Cartridge-based systems and methods for preparing pharmaceutical compositions

Abstract

Methods, systems, and devices are disclosed for compounding and preparing pharmaceutical compositions using cartridges and computer-controlled dispensing apparatuses. A cartridge containing an active pharmaceutical ingredient and at least one excipient, diluent, or carrier may be processed using a bladeless planetary mixer to disperse the active pharmaceutical ingredient and form a compounded pharmaceutical composition within the cartridge, after which the cartridge is received by a dispensing device configured to dispense metered quantities into a container under software control. The disclosed techniques further enable preparation of topical pharmaceutical compositions and pharmaceutical film dosage forms, including dispensing onto a substrate and drying using an integrated drying mechanism, thereby supporting automated, accurate, and patient-specific pharmaceutical preparation.

Description

Cartridge-Based Systems and Methods for Preparing Pharmaceutical Compositions Cross-Reference to related applications

[0001] The present application claims the benefit of U.S. provisional patent application serial number 63 / 761,213 filed February 21, 2025, and U.S. provisional patent application serial number 63 / 770,095 filed March 11, 2025. The contents of the above-referenced documents are incorporated herein by reference in their entirety.Technical Field

[0002] The present invention pertains to methods, systems, and devices for the formulation of pharmaceutical compositions through the controlled metered dispensing of individual components. More particularly, the invention relates to methodologies, systems, and apparatuses that facilitate the selective preparation of pharmaceutical compositions in customizable and user-defined dosage forms. Such dosage forms may include, but are not limited to, oral, rectal, vaginal, nasal administration forms (e.g., tablets, capsules, troches, transmucosal films, suppositories, gummies, powder blends, or liquids) , topical and transdermal administration forms (e.g., creams, lotions, ointments, or gels) or other types of pharmaceutical dosage forms of which composition include but are not limited to solutions, suspensions, dispersions or emulsions. The invention provides flexibility in tailoring the dosage forms to specific patient needs, therapeutic requirements, or clinical conditions.

[0003] Furthermore, the invention includes advancements in cartridge technology, which enable the effective storage, preservation, and delivery of ingredients for the preparation of pharmaceutical compositions. These cartridges are specifically designed to store and dispense Active Pharmaceutical Ingredients (APIs), diluents, excipients, carriers, stabilizers, binders, and other formulation components.

[0004] The cartridge system of the invention is configured to work synergistically with a device for the automated preparation of pharmaceutical formulations. In a specific and non-limiting example of implementation, the device is equipped with mechanisms to receive cartridges, identify their contents, and selectively meter out predetermined quantities of the stored ingredients. In this example, the process ensures precision in formulation, minimizes the risk of cross-contamination, and reduces human error during preparation. Additionally, the automated system may allow for real-time monitoring, adjustment of ingredient ratios, and adherence to specific pharmaceutical standards.

[0005] The invention also encompasses the integration of digital or electronic control systems for enhanced functionality. For instance, the cartridges may include identification mechanisms, such as RFID tags, QR codes, spectroscopy, or other identifiers, that allow the device to recognize the type, quantity, and expiration date of the stored ingredients. The system may further include software algorithms to optimize formulation processes, log preparation data, and provide user interfaces for customization and monitoring.Background

[0006] Pharmaceutical compounding, which includes applications for both human and veterinary medicine, has been a well-established practice for many years and remains an essential approach for preparing pharmaceutical compositions that are customized to the needs of individual patients. This customization is particularly important in scenarios where commercially available, mass-produced pharmaceutical products do not meet the specific therapeutic requirements of a patient. For instance, commercially manufactured products are often supplied in fixed dosage forms and concentrations, which may not align with the unique dosage form or API concentration required by a particular patient.

