suitable means. The actuator controlled by the controller 33 can move or reciprocate the third movable member 141 between its first and second positions at any suitable speed, rate, or frequency. The actuator can optionally control the pressure or force exerted by the end surface 142 of the third movable member 141 on the powder forming the microtablets of the present technology, including the duration of such pressure or force.

[0055] The machine 31 may optionally include an ejector 156 for, for example, displacing the compacted or cylindrical mass formed by the machine 31 from the recess 112 of the mould 111 when the slide 113 is in its second position (see Figures 15 and 16). The ejector 156 may be of any suitable type and may optionally include a pin 157 (Figure 3), which may optionally be cylindrical in shape. The pin 157 may have an end face 158. The cross section of the pin 157 may be no larger in cross-sectional size or shape than the cross section of the recess 112, and may be of the same cross-sectional size and shape as the recess 112. The ejector 156 may be supported in any suitable manner by the support structure 36, for example by the base 37.

[0056] The pin 157 may be movable between a first or retracted position, as shown, for example, in FIG. 15, in which the end face 158 is outside the recess 112, and a second or extended position, as shown, for example, in FIG. 16, in which the end face 158 is disposed at least partially through, disposed completely through, or penetrating the recess 112 to urge the compacted or cylindrical mass formed by the machine 31 out of the recess.

[0057] The ejector 156 can include a suitable actuator 161 (e.g., a motor) that can be coupled to the controller 33 or any other controller of the system 32 for moving the pin 157 between its first and second positions. Such actuator 161 can optionally be a pneumatic linear actuator having at least one port 162 coupled to the controller 33 by at least one line 163. The actuator 161 controlled by the controller 33 can move the pin 157 from its first position to its second position at any suitable speed. The actuator 161 can optionally control the pressure or force exerted by the end face 158 of the pin 157 on the powder forming the microtablets of the present technology, including the duration of such pressure or force.

[0058] The device, apparatus, or machine of the present technology may have other configurations. The machine 191 shown in Figures 17-20 may be included in a system 32, which may optionally further include a controller 33 or any other suitable controller. The machine 191, which may be referred to as a microtabletting machine, may optionally include a support structure 192 having a base, which may include a vertical plate 193. The support structure 192, including the vertical plate 193, may be formed from any suitable material, such as metal or plastic.

[0059] The machine 191 includes a container 196 with a cavity 197 for receiving pharmaceutical powder from which the microtablets of the present technology are formed. A portion or the entirety of the cavity 197 can optionally be referred to as a filling area. The container 196, including a portion thereof, can be formed from any suitable material, such as metal or plastic. The container 196 can be of any suitable type, can optionally be funnel-shaped, and can optionally include a first or top portion, referred to herein as a funnel 198. The funnel 198 can be formed from first and second sides, side components, or side portions 199, which can be joined by any suitable means. With reference to FIG. 19, an upright or vertical funnel 198, shown extending along the z-axis of FIG. 17, has an upper portion 198a and a lower portion 198b, which decrease in size and cross-sectional area or taper or narrow inwardly from the upper portion to the lower portion. Cavity receiving portion 197a is formed by a funnel having an upper opening 201 at the top of upper portion 198a for providing pharmaceutical powder to cavity receiving portion 197a and a smaller lower opening 202 at the bottom of lower portion 198b of funnel 198 for allowing pharmaceutical powder to exit cavity receiving portion 197a. Similar to funnel 198, cavity receiving portion 197a decreases in size and cross-sectional area or tapers or narrows inwardly from upper opening 201 to lower opening 202.

[0060] The container 196 optionally includes a container center 206 joined to a lower portion 198b of the funnel 198. The container center 206 may optionally be elongate and extend along a longitudinal axis aligned generally perpendicular to the funnel 198. For example, along a y-axis identified in FIG. 17, which is perpendicular to the z-axis of FIG. 17, and referring to FIG. 20, the container center 206 may have a first end portion 206a and an opposing second end portion 206b. Between the first end portion 206a and the second end portion 206b, the container center 206 has an elongate chamber extending longitudinally through the container center 206, which may be referred to as the cavity center 197b of the cavity 197. The cavity center 197b is formed from opposing first and second inner surfaces 207 and 208 of respective side walls 211, 212 of the container center 206 that extend generally parallel to one another. The container center 206 further includes a base plate for forming the bottom of the cavity center 197b. The base plate, referred to herein as a slide 213, seats flush with the bottom of the side walls 211, 212 to seal the bottom of the cavity center 197b against the side walls. The slide 213 is optionally disposed for slidable movement relative to the side walls 211, 212 in tracks 214 provided in a base block 216 of the support structure 192. The base block 216 may optionally be joined to the vertical plate 193 by any suitable means. The cavity center 197b may optionally be rectangular in shape, for example, when viewed from its end as in FIG. 19 and when viewed in plan as in FIG. 20. The cavity center 197b can optionally be referred to as cylindrical along its length between the first end portion 206a and the second end portion 206b, and can optionally be referred to as having a parallelepiped shape with a constant internal cross-sectional shape and area along its length (see Figures 19 and 20). The container center 206, for example at the first end portion 206a, is provided with an upper opening 217 that communicates with the lower opening 202 of the funnel 198 to allow material in the funnel-formed cavity receiving portion 197a to enter the cavity center 197b.

[0061] The cavity 197 may optionally include a cavity end portion 197c at the end of the cavity center 197b, which may optionally be at least partially formed from the elongated member 71. The elongated member 71 may have some or all of the configurations, materials, and other features discussed above with respect to the machine 31. The elongated member 71 may optionally be supported by the support structure 192 in any suitable manner, for example, in a slot 221 extending vertically along a surface 222 of an end block 223 joined to the second end portion 206b of the container center 206 by any suitable means. The slot 221 may receive the elongated member 71 along at least a portion of its length and may optionally have a cross-sectional configuration that follows the exterior cross-sectional configuration of the elongated member 71. For example, the slot 221 may optionally be of arcuate cross-section, for example of semicircular cross-section. The elongated member 71 may optionally be provided with an internal passage 74 extending along the length of the elongated member 71. Additionally, the elongate member 71 may optionally have a notch 76 formed along a portion of the length of the elongate member 71. The notch 76 may optionally be aligned with an end of the cavity center 197b formed in the second end portion 206b of the container center 206. The interior passageway 74 may optionally have a cross-sectional dimension or diameter approximately equal to the width of the cavity center 197b. The notch 76 and the interior passageway 74 may be referred to as the cavity end portion 197c.

[0062] Part or all of the container 196 may optionally be referred to as a variable funnel in that the shape of the cavity 197 may change during use, and similarly, the volume of the cavity 197 may change during use. For example, the volume of the passageway along which the pharmaceutical composition or powder travels from the entrance of the cavity 197, i.e., the entrance of the cavity receiving portion 197a, to the interior passageway 74 in the elongated member 71 at the cavity end portion 197c, decreases in volume along the path of such travel. Part or all of the cavity 197 may be referred to as a volume reduction region. Part or all of the container 196 may be referred to as a volume reduction chamber, a compaction chamber, a powder compression chamber, or any combination of the foregoing.

[0063] The machine 191 may optionally include at least one movable component or member that may be slidably or movably supported by a support structure 192, for example by a container 196, and may optionally include a first movable member 231 that may be movable within the cavity receiving portion 197a to vary the size and volume of the cavity receiving portion 197a (see FIG. 19). In this regard, for example, the first movable member 231 may be slidably or movable between a first or retracted position, for example shown in FIGS. 17-19, in which the size of the cavity receiving portion 197a is relatively large, and a second or extended or compacted position, not shown, in which the size of the cavity receiving portion 197a is relatively small with a reduced volume. The first movable member 231, including any components thereof, may be made from any suitable material, such as metal or plastic.

[0064] The first movable member 231 optionally includes a first end portion 231a and a second end portion 231b having an end surface 232. The first end portion 231a may be joined in any suitable manner to a connector block 233 coupled to a first actuator 236 (e.g., a motor) of any suitable type, e.g., a pneumatic actuator or a linear pneumatic actuator. The first actuator 236 may be configured to move the first movable member 231 between its first and second positions. The container 196 may optionally include a limiter 237 of any suitable type for limiting the distance that the end surface 232 of the first movable member 231 may travel within the cavity receiving portion 197a. For example, the connector block 233 may engage an end or limiting surface, such as the limiter 237, at the top opening 201 of the cavity receiving portion 197a, thereby limiting the movement of the first movable member 231 relative to the funnel 198. The first movable member 231 can optionally slide along an inner surface of the cavity receiving portion 197a when moving between the first and second positions. The end face 232 can be close to, if not engaged with, the bottom opening 202 of the funnel 198 when in its second position. The end face 232 of the first movable member 231 can optionally extend at least partially through the top opening 217 of the container center 206 into the cavity center 197b when in its second position.

[0065] The first movable member 231 may be referred to as a compression or compaction component or member, or a plunger. Movement of the first movable member 231 from its first position to its second position causes the pharmaceutical powder disposed in the cavity receiving portion 197a to move downward within the funnel 198 toward the bottom opening 202 and into the cavity center portion 197b of the first end portion 206a of the container center 206. An end surface 232 of the first movable member 231 may optionally have a size and cross-sectional shape that matches the size and cross-sectional shape of the bottom opening 202 of the funnel 198 and the top opening 217 of the first end portion 206a of the container center 206, such that the pharmaceutical powder in the cavity receiving portion 197a is pushed by the first movable member 231 into the cavity center portion 197b.

[0066] The machine 191 may optionally be slidably or movably supported by the support structure 192, for example by the container 196, and may include a second movable member 241 that is movable within the cavity center 197b to vary the size and volume of the cavity center 197b (see FIGS. 18 and 20). In this regard, for example, the second movable member 241 may be slidably or movable between a first or retracted position, for example as shown in FIG. 20, in which the size of the cavity center 197b is relatively large, and a second or extended or compacted position, not shown, in which the size of the cavity center 197b is relatively small with a reduced volume. The second movable member 241, including any multiple components that form the second movable member 241, may be made from any suitable material, such as metal or plastic.

[0067] The second movable member 241 optionally includes a first end portion 241a and a second end portion 241b having an end surface 242. The first end portion 241a can be joined in any suitable manner to a second actuator 243 (e.g., a motor) of any suitable type, e.g., a pneumatic actuator or a linear pneumatic actuator. The second actuator 243 can be configured to move the second movable member 241 between its first and second positions. The container 196 can optionally include a limiter, not shown, of any suitable type, for limiting the distance that the end surface 242 of the second movable member 241 can travel within the cavity center 197b. The end surface 242 can optionally be close when not engaged with the opening of the slot 221 of the end block 223 when in its second position. The end face 242 of the second movable member 241 may optionally extend at least partially through the openings of the slot 221 and notch 76 to a position extending tangentially to a side of the internal passage 74 of the elongated member 71.

[0068] The second movable member 241 may be referred to as a compression or compaction component or member, or a plunger. Movement of the second movable member 241 from its first position to its second position moves the pharmaceutical powder disposed in the cavity center 197b down the cavity center 197b from the first end portion 206a of the container center 206 to the second end portion 206b of the container center toward and into the cavity end portion 197c. The end face 242 of the second movable member 241 may optionally have a size and cross-sectional shape that matches the size and cross-sectional shape of the cavity center 197b, such that the pharmaceutical powder in the cavity center 197b cannot easily pass between the end face 242 and the wall of the container center 206 that forms the cavity center 197b slidably engaged by the end face 242.

[0069] End surface 242 may be of any suitable configuration, for example, planar or arcuate. End surface 242 may optionally be planar and perpendicular to the planar side of second movable member 241. End surface 242 may optionally be arcuate, for example, concave. Such concave end surface 242 may optionally have a radius approximately equal to the radius of interior passageway 74 of elongate member 71.

[0070] Machine 191 may optionally include a mold and corresponding recesses (not shown in FIGS. 17-20, respectively) for forming the microtablets of the present technology, similar to mold 111 and recess 112 of machine 31 shown in FIGS. 8 and 9. Mold 111 may be referred to as a forming section, and recess 112 may be referred to as a forming area. Machine 191 may optionally include a mold carrier of any suitable size and shape, e.g., an elongated plate such as slide 213 supported by support structure 192. In such a configuration, slide 213 may include a first end portion 213a and an opposing second end portion 213b, and may include an upper surface 251 and a lower surface 252. Mold 111 may be formed integrally with slide 213, e.g., from the same material as slide 213, or may be formed from a different material than slide 213 and secured within slide 213. The mold 111 can optionally extend between an upper surface 251 and a lower surface 252 of the slide 213, and the recess 112 can have a first opening in the upper surface 251 and a second opening in the lower surface 252.

[0071] The slide 213 may be movable or slidable relative to the track 214 between a first position, e.g., as shown in Figs. 17 and 18, and a second position, not shown, extending further along the y-axis. The first end portion 213a may be joined in any suitable manner to any suitable type of actuator or motor, e.g., a pneumatic actuator or a linear pneumatic actuator, such as the slide actuator 253. The slide actuator 253 may be configured to move the slide 213 between its first and second positions. When the slide 213 is in its first position, which may be referred to as a receiving position, one end of the recess 112 of the mold 111 is optionally aligned with an open end of the interior passage 74 of the container 196, and the other end of the recess 112 is sealed, e.g., by the base block 216. When the slide 213 is in its second position, which may be referred to as a discharge position, the recess 112 of the mold 111 is optionally accessible at both ends of the recess, e.g., on both sides of the slide 113.

[0072] Machine 191 may optionally include a third movable component or member of any suitable type, such as third movable member 141 as discussed and illustrated above with respect to machine 31. As mentioned above, third movable member 141 may include a first end portion 141a and an opposite second end portion 141b having an end face 142. End face 142 may be movable within cavity 197, e.g., cavity end portion 197c, to change the size and optionally the shape of a portion of cavity 197, e.g., cavity end portion 197c. In this regard, for example, third movable member 141 may be slidable or movable between a first or retracted position, e.g., as shown in Figures 17 and 18, in which end face 142 is outside cavity end portion 197c, and a second or compacted position, not shown, in which end face 142 extends at least into cavity end portion 197c. The third movable member 141 may optionally be disposed within a first end of the internal passageway 74 of the elongate member 71 when in its first position. The third movable member may optionally be further disposed within the internal passageway 74, e.g., near a second end of the internal passageway 74 or within the recess 112, when in its second position.

[0073] The third movable member 141, which may be referred to as a compression or compaction component or member, plunger, compactor, reciprocating member, repeating member, component, or compactor, or a reciprocating cylindrical member, is optionally held in a predetermined position on or within the vessel 196 or by the support structure 192 by any suitable means. In this regard, for example, the first end portion 141a of the third movable member may be joined in any suitable manner to a third actuator 261 (e.g., a motor) of any suitable type, such as a pneumatic actuator or a linear pneumatic actuator. The third actuator 261 may be configured to move the third movable member 141, including its end surface 142, between its first and second positions. The third actuator 261 may move or reciprocate the third movable member 141 between its first and second positions at any suitable speed, rate, or frequency. The actuator can optionally control the pressure or force exerted by the end surface 142 of the third movable member 141 on the powder or other material forming the microtablets of the present technology, including the duration of such pressure or force.

[0074] Machine 191 may optionally include an ejector 266 for moving a compacted or cylindrical mass formed by machine 191 from recess 112 of mold 111, for example, when slide 213 is in its second position. Ejector 266 may be supported in any suitable manner by support structure 192, for example, by vertical plate 193. Ejector 266 may be of any suitable type and may optionally include pins 157 having end faces 158, each as discussed and shown above for machine 31. When slide 213 is in the second position, the first opening of recess 112 is aligned with pin 157 and the second opening of recess 112 is free from any lid surface. The pin 157 can be movable between a first or retracted position, in which the end face 158 is outside the recess 112, and a second or extended position, in which the end face 158 is disposed at least partially through, completely through, or through the recess 112 to urge the compacted mass or cylinder formed by the machine 191 out of the recess. The ejector 266 can include a suitable ejector actuator 267 (e.g., a motor) for moving the pin 157 between its first and second positions. The ejector actuator 267 can move the pin 157 from its first position to its second position at any suitable speed. The actuator can optionally control the pressure or force exerted by the end face 158 of the pin 157 on the powder or other material forming the microtablets of the present technology, including the duration of such pressure or force.

[0075] The machine 191 may optionally include a collector 271 for receiving the micro-tablets pushed out of the mold recesses 112 by the ejector 266. The collector 271 may be of any suitable type and may optionally include a receiver such as a tray 272 having a plurality of compartments 273, each of which may hold one or more micro-tablets formed by the machine 191. The compartments 273 may optionally be spaced apart, for example, along a linear or arcuate length of the tray 272, or in a grid on the tray 272. The tray may optionally be movable, for example manually or by any suitable actuator or motor, to sequentially align the compartments 273 of the tray 272 near the exit opening of the recesses 112 for receiving one or more micro-tablets pushed out or ejected from the recesses by the ejector 266.

[0076] Each of the actuators of the machine 191, for example, the first actuator 236, the second actuator 243, the slide actuator 253, the third actuator 261, and the ejector actuator 267, may each be coupled to the controller 33, or any other suitable controller of the present technology, by a respective one or more lines 276. Such lines may optionally be pneumatic lines or electrical wires to enable a controller of the present technology to control such actuators.