[0007] The compounding process typically involves a pharmacist who manually procures, measures, and combines the required ingredients to prepare the desired pharmaceutical formulation. This includes selecting an appropriate dosage form (e.g., topical cream, oral liquid, or mucoadhesive film, etc.) and ensuring accurate measurement and final concentration / dosing of APIs and excipients. However, this traditional approach is labor-intensive, largely manual, and inherently prone to human error. Furthermore, it often demands stringent environmental and procedural controls to ensure safety and accuracy.

[0008] For example, in the preparation of a topical pharmaceutical composition containing a specific API, the pharmacist must accurately weigh the API to achieve the desired concentration. APIs are frequently supplied in powdered form and require precise handling under controlled conditions, such as in a powder containment enclosure, serving as the primary engineering control, further installed within an enclosed production space, serving as the secondary engineering control , to prevent contamination of the environment or exposure to the pharmacist. The precision required for weighing APIs typically extends to the hundredths or even thousands of a gram, necessitating the use of high-accuracy instruments and attention to detail. This process is not only time-consuming but also presents potential risks of error, particularly in busy pharmacy settings where multiple APIs are stored and handled concurrently.

[0009] A compounding pharmacy may work with dozens or even hundreds of different APIs, each with distinct properties, handling requirements, and therapeutic applications. Despite robust labeling and verification protocols, there remains a non-negligible risk of errors, such as selecting the wrong API for a formulation. Such errors, although statistically rare, can have significant implications for patient safety and treatment efficacy. These challenges are further compounded by the manual nature of the compounding process, which relies heavily on the expertise and attention of individual pharmacists.

[0010] To address these longstanding challenges, the compounding industry has increasingly turned to automation as a means of transforming the compounding process. Automated compounding systems are designed to streamline operations, reduce labor intensity, and minimize the potential for human error. These systems integrate advanced technologies, such as precision dispensing mechanisms, ingredient verification systems, and automated mixing equipment, to enable the accurate and efficient preparation of pharmaceutical compositions in their final primary packaging.

[0011] In a specific embodiment of automation in pharmaceutical compounding, automated equipment has been proposed to prepare pharmaceutical compositions, employing principles analogous to those of an inkjet printer. In this embodiment, the device utilizes cartridges containing preloaded pharmaceutical ingredients, which are metered and dispensed in precise amounts to combine the ingredients in the correct proportions, thereby achieving the desired dosage form, composition and strength.

[0012] In one specific example of such automated equipment, the device is configured to deposit precise quantities of pharmaceutical ingredients onto a build platform, in a manner that forms an ingestible dosage unit, such as a capsule. The build platform serves as a substrate upon which the ingredients are layered, dispensed, or otherwise deposited in controlled amounts to create the final dosage form.

[0013] In one exemplary implementation of this approach, the cartridges employed in the device are loaded with an API that is either suspended or dissolved in a suitable carrier medium. The carrier medium is selected based on its ability to solidify upon delivery to the build platform, thereby forming a stable dosage form. For example, the carrier may include polymeric materials, gel-forming agents, or other solidifiable excipients capable of encapsulating the API and maintaining the capsule integrity.

[0014] The dosage of the pharmaceutical composition is determined through volume control, wherein the amount of API-carrier mixture dispensed from the cartridge corresponds to thedesired dose of the API. The device employs control systems to regulate the volume of material discharged from the cartridge, ensuring consistent and reproducible dosing. In some embodiments, the system may allow for the preparation of multi-layered or multi-component dosage forms. For example, the build platform may receive successive layers of different APIs, excipients to create capsules with tailored release profiles or combination therapies.

[0015] In another embodiment of automated equipment for pharmaceutical compounding, the device is configured to produce more complex capsule structures by constructing the dosage form as a three-dimensional (3D) network of materials. In this approach, the final capsule structure is conceptualized as an assemblage of discrete building blocks, with each block comprising either an Active Pharmaceutical Ingredient (API) or a carrier material. The device employs separate cartridges for the API and the carrier, which are dispensed in a controlled manner to form the 3D network layer by layer.