[0077] The device, apparatus, or machine of the present technology may have other configurations as well. The machine, such as the apparatus, device, or machine 291 shown in Figures 21-25, may optionally be included in a system 32, which may additionally include a controller 33 or any other suitable controller. The machine 291, which may be referred to as a microtabletting machine, may optionally include a support structure 292 having a base, which may include a vertical plate 293 (see Figure 21). The support structure 292, including the vertical plate 293, may be formed from any suitable material, such as metal or plastic.

[0078] The machine 291 includes a container 296 in which a cavity 297 is provided for receiving pharmaceutical powder or other drug from which the microtablets of the present technology are formed. A portion or the entirety of the cavity 297 can optionally be referred to as a filling area. The container 296, including a portion thereof, can be formed from any suitable material, such as metal or plastic. The container 296 can be of any suitable type, can optionally be funnel-shaped, and can optionally include a first or top portion, referred to herein as a funnel 298. The funnel 298 can be formed from first and second sides, side components, or side portions 299 that can be joined by any suitable means. The upright or vertical funnel 298, shown extending generally along the z-axis in FIG. 21, has an upper portion 298a and a lower portion 298b that decrease in size and cross-sectional area or taper or narrow inwardly from the upper portion to the lower portion. The cavity receiver 297a is formed by a funnel having an upper opening 301 at the top of the upper portion 298a for providing the pharmaceutical powder to the cavity receiver 297a, and a smaller lower opening 302 at the bottom of the funnel's lower portion 298b for allowing the pharmaceutical powder to exit the cavity receiver 297a. Similar to the funnel 288, the cavity receiver 297a decreases in size and cross-sectional area, or tapers or narrows inwardly, from the upper opening 301 to the lower opening 302. The funnel 288 and cavity receiver 297a may extend along any suitable arc and through any suitable angle from the horizontal upper opening 301 to the angled lower opening 302 (see FIGS. 21-23).

[0079] The container 296 optionally includes a container center 306 joined to a bottom portion 298b of the funnel 298. The container center 306 may have a first end portion 306a and a second end portion 306b. The container center 306 may optionally be elongated and extend along any suitable arc through any suitable angle from the first end portion 306a to the second end portion 306b. For example, the container center 306 may extend through such an arc in the yz plane (see FIG. 21 ). The container center 306 has an elongated chamber between the first end portion 306a and the second end portion 306b that may be referred to as the cavity center 297b of the cavity 297, extending through the arc of the container center 306. The cavity center 297b is formed from opposing inner surfaces 307, 308 of respective sidewalls 311, 312 of the container center 306 that extend generally parallel to one another (see FIG. 24). The cavity center 297b can optionally have a rectangular cross-sectional area when viewed in cross section at an angle perpendicular to the arc of the cavity center 297b. The cavity center 297b can optionally have a constant internal cross-sectional shape and area along its arcuate length. The container center 306 is provided with an upper opening 317, for example at the first end portion 306a, that communicates with the lower opening 302 of the funnel 298 to allow material in the funnel-formed cavity receiver 297a to enter the cavity center 297b.

[0080] The cavity 297 may optionally include a cavity end portion 297c at an end of the cavity center 297b, which may optionally be at least partially formed from the elongated member 71. The elongated member 71 may have some or all of the configurations, materials, and other features discussed above with respect to the machine 31. The elongated member 71 may optionally be supported by a support structure 292 in any suitable manner, for example, in a slot 221 extending vertically along a surface 222 of an end block 223 joined to the second end portion 306b of the container center 306 by any suitable means (see FIG. 25). The slot 221, surface 222, and end block 223 may each have some or all of the configurations, materials, and other features discussed above with respect to the machine 191. The notch 76 of the elongated member 71 may optionally be aligned with the end of the cavity center 297b formed in the second end portion 306b of the container center 306. The internal passage 74 may optionally have a cross-sectional dimension or diameter that is approximately equal to the width of the cavity center 297b. The notch 76 and the internal passage 74 may be referred to as the cavity end portion 297c.

[0081] Part or all of the container 296 may optionally be referred to as a variable funnel in that the shape of the cavity 297 may change during use, and similarly, the volume of the cavity 297 may change during use. For example, the volume of the passageway along which the pharmaceutical composition or powder travels from the entrance of the cavity 297, i.e., the entrance in the cavity receiving portion 297a, to the interior passageway 74 in the elongated member 71 at the cavity end portion 297c, decreases in volume along the path of such travel. Part or all of the cavity 297 may be referred to as a volume reduction region. Part or all of the container 296 may be referred to as a volume reduction chamber, a compaction chamber, a powder compression chamber, or any combination of the foregoing.

[0082] The machine 291 may optionally include at least one movable component or member that may be slidably or movably supported by the support structure 392, for example by the container 296, and may optionally include a first movable member 331 that may be movable within the cavity receiving portion 297a to vary the size and volume of the cavity receiving portion 297a. In this regard, for example, the first movable member 331 may be slidably or movable between a first or retracted position, for example as shown in Figures 21-22 and 24, in which the size of the cavity receiving portion 297a is relatively large, and a second or extended or compacted position in which the first movable member 331 at least partially extends into the cavity receiving portion 297a, in which the size of the cavity receiving portion 297a is relatively small with a reduced volume. The first movable member 331 may optionally and additionally be movable within the cavity center 297b to vary the size and volume of the cavity center 297b. In this regard, for example, the first movable member 331 may be slidable or movable between a third position or retracted position outside the cavity center 297b, where the size of the cavity center 297b is relatively large, and a fourth position or extended position or compacted position, where the size of the cavity center 297b is reduced in volume and relatively small, as shown, for example, in Figures 23 and 25 .

[0083] The first movable member 331 can be any suitable shape and size, and can optionally have a size and shape corresponding to the cavity center 297b, the cavity receiving portion 297a, or both. For example, the first movable member 331 can optionally have an arc shape in the yz plane corresponding to the arc of the cavity center 297b, the arc of the cavity receiving portion 297a, or both. The first movable member 331 can optionally be planar in the xz plane. The first movable member 331, including any components thereof, can be made of any suitable material, such as metal or plastic.

[0084] The first movable member 331 optionally includes a first end portion 331a and an opposite second end portion 331b having an end surface 332. The first end portion 331a may be joined in any suitable manner to an actuator 336 (e.g., a motor) of any suitable type, e.g., a pneumatic actuator or a rotary pneumatic actuator. The actuator 336, which may be supported, for example, by a support structure 292 fixed to a vertical plate 293, may be configured to move the first movable member 331 between its first and second positions and between its third and fourth positions. The container 296 may optionally include one or more limiters, not shown, of any suitable type, for limiting the distance the end surface 332 of the first movable member may travel within the cavity receiving portion 297a, the cavity center 297b, or both.

[0085] The first movable member 331 may be referred to as a compression or compaction component or member, or a plunger. Movement of the first movable member 331 from its first position to its second position causes the pharmaceutical powder disposed in the cavity receiving portion 297a to move downward within the funnel 298 toward the bottom opening 302 and into the cavity center 297b of the first end portion 306a of the container core 306. An end face 332 of the first movable member 331 may optionally have a size and cross-sectional shape that matches the size and cross-sectional shape of the bottom opening 302 of the funnel 298 and the inlet or top opening 317 of the first end portion 306a of the container core 306, such that the pharmaceutical powder in the cavity receiving portion 297a is pushed by the first movable member 331 into the cavity center 297b.

[0086] Movement of the first movable member 331 from its third position to its fourth position causes the pharmaceutical powder disposed in the cavity center 297b to move down the cavity center 297b from the first end portion 306a of the container center 306 to the second end portion 306b of the container center 306 toward and into the cavity end portion 297c. An end surface 332 of the first movable member 331 can optionally has a size and cross-sectional shape that matches the size and cross-sectional shape of the cavity center 297b such that the pharmaceutical powder in the cavity center 297b cannot easily pass between the end surface 332 and the wall of the container center 306 that forms the cavity center 297b that is slidably engaged by the end surface 332.

[0087] The end surface 332 can be of any suitable configuration, for example, planar or arcuate. The end surface 332 can optionally be planar and perpendicular to the planar sides of the first movable member 331, and can be planar and perpendicular to the arc of the first movable member. The end surface 332 can optionally be arcuate, for example, concave between the planar sides of the first movable member 331. Such a concave end surface 332 can optionally have a radius approximately equal to the radius of the interior passageway 74 of the elongate member 71.

[0088] Machine 291 may optionally include a mold 111 having recesses 112 for forming the microtablets of the present technology. Mold 111 may be referred to as a forming section and recesses 112 may be referred to as a forming area. Mold 111 shown in FIG. 21 and recesses 112 not shown with respect to machine 291 may each optionally be as discussed and shown above with respect to machine 31. Machine 291 may optionally include a mold carrier supported by support structure 292. Mold carrier may be any suitable size and shape, e.g., an elongated plate such as slide 213 discussed and shown above with respect to machine 191. Slide 213 may be movable or slidable relative to track 214 between a first position, e.g., as shown in FIGS. 17 and 18 with respect to machine 191, and a second position extending further along the y-axis, e.g., as shown in FIGS. 21-23 with respect to machine 291. First end portion 213a may be joined in any suitable manner to any suitable type of actuator or motor, e.g., slide actuator 253, which may be configured to move slide 213 between its first and second positions. When slide 213 is in its first position, which may be referred to as a receiving position, one end of recess 112 in mold 111 is optionally aligned with an open end of interior passage 74 of container 196, and the other end of recess 112 is sealed, e.g., by base block 216. When slide 213 is in its second position, which may be referred to as a ejection position, recess 112 in mold 111 is optionally accessible at both ends of the recess, e.g., on both sides of slide 213.

[0089] Machine 291 may optionally include additional movable components or members of any suitable type, e.g., third movable member 141 as discussed and illustrated above with respect to machines 31 and 191. Third movable member 141, including its end surface 142, may optionally be movable and operable in the manner discussed above. Third movable member 141 may be referred to as a compression or compaction component or member, plunger, compactor, reciprocating member, reciprocating motion member, component, or compactor, or a reciprocating cylindrical member. A first end portion 141a of the third movable member may be joined in any suitable manner to a third actuator or motor of any suitable type, e.g., third actuator 261, which may optionally be movable and operable in the manner discussed above.

[0090] Machine 291 may optionally include an ejector 266, which may optionally include a pin 157 having an end surface 158 and an ejector actuator 267, each as discussed and shown above with respect to machine 191. Ejector 266 may optionally be movable and operable in the manner discussed above.

[0091] Machine 291 may optionally include a collector 271 for receiving micro-tablets pushed out of recesses 112 by ejector 266, as discussed above with respect to machine 191. Collector 271 may optionally be movable and operable in the manner discussed above.

[0092] Each of the actuators of machine 291, for example actuator 336, slide actuator 253, third actuator 261, and ejector actuator 267, may be respectively coupled by one or more lines (not shown) to controller 33 or any other suitable controller of the present technology (not shown). Such lines may optionally be pneumatic lines or electrical wires to enable a controller of the present technology to control such actuators.

[0093] A method is provided for producing a compressed mass, which may be a microtablet of a pharmaceutical composition or drug. The compressed mass may be referred to as a cylindrical mass. The microtablet may be for ingestion or other consumption by a mammal, e.g., a human. The pharmaceutical composition or drug for forming the compressed mass may optionally be in the form of a pharmaceutical powder.

[0094] The method may include compressing, compacting, or pressing the powder to form a compressed mass of a certain density. In this regard, for example, an amount of pharmaceutical powder sufficient to form at least a single compressed mass may optionally be disposed or placed or provided within a cavity or chamber, for compression or otherwise, such as the filling area or cavity 47 of container 46, cavity 197 of container 196, or filling area or cavity 297 of container 296. Other amounts, for example, an amount of pharmaceutical powder at least sufficient to form multiple compressed masses or microtablets, may optionally be placed within cavity 297.

[0095] Compressing can optionally include compressing, compacting, or pushing the pharmaceutical powder in at least one direction, e.g., a first direction, or in multiple directions, e.g., including a first direction and a second direction. The first direction and the second direction can optionally be perpendicular to each other or at any other angle relative to each other. The compressed pharmaceutical powder can optionally be referred to as a compacted mass, e.g., a compacted mass of a certain density.

[0096] Compressing can optionally include compressing, compacting, or pushing the powder in at least one direction using at least one movable member, e.g., at least one movable compression or compacting member. Compressing can optionally include compressing, compacting, or pushing the powder in a first direction to form a collected mass of powder, and compressing or compacting the collected mass of powder in a second direction, e.g., in container 46. Compressing, compacting, or pushing the powder in the second direction can occur after, simultaneously with, or overlapping with compressing, compacting, or pushing the powder in the first direction.

[0097] Compressing can optionally include forcing the powder into a recess, mold, or other forming area to form microtablets. The powder can be compressed, compacted, or packed into the forming area to increase density and reduce the volume of the powder. The formed microtablets can be pushed, ejected, or otherwise removed from the forming area.

[0098] With respect to machine 31, compressing, compacting, or pushing can include compressing the powder by first movable member 81 in a first direction, e.g., along the y-axis identified in FIG. 3, within cavity 47, e.g., cavity receiver 47a. For example, first movable member 81 can be moved from a first position to a second position within cavity 47 such that end face 82 of first movable member 81 urges, and thus compresses, compacts, or otherwise gathers or guides, the pharmaceutical powder against inner end face 62 to form a collected mass of powder within cavity receiver 47a. The directing, compressing, or compacting by first movable member 81 can only act to collect the powder in a particular area of ​​cavity 47, or, optionally, to increase the density of the pharmaceutical powder within cavity 47, i.e., to have a first density. Compressing can optionally include compressing the powder by the second movable member 91 within the reduced cavity receiving portion 47a in a second direction, for example along the z-axis identified in FIG. 3. For example, the second movable member 91 can be moved from a first position to a second position within the cavity receiving portion 47a such that an end face 92 of the second movable member 91 urges, and thus compresses, compacts, or otherwise gathers or directs, the pharmaceutical powder within the cavity receiving portion 47a toward at least the cavity center portion 47b, and optionally toward the cavity center portion 47b and the cavity lower portion 47c (see FIG. 13). Compressing or compacting by the second movable member 91 can optionally serve to further increase the density of the pharmaceutical powder within the cavity 47, i.e., to have a second density that is higher than the first density. The movement of the second movable member 91 in the second direction can optionally be, and is shown in the figures as being, orthogonal to the movement of the first movable member 81 in the first direction. A compacted mass formed by at least one movable compression or compaction member, e.g., the first movable member 81, the second movable member 91, or both, can be referred to as a cylindrical mass or a compact cylindrical mass.For example, the compacted mass formed by the second movable member 91 in the cavity center portion 47b, or in the cavity center portion 47b and the cavity lower portion 47c, can be referred to as a cylindrical mass or a compact cylindrical mass extending along a longitudinal axis, for example, the longitudinal axis of the cavity center portion 47b or the cavity lower portion 47c.

[0099] In various embodiments, the method of the present technology can optionally further include compressing or compacting the compressed mass to increase the density of the compressed mass. For example, the compressed mass may be pushed from the cavity 47 into the recess 112 for further compression or compaction. Such compressing or compacting can optionally include repeatedly compacting the compressed mass. The compacting can optionally include repeatedly compacting the compressed mass, e.g., a compressed cylindrical mass, along a longitudinal axis of the mass. The compacting can optionally include repeatedly compacting the compressed mass in additional directions orthogonal to the first and second compression directions of the compacting. Further compacting the compressed mass can occur after, simultaneously with, or overlapping with compressing or compacting the powder in a first direction, compressing or compacting the powder in a second direction, or both.

[0100] Compacting can optionally include frequently or repeatedly compacting the compressed mass with a third movable member, which can be referred to as a compacting member, a reciprocating compacting member, or a reciprocating motion member. The third movable member can optionally be a third movable member 141, which can be referred to as a compacting member, a reciprocating member, a reciprocating compacting member, or a reciprocating motion member. The third movable member 141 can move from its first position to its second position in a third direction, for example along the x-axis identified in FIG. 3, along a longitudinal axis, for example along the longitudinal axis of the interior passage 74 of the elongated member 71 or the longitudinal axis of the recess 112. The movement of the third movable member 141 from its first position to its second position can optionally cause the end surface 142 of the third movable member 141 to push, place, or push out the packed pharmaceutical powder in the lower cavity portion 47c, e.g., in the internal passageway 74 of the elongated member 71, into the recess 112 of the mold 111, repeatedly compressing, compacting, or packing the powder in the recess 112. Such repeated movement, compacting, or packing of the compacted mass can optionally be with the first movable member 81 and the second movable member 91, e.g., with the end surface 82 of the first movable member and the end surface 92 of the second movable member. The compressing or compacting by the third movable member 141 can optionally serve to further increase the density of the pharmaceutical powder in the cavity 47, i.e., to have a third density higher than the second density. With each successive reciprocating motion of the movable member 141, the density of the powder gradually increases, creating a compacted solid mass of final density and shape to form a microtablet according to the present technology. The third direction of movement of the third movable member 141 can optionally be orthogonal to one or both of the direction of movement of the first movable member 81 and the direction of movement of the second movable member 91.

[0101] The third movable member 141 can optionally compress, compact, or pack some or all of the pharmaceutical powder in the cavity lower portion 47c, e.g., in the internal passage 74, into a recess 112 of the mold 111 supported by the slide 113. In this regard, for example, the second end of the recess 112 abuts the block 117 to seal the second end of the recess while the pharmaceutical powder is being packed, pushed, placed, disposed, or received into the recess by the third movable member 141. Compacting can optionally include pushing or placing the pharmaceutical powder in the cavity lower portion 47c into the recess 112 and then compacting or compressing the powder in the recess, e.g., repeatedly compressing or compacting the powder in the recess. The recess 112 can optionally be a cylindrical recess. The slide 113 can be held in its first position while it is being filled with pharmaceutical powder by engagement of the slide's first magnet 121 with the third magnet 123 of the first stopper 126, as well as by a locking mechanism 131.

[0102] The third movable member 141 can optionally reciprocate, for example, under the control of the controller 33 or any other controller of the present technology, to repeatedly or repeatedly compact or compress the pharmaceutical powder in the recess 112, and optionally in the lower cavity portion 47c or the internal passage 74, along the longitudinal axis of the recess 112, the internal passage 74, and the cylindrical mass. The controller 33 can include features for controlling various parameters related to the action and movement of the third movable member 141. For example, suitable knobs, levers, buttons, or other manually actuable components can be provided for controlling the pressure exerted by the third movable member 141 on the compacted mass, the time the third movable member 141 reciprocates, how quickly the third movable member reciprocates, or any combination of the foregoing. In this regard, the controller 33 may optionally include a knob 170 for controlling the amount of pressure exerted by the third movable member 141 on the compacted mass, a gauge 171 indicating such pressure, a first timer 172 indicating the total time that the third movable member 141 compresses the pharmaceutical powder, and a second timer 173 indicating how quickly, e.g., the frequency, the third movable member 141 reciprocates in and out of the recess 112. The pressure exerted by the third movable member 141 on the compacted mass may be any suitable amount or range, and may optionally be from 0 to 552 kPa (80 PSI).

[0103] Compressing the pharmaceutical powder in the recesses 112 can optionally serve to form mini-tablets having a perimeter that conforms to the inner surface of the recesses 112. Once the desired amount of pharmaceutical powder has been loaded into the recesses 112 of the mold 111, the locking mechanism 131 can be unlocked to allow movement of the slide 113 in the track 116 from its first position to its second position. The slide 113 can be held in its second position by engagement of the second magnet 122 at the second end of the slide 113 with the fourth magnet 127 of the second stop 128, as well as by engagement or activation of the locking mechanism 131. When the slide 113 is in its second position, the former or mold 111 can optionally be moved or extended away from the remainder of the machine 31, with the recesses 112 aligning or registering with the pins 157 of the ejector 156 (see FIG. 15 ). The ejector 156 can then be optionally operated, for example under the control of the controller 33 or any other controller of the present technology, to move the ejector pin 157 from its first position to its second position. Such movement of the pin 157 causes an end face 158 of the pin to engage the compressed mass or microtablets in the recess 112, for example at a first end of the recess at the first end of the former or die 111, and urge or push the compressed mass or microtablets out of the recess, for example at an opposite second end of the recess at the second end of the former or die. The compressed or shaped mass or microtablets can be collected at the second end of the former or die 111 by any suitable means.

[0104] With respect to the machine 191, compressing, compacting, or pushing can include compressing the powder in the cavity 197, e.g., the cavity receiver 197a, in a first direction, e.g., along the z-axis identified in FIG. 17, by the first movable member 231. For example, the first movable member 231 can be moved from its first position to its second position in the cavity 197, e.g., by a first actuator 236 under the control of the controller 33, such that the end face 232 of the first movable member 231 urges the pharmaceutical powder in the cavity receiver 197a downward through the lower opening 202 of the cavity receiver 197a and the upper opening 217 of the cavity center 197b to the first end portion 206a of the container center 206, thus compressing or compacting. Compressing can optionally include compressing the pharmaceutical powder in the first end portion 206a of the container center 206. The compressing or compacting by first movable member 231 may optionally serve to increase the density of the medicinal powder within cavity 197 .

[0105] Compressing can optionally include compressing the powder by the second movable member 241 in the cavity center 197b in a second direction, for example along the y-axis identified in FIG. 17. For example, the second movable member 241 can be moved from its first position to a second position in the cavity center 197b, for example by a second actuator 243 under the control of the controller 33, such that an end face 242 of the second movable member 241 urges the pharmaceutical powder in the cavity center 197b to move, and thus optionally compress or compact, the cavity end portion 197c. The compressing or compacting by the second movable member 241 can optionally serve to further increase the density of the pharmaceutical powder in the cavity 197. The movement of the second movable member 241 in the second direction can optionally be, and is shown in the figures as being, orthogonal to the movement of the first movable member 231 in the first direction. A compacted mass formed by at least one movable compression or compaction member, e.g., first movable member 231, second movable member 241, or both, may be referred to as a cylindrical mass or compact cylindrical mass. For example, the compacted mass formed by second movable member 241 in cavity end portion 197c may be referred to as a cylindrical mass or compact cylindrical mass extending along a longitudinal axis, e.g., the longitudinal axis of cavity end portion 197c.

[0106] The method of the present technology may optionally further include compressing or compacting the compressed mass to increase the density of the compressed mass. For example, the compressed mass may be pushed from the cavity 197 into the recess 112 in the slide 213 for further compression or compaction. Such compressing or compacting may optionally include repeatedly compacting the compressed mass. The compacting may optionally include repeatedly compacting the compressed mass, e.g., a compressed cylindrical mass, along a longitudinal axis of the mass. The compacting may optionally include repeatedly compacting the compressed mass in additional directions orthogonal to the first and second compression directions of the compacting. Further compacting the compressed mass may occur after, simultaneously with, or overlapping with compressing or compacting the powder in a first direction, compressing or compacting the powder in a second direction, or both.

[0107] Compacting can include frequently or repeatedly compacting the compressed mass with a third movable member, which can optionally be referred to as a compacting member, a reciprocating compacting member, or a reciprocating motion member. The third movable member can optionally be the third movable member 141 discussed above, which can optionally be referred to as a compacting member, a reciprocating member, a reciprocating compacting member, or a reciprocating motion member. The third movable member 141 can be moved from its first position to its second position in a third direction, for example along the z-axis identified in FIG. 17, along a longitudinal axis, for example the longitudinal axis of the interior passage 74 of the elongated member 71 or the longitudinal axis of the recess 112. The third movable member 141 can be movable by a third actuator 261 under the control of the controller 33. Movement of the third movable member from its first position to its second position may optionally cause end surface 142 of third movable member 141 to push, place, or push out the packed pharmaceutical powder within cavity end portion 197c, e.g., within internal passageway 74 of elongated member 71, into recess 112 of mold 111 within slide 213, repeatedly compressing, compacting, or packing the powder within recess 112. The compressing or compacting by third movable member 141 may optionally serve to further increase the density of the pharmaceutical powder within cavity 197. A third direction of movement of third movable member 141 may optionally be orthogonal to one or both of the directions of movement of first movable member 231 and second movable member 241. For example, the direction of movement of the third movable member 141 may be perpendicular to the direction of movement of the second movable member 241 but generally parallel to the direction of movement of the first movable member 231 .

[0108] The third movable member 141 can optionally compress, compact, or pack some or all of the pharmaceutical powder in the cavity end portion 197c, e.g., in the internal passage 74, into the recess 112 of the mold 111 supported by the slide 213. In this regard, for example, the second end of the recess 112 can abut the base block 216 to seal the second end of the recess while the pharmaceutical powder is being packed, pushed, placed, disposed, or received into the recess by the third movable member 141. Compacting can optionally include pushing or placing the pharmaceutical powder in the cavity end portion 197c into the recess 112 and then compacting or compressing the powder in the recess, e.g., by repeatedly compressing or compacting the powder in the recess, whereby with each successive reciprocating motion of the movable member 141, the density of the powder gradually increases to create a compacted solid mass of final density and shape to form a microtablet according to the present technology. The recess 112 may optionally be a cylindrical recess. The slide 213 may optionally be held in its first position by a second actuator 243 under the control of the controller 33 while it is being filled with the pharmaceutical powder.

[0109] The third movable member 141 may optionally reciprocate, for example under the control of the controller 33 or any other controller of the present technology, to repeatedly or repeatedly compact or compress the pharmaceutical powder within the recess 112, and optionally within the cavity end portion 197c or the internal passage 74, along the longitudinal axis of the recess 112, the internal passage 74, and the cylindrical mass. As mentioned above, the controller 33 may include features for controlling various parameters related to the action and movement of the third movable member 141, and may optionally operate in the manner discussed above.

[0110] Compressing the pharmaceutical powder in the recesses 112 can optionally serve to form mini-tablets having a perimeter that conforms to the inner surface of the recesses 112. Once the desired amount of pharmaceutical powder has been loaded into the recesses 112 of the mold 111, the slide 213 is moved in the track 214 by the slide actuator 253 from its first position to its second position such that the second end portion 213b of the slide is aligned or aligned with the pin 157 of the ejector 266. When the slide 213 is moved to its second position, the former or mold 111 can optionally be moved or extended away from the remainder of the machine 191 to align the ejector 266 with the pin 157. The ejector 156 can then optionally be actuated, for example, by the ejector actuator 267 under the control of the controller 33, to move the ejector pin 157 from its first position to its second position. Such movement of the pin 157 causes the pin end face 158 to engage the compressed mass or microtablets in the recess 112, e.g., at a first end of the recess at the first end of the former or die 111, and urge or push the compressed mass or microtablets out of the recess, e.g., at an opposite second end of the recess at the second end of the former or die. The compressed or shaped mass or microtablets can be collected at the second end of the former or die by any suitable means, e.g., in a desired section 273 of a collector 271.

[0111] With respect to machine 291, compressing, compacting, or pushing can include compressing powder in cavity 297, e.g., cavity receiver 297a, in a first direction, e.g., in a rotational motion about an axis extending along the x-axis identified in FIG. 21, by first movable member 331. For example, first movable member 331 can be moved from its first position in cavity 297 to its second position, e.g., by rotary actuator 336 under the control of controller 33, such that end face 332 of first movable member 331 urges, and thus compresses, compacts, gathers, or otherwise directs, the pharmaceutical powder in cavity receiver 297a downwardly through sloped lower opening 302 of cavity receiver 297a and sloped upper opening 317 of cavity center 297b, toward first end portion 306a of container center 306. Compressing may optionally include compressing the pharmaceutical powder within the first end portion 306a of the container core 306. Compressing or compacting by the first movable member 331 optionally serves to increase the density of the pharmaceutical powder within the cavity 297 from a first density to a second density.

[0112] Compressing can optionally include compressing the powder by the first movable member 331 in the cavity center 297b in a first direction, e.g., in the same rotational motion in the yz plane, about an axis extending along the x-axis identified in FIG. 21. For example, the first movable member 331 can be moved from its third position to its fourth position in the cavity center 297b, e.g., by an actuator 336 under the control of the controller 33 (not shown in FIG. 21), such that the end face 332 of the first movable member 331 urges the pharmaceutical powder in the cavity center 297b to move, and thus optionally compress or compact, the cavity end portion 297c. Compressing or compacting by the first movable member 331 in the cavity center 297b can optionally serve to further increase the density of the pharmaceutical powder in the cavity 297. The direction of movement of the first movable member 331 in the cavity center 297b is the same direction of movement of the first movable member in the cavity receiving portion 297a. The compacted mass formed by at least one movable compression or compacting member, e.g., by the first movable member 331, can be referred to as a cylindrical mass or a compact cylindrical mass. For example, the compacted mass formed by the first movable member 331 in the cavity end portion 297c can be referred to as a cylindrical mass or a compact cylindrical mass extending along a longitudinal axis, e.g., the longitudinal axis of the cavity end portion 297c.

[0113] The method of the present technology can optionally further include compressing or compacting the compressed mass to increase the density of the compressed mass. For example, the compressed mass may be pushed from the cavity 297 into the recess 112 in the slide 213 for further compression or compaction. Such compressing or compacting can optionally include repeatedly compacting the compressed mass. The compacting can optionally include repeatedly compacting the compressed mass, e.g., the compressed cylindrical mass, along the longitudinal axis of the mass by repeatedly compressing or compacting the powder in the recess, whereby with each successive reciprocating movement of the movable member 141, the density of the powder gradually increases, creating a compacted solid mass of final density and shape to form a microtablet according to the present technology. The compacting can optionally include repeatedly compacting the compressed mass in additional directions perpendicular to the first compression direction of the compacting. Further compacting of the compressed mass can be performed after, simultaneously with, or overlapping with the compressing or compacting of the powder in the first direction.

[0114] Compacting may optionally include frequently or repeatedly compacting the compressed mass with an additional movable member, which may be referred to as a compacting member, a reciprocating compacting member, or a reciprocating motion member. The additional movable member may optionally be the third movable member 141 discussed above, which may be referred to as a compacting member, a reciprocating member, a reciprocating compacting member, or a reciprocating motion member. For example, the third movable member 141, movable by a third actuator 261 under the control of the controller 33, may optionally be movable and operable in the same manner as discussed above with respect to the machine 191. For example, movement of the third movable member from its first position to its second position can optionally cause end surface 142 of third movable member 141 to push, place, or push medicinal powder packed within cavity end portion 297c, e.g., within internal passageway 74 of elongated member 71, into recess 112 of mold 111 in slide 213, as described above, repeatedly compressing, compacting, or packing the powder within recess 112. The direction of movement of third movable member 141 can optionally be perpendicular to the direction of movement of first movable member 331.

[0115] The third movable member 141 can optionally compress, compact, or pack some or all of the pharmaceutical powder within the cavity end portion 297c, e.g., within the internal passageway 74, into the recess 112 of the mold 111 supported by the slide 213. Such actions and interactions of the third movable member 141, the recess 112, the mold 111, and the slide 213 can optionally be the same as those discussed above with respect to the machine 191.

[0116] The third movable member 141 may optionally reciprocate, for example, under the control of the controller 33 or any other controller of the present technology, to repeatedly or repeatedly compact or compress the pharmaceutical powder within the recess 112, and optionally within the cavity end portion 297c or the internal passage 74, along the longitudinal axis of the recess 112, the internal passage 74, and the cylindrical mass. As mentioned above, the controller 33 may include features for controlling various parameters related to the action and movement of the third movable member 141, and may optionally operate in the manner discussed above.

[0117] Compressing the pharmaceutical powder in the recesses 112 can optionally serve to form mini-tablets having a perimeter that conforms to the inner surface of the recesses 112. Once the desired amount of pharmaceutical powder has been loaded into the recesses 112 of the mold 111, the slide 213 is moved in the track 214 by the slide actuator 253 from its first position to its second position such that the second end portion 213b of the slide 213 aligns or aligns with the pin 157 of the ejector 266. When the slide 213 is moved to its second position, the former or mold 111 can optionally be moved or extended away from the remainder of the machine 291 to align the ejector 266 with the pin 157. The ejector 156 can then optionally be actuated, for example, by the ejector actuator 267 under the control of the controller 33, to move the ejector pin 157 from its first position to its second position. Such movement of the pin 157 causes the pin end face 158 to engage the compressed mass or microtablets in the recess 112, e.g., at a first end of the recess at the first end of the former or die 111, and urge or push the compressed mass or microtablets out of the recess, e.g., at an opposite second end of the recess at the second end of the former or die. The compressed or shaped mass or microtablets can be collected at the second end of the former or die by any suitable means, e.g., in a desired section 273 of a collector 271.

[0118] In various embodiments, the method of the present technology can include automating the actions of the first movable member of the present technology, the second movable member of the present technology, the third movable member of the present technology, or any combination of the above. The method of the present technology can optionally further include automating the placement of pharmaceutical powder into the filling region or cavity of the present technology. The placement of pharmaceutical powder into the filling region or cavity and the pushing of pharmaceutical powder from the filling region or cavity to the forming region of the present technology can optionally be automated and can optionally be a repetitive motion. The controller 33 or any other controller of the present technology can optionally be configured to engage in such a repetitive motion when the cavity contains a predetermined amount of pharmaceutical powder.

[0119] Microtablet embodiments of the present technology can be of any suitable size or volume. The microtablets can optionally have a volume of 1.3 to 1.5 cubic millimeters. The microtablets can optionally have a volume of about 3 cubic millimeters.

[0120] It should be appreciated that the apparatus and methods of the present technology can be configured to produce more than one microtablet in each cycle. For example, the compressed mass formed in one cycle of the methods and apparatus of the present technology can be sliced ​​or cut into more than one microtablet for ingestion or other consumption by a human or other mammal. For example, the length of the recess 112 can be dimensioned such that the compressed mass produced therein can be cut along its length to provide multiple microtablets.

[0121] The machine and method embodiments of the present technology avoid using large forces to create microtablet embodiments for delivery to humans or other mammals by oral, injection, or other methods known in the drug delivery art. Instead, the machine and method of the present technology advantageously use small, low, or minimal forces, which may include application in multiple directions, for example, sequentially to compress and compact pharmaceutical powders or other materials in stages to create microtablets. Such small, low, or minimal forces inhibit or reduce damage to pharmaceutical powders or other materials during the fabrication process, for example, by preventing bond scission in large drug molecules that may reduce or eliminate the biological activity and thus the effectiveness of such molecules, or alter the drug formulation. In use, such embodiments allow for the fabrication of microtablets comprising pharmaceuticals with minimal loss of pharmaceutical biological activity.

[0122] From the description herein, it will be understood that the present disclosure includes a number of embodiments, including, but not limited to, the following.

[0123] 1. 1. A machine for producing microtablets from pharmaceutical powders for human consumption, comprising: a support structure having a container for receiving the powder; a first movable member supported by the support structure for directing the powder in the container in a first direction; a second movable member supported by the support structure for compacting the powder in the container in a second direction to form a compact mass of the medicament; and Equipped machine.

[0124] 2. the compact mass being a compact cylindrical mass extending along a longitudinal axis; The machine, a third movable member supported by said support structure for continuously compacting said compact cylindrical mass along said longitudinal axis. Further comprising: 20. A method or apparatus according to any preceding or following embodiment.

[0125] 3. a mould having a recess in the form of said micro-tablet for receiving said compact cylindrical mass under the force of said third movable member; Further comprising: 20. A method or apparatus according to any preceding or following embodiment.

[0126] 4. a cylindrical pin movable from a first position outside the recess to a second position within the recess to eject the microtablet from the recess; Further comprising: 20. A method or apparatus according to any preceding or following embodiment.

[0127] 5. the first movable member having a surface for engaging the powder to guide the powder; the second movable member moves along the face of the first movable member between a first position and a second position to compact the powder. 20. A method or apparatus according to any preceding or following embodiment.

[0128] 6. the second movable member comprises a reciprocating member configured to continuously compact the powder in the second direction. 20. A method or apparatus according to any preceding or following embodiment.

[0129] 7. the second direction is perpendicular to the first direction; the longitudinal axis is perpendicular to one or more of the first direction and the second direction; 20. A method or apparatus according to any preceding or following embodiment.

[0130] 8. the container comprises a cavity; the surface of the first movable member is configured to direct the powder to a first location within the cavity; the second movable member compacts the powder at a second location within the cavity. 20. A method or apparatus according to any preceding or following embodiment.

[0131] 9. A third movable member comprising a reciprocating member. Further equipped with the reciprocating member is configured to continuously compact the powder at a third location within the cavity. 20. A method or apparatus according to any preceding or following embodiment.

[0132] 10. one or more actuators for automatically affecting the movement of one or more of the first movable member, the second movable member, and the third movable member; Further comprising: 20. A method or apparatus according to any preceding or following embodiment.

[0133] 11. a controller coupled to the one or more actuators Further equipped with The controller is configured to control one or more of a timing of actuation of the actuator and a force applied by the actuator for selective compaction of the micro-tablets. 20. A method or apparatus according to any preceding or following embodiment.

[0134] 12. 1. An apparatus for producing microtablets from pharmaceutical powders, comprising: a container having a cavity for receiving the powder; a first movable member configured to direct the powder within the container in a first direction and collect the powder at a first location within the cavity; a second movable member configured to compact the powder in the container in a second direction to form a solid microtablet having a compressed mass and shape; and Equipped Device.

[0135] 13. the compressed mass being a compact cylindrical mass extending along a longitudinal axis; The apparatus, a third movable member supported by said support structure for continuously compacting said compact cylindrical mass along said longitudinal axis. Further comprising: 20. A method or apparatus according to any preceding or following embodiment.

[0136] 14. a mould having a recess in the form of said micro-tablet for receiving said compact cylindrical mass under the force of said third movable member; Further comprising: 20. A method or apparatus according to any preceding or following embodiment.

[0137] 15. a cylindrical pin movable from a first position outside the recess to a second position within the recess to eject the microtablet from the recess; Further comprising: 20. A method or apparatus according to any preceding or following embodiment.

[0138] 16. the first movable member having a surface for engaging the powder to guide the powder; the second movable member moves along the face of the first movable member between a first position and a second position to compact the powder. 20. A method or apparatus according to any preceding or following embodiment.

[0139] 17. the second movable member comprises a reciprocating member configured to continuously compact the powder in the second direction. 20. A method or apparatus according to any preceding or following embodiment.

[0140] 18. the second direction is perpendicular to the first direction; the longitudinal axis is perpendicular to one or more of the first direction and the second direction; 20. A method or apparatus according to any preceding or following embodiment.

[0141] 19. A third movable member comprising a reciprocating member. Further equipped with the reciprocating member is configured to continuously compact the powder at a third location within the cavity. 20. A method or apparatus according to any preceding or following embodiment.

[0142] 20. one or more actuators for automatically affecting the movement of one or more of the first movable member, the second movable member, and the third movable member; Further comprising: 20. A method or apparatus according to any preceding or following embodiment.

[0143] twenty one. a controller coupled to the one or more actuators Further equipped with The controller is configured to control one or more of a timing of actuation of the actuator and a force applied by the actuator for selective compaction of the micro-tablets. 20. A method or apparatus according to any preceding or following embodiment.

[0144] twenty two. 1. A method for producing microtablets from a pharmaceutical powder for human consumption, comprising the steps of: inducing the powder to form a collected mass of the powder at a first density; repeatedly compacting the collected mass of powder to gradually increase the density of the collected mass of powder to form a compacted mass of a final density and shape. Includes method.

[0145] twenty three. The compressed mass is cylindrical in shape and extends along a longitudinal axis. 20. A method or apparatus according to any preceding or following embodiment.

[0146] twenty four. The iterative compacting comprises: repeatedly compacting said cylindrical mass along said longitudinal axis; Including, 20. A method or apparatus according to any preceding or following embodiment.

[0147] twenty five. The iterative compacting comprises: repeatedly compacting said cylindrical mass into a cylindrical die to form said minitablets. Including, 20. A method or apparatus according to any preceding or following embodiment.

[0148] 26. Inducing the powder compacting said powder in at least one direction to form a compressed mass of said first density. Including, 20. A method or apparatus according to any preceding or following embodiment.

[0149] 27. Inducing the powder compressing the powder in a first direction. Including, and compacting the powder in a second direction perpendicular to the first direction. 20. A method or apparatus according to any preceding or following embodiment.

[0150] 28. The iterative compacting comprises: repeatedly compacting the compressed mass in additional directions perpendicular to the first direction and the second direction. Including, 20. A method or apparatus according to any preceding or following embodiment.

[0151] 29. To induce, using a funnel to induce said powder to form said compacted mass. Including, 20. A method or apparatus according to any preceding or following embodiment.

[0152] 30. The compacting step comprises: compacting said powder in at least one direction using at least one movable compacting member. Including, 20. A method or apparatus according to any preceding or following embodiment.

[0153] 31. Inducing the powder directing the powder in a first direction with a first movable member and compressing the powder in a second direction with a second movable member to form a compact cylindrical mass of the powder extending along a longitudinal axis. Including, 20. A method or apparatus according to any preceding or following embodiment.

[0154] 32. The iterative compacting comprises: repeatedly compacting said compact cylindrical mass along said longitudinal axis with a reciprocating third compacting member. Including, 20. A method or apparatus according to any preceding or following embodiment.

[0155] 33. The pharmaceutical powder comprises a large drug molecule having at least one of a protein, a peptide, and an antibody. 20. A method or apparatus according to any preceding or following embodiment.

[0156] 34. the pharmaceutical powder comprises a biological activity; the biological activity of the pharmaceutical powder in the formed minitablets is at least 70% of the biological activity before compression; 20. A method or apparatus according to any preceding or following embodiment.

[0157] 35. the biological activity of the pharmaceutical powder in the formed minitablets is at least 90% of the biological activity before compression; 20. A method or apparatus according to any preceding or following embodiment.

[0158] 36. the biological activity of the pharmaceutical powder in the formed minitablets is at least 95% of the biological activity before compression; 20. A method or apparatus according to any preceding or following embodiment.

[0159] 37. The formed minitablets have a density of about 1.00 to 1.15 mg / mm3. 20. A method or apparatus according to any preceding or following embodiment.

[0160] 38. The formed minitablets have a mass of about 1.02 to 1.06 mg / mm 3 having a density of 20. A method or apparatus according to any preceding or following embodiment.

[0161] 39. 1. A method for producing minitablets from a drug comprising at least one of a protein, a peptide, and an antibody for human consumption, comprising: compacting the powder in a first direction with a first movable compacting member and compacting the powder in a second direction with a second movable compacting member to form a compact cylindrical mass of the medicament extending along a longitudinal axis; repeatedly compacting the compact cylindrical mass along the longitudinal axis with a reciprocating cylindrical member together with the first movable compacting member and the second movable compacting member; Includes method.

[0162] 40. The iterative compacting comprises: Repeatedly compacting said compact cylindrical mass into a cylindrical mold. Including, 20. A method or apparatus according to any preceding or following embodiment.

[0163] 41. 1. A method for forming a microscale shaped mass, comprising: providing a material to a filling region of the device, thereby a. extruding the material from the fill region into a forming region of the device; b. compressing the material of the forming region of the device into the microscale feature mass having a perimeter conforming to an inner surface of the forming region; c. ejecting said microscale shaped mass; Initiate automated processes, including Includes method.

[0164] 42. The automated process comprises: Providing material in the fill region Further comprising: 20. A method or apparatus according to any preceding or following embodiment.

[0165] 43. The automated process comprises: Providing said material; extruding said material; The method further comprises the repetitive exercise comprising: the repetitive motion is configured to terminate when the forming region contains a predetermined amount of material. 20. A method or apparatus according to any preceding or following embodiment.

[0166] 44. Each repetition of the repetitive motion comprises: packing the material into the forming area after forcing the material into the forming area; Further comprising: 20. A method or apparatus according to any preceding or following embodiment.

[0167] 45. Discharging the shaped mass. Extending a formation portion of the device including the formation region away from a remainder of the device; pushing the shaped mass away from a first edge of the formation; collecting the shaped mass from a second edge of the formation opposite the first edge; Including, 20. A method or apparatus according to any preceding or following embodiment.

[0168] 46. The microscale shaped mass comprises a therapeutic composition. 20. A method or apparatus according to any preceding or following embodiment.

[0169] 47. The forming portion is cylindrical. 20. A method or apparatus according to any preceding or following embodiment.

[0170] As used herein, the singular terms "a," "an," and "the" may include plural referents unless the context clearly dictates otherwise. Reference to a singular referent is not intended to mean "the only one," unless expressly stated otherwise, but rather "one or more."

[0171] As used herein, the term "set" refers to a collection of one or more objects. Thus, for example, a set of objects can include a single object or multiple objects.

[0172] As used herein, the terms "substantially" and "about" are used to describe and explain small variations. When used with an event or circumstance, the term can refer to not only when the event or circumstance occurs exactly, but also when the event or circumstance occurs in close approximation. When used with a numerical value, the term can refer to a range of variation of ±10% or less of the numerical value, for example, ±5% or less, ±4% or less, ±3% or less, ±2% or less, ±1% or less, ±0.5% or less, ±0.1% or less, or ±0.05% or less. For example, "substantially" aligned can refer to an angle variation in the range of ±10° or less, for example, ±5° or less, ±4° or less, ±3° or less, ±2° or less, ±1° or less, ±0.5° or less, ±0.1° or less, or ±0.05° or less.

[0173] Furthermore, amounts, ratios, and other numerical values ​​may sometimes be presented in the form of a range herein. Such range formats are used for convenience and brevity and should be understood flexibly to include numerical values ​​expressly specified as the limits of the range, but should also be understood to include all individual numerical values ​​or subranges subsumed within the range, as if each numerical value and subrange were expressly specified. For example, a ratio in the range of about 1 to about 200 should be understood to include the range of about 1 to about 200 explicitly recited, but also individual ratios such as about 2, about 3, and about 4, and subranges such as about 10 to about 50, about 20 to about 100, etc.

[0174] The foregoing description of various embodiments of the technology of the present disclosure has been presented for purposes of illustration and description. The foregoing description is not intended to limit the technology of the present disclosure to the precise form disclosed. Many modifications, variations, and improvements will be apparent to those skilled in the art. For example, the device embodiments can be sized and otherwise adapted for various pediatric and neonatal applications, as well as various veterinary applications. They may also be adapted for both male and female urinary tracts. Moreover, those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific devices and methods described herein. Such equivalents are considered to be within the scope of the technology of the present disclosure and are covered by the following appended claims.

[0175] Elements, features, or acts from one embodiment can be readily recombined or substituted with one or more elements, features, or acts from other embodiments to form numerous additional embodiments within the scope of the technology of the present disclosure. Moreover, elements shown or described as being combined with other elements can exist as stand-alone elements in various embodiments. Thus, the scope of the technology of the present disclosure is not limited to the details of the described embodiments, but only by the scope of the appended claims.

Claims

1. 1. A method for producing microtablets from a pharmaceutical powder for human consumption, comprising the steps of: directing the powder in a first direction with a first movable member to form a collected mass of powder at a first density; compacting the collected mass in a second direction with a second movable member to form a compact mass of the powder; and repeatedly compacting the compact mass of powder to gradually increase the density of the compact mass of powder to form a compacted mass of final density and shape of a solid minitablet. method.

2. The method of claim 1 , wherein the compressed mass is a cylindrical mass and extends along a longitudinal axis.

3. The method of claim 2 , wherein the repeatedly compacting comprises repeatedly compacting the cylindrical mass along the longitudinal axis.

4. 3. The method of claim 2, wherein said repeatedly compacting comprises repeatedly compacting said cylindrical mass into a cylindrical die to form said minitablets.

5. The method of claim 1 , wherein the second direction is orthogonal to the first direction.

6. The method of claim 5 , wherein the repeatedly compacting comprises repeatedly compacting the compact mass in a third direction orthogonal to the first direction and the second direction.

7. The method of claim 1 , wherein directing the powder comprises directing the powder using a funnel.

8. The method of claim 1 , wherein the repeatedly compacting comprises repeatedly compacting the compact mass with a reciprocating third compacting member.

9. The method of claim 1 , wherein the pharmaceutical powder comprises large drug molecules having at least one of a protein, a peptide, and an antibody.

10. the pharmaceutical powder comprises a biological activity; the biological activity of the pharmaceutical powder in the formed mini-tablets is at least 70% of the biological activity before compression; The method of claim 1.

11. 10. The method of claim 1, wherein the biological activity of the pharmaceutical powder in the formed minitablets has at least 90% of the biological activity before compression.

12. 10. The method of claim 1, wherein the biological activity of the pharmaceutical powder in the formed mini-tablets has at least 95% of the biological activity before compression.

13. 10. The method of claim 1, wherein the formed minitablets have a density of about 1.00 to 1.15 mg / mm3.

14. 10. The method of claim 1, wherein the formed minitablets have a density of about 1.02-1.06 mg / mm3.

15. 1. A method for producing microtablets from a pharmaceutical powder comprising at least one of a protein, a peptide, and an antibody for human consumption, comprising: compacting the powder in a first direction with a first movable compacting member and compacting the powder in a second direction with a second movable compacting member to form a compact cylindrical mass of the powder extending along a longitudinal axis; and repeatedly compacting the compact cylindrical mass along the longitudinal axis with a reciprocating cylindrical member together with the first movable compacting member and the second movable compacting member. method.

16. The method of claim 15 , wherein the repeatedly compacting comprises repeatedly compacting the compact cylindrical mass in a cylindrical mold.

17. The method of claim 15 , wherein the second direction is orthogonal to the first direction.

18. The method of claim 15 , wherein the repeatedly compacting comprises repeatedly compacting the compact cylindrical mass in a third direction orthogonal to the first direction and the second direction.

19. 1. A method for forming a microscale shaped mass, comprising: providing a material to a filling region of the device, thereby a. extruding the material from the fill region in a first direction with a first movable member into a forming region of the device; b. packing the material into the forming area in a second direction with a second movable member; c. compressing the material in the forming region of the device into the microscale feature mass having a perimeter conforming to an inner surface of the forming region; d. Discharging the microscale shaped mass; Initiating an automated process including method.

20. The method of claim 19 , wherein the automated process further comprises providing the material to the fill area.

21. The automated process comprises: Providing the material; extruding the material; The method further comprises the repetitive exercise comprising:

20. The method of claim 19, wherein the repetitive motion is configured to terminate when the forming region contains a predetermined amount of the material.

22. Discharging the microscale shaped mass, Extending a formation portion of the device including the formation region away from a remainder of the device; pushing the micro-scale feature mass from a first edge of the formation; collecting the micro-scale feature mass from a second edge of the formation opposite the first edge; 20. The method of claim 19, comprising:

23. The method of claim 19 , wherein the microscale shaped mass comprises a therapeutic composition.

24. The method of claim 19 , wherein the forming region is cylindrical.

25. The method of claim 19 , wherein the second direction is orthogonal to the first direction.

26. 26. The method of claim 25, wherein the compressing comprises compressing the material in a third direction orthogonal to the first direction and the second direction.

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