[0016] The 3D construction process involves the precise interspersing of API blocks and carrier blocks within each layer of the network, resulting in a structurally stable and customizable capsule design. This layer-by-layer additive manufacturing approach allows for precise spatial arrangement of the API and carrier materials, enabling the creation of dosage forms tailored to specific therapeutic needs. The density and distribution of API blocks within the 3D network directly determine the dose / concentration of the final capsule. For higher dose / concentrations applications, the density of API blocks in the network is increased, while lower dose / concentrations applications are achieved by reducing the density of API blocks relative to the carrier blocks.

[0017] This approach is not limited to single-API formulations. In certain embodiments, the device can integrate multiple APIs into the same 3D network, enabling the production of combination therapies or multi-functional dosage forms. For example, different API cartridges can be used to deposit distinct API blocks, which may vary in therapeutic function, release profile, or solubility characteristics. These APIs can be spatially distributed within the 3D network in a manner that optimizes their combined therapeutic effect. For instance, one API may be positioned for immediate release, while another API is embedded deeper within the structure for delayed, sustained / slow or extended release.

[0018] The carrier material, dispensed from a separate cartridge, serves multiple functions within the 3D network. It acts as a structural matrix to support the API blocks, ensures the mechanical integrity of the capsule, and may contribute to controlled release mechanisms. The carrier material may be selected from a variety of biocompatible excipients, such as polymers, gel-forming agents, or solidifiable materials, depending on the desired properties ofthe final dosage form. In some embodiments, the carrier material may include additional excipients, such as stabilizers, dispersing agents, or flavorings, to further enhance the capsule’s functionality or patient acceptability.Summary

[0019] This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is not intended to identify key aspects or essential aspects of the claimed subject matter.

[0020] The present invention relates generally to systems, methods, and devices for compounding, dispensing, and preparing pharmaceutical compositions using cartridges, mixing equipment, and computer-controlled dispensing apparatuses. The disclosed subject matter addresses challenges associated with accurate, flexible, and patient-specific pharmaceutical preparation, including the handling of active pharmaceutical ingredients, excipients, diluents, carriers, and base formulations, while enabling automated and controlled dispensing and processing.

[0021] In one aspect, the invention provides a method for compounding a pharmaceutical composition in which an active pharmaceutical ingredient is combined with at least one excipient, diluent, or carrier within a cartridge. The cartridge is placed in a bladeless planetary mixer and subjected to superimposed rotational and revolutionary motion to disperse the active pharmaceutical ingredient within the excipient, diluent, or carrier and thereby form a compounded pharmaceutical composition within the cartridge. Following mixing, the cartridge is removed from the mixer and placed in a computer-controlled dispensing device, which dispenses a metered quantity of the compounded pharmaceutical composition from the cartridge into a container. In some embodiments, mixing parameters such as speed, duration, and temperature may be controlled, and dispensing may be performed in response to user input received via a graphical user interface. The method may be carried out in a pharmacy or compounding facility to prepare patient-specific pharmaceutical compositions.

[0022] In another aspect, the invention provides a system for compounding a pharmaceutical composition. The system includes a cartridge containing an active pharmaceutical ingredient and at least one excipient, diluent, or carrier, a bladeless planetary mixer configured to receive the cartridge and impart superimposed rotational and revolutionary motion to mix the contents of the cartridge, and a computer-controlled dispensing device configured to receive the cartridge after mixing and dispense a metered quantity of the compounded pharmaceutical composition into a container. The system may further include user interface components forcontrolling mixing and dispensing operations, cartridge identification components for associating dispensing parameters with a specific cartridge, and non-transitory machine-readable storage for storing compounding or dispensing parameters. The system may be deployed in a pharmacy, compounding facility, or similar environment to enable automated and repeatable pharmaceutical preparation.

[0023] In a further aspect, the invention provides an adapter for use with a bladeless planetary mixer. The adapter includes a body configured to be received by the mixer and a cartridge interface portion configured to mate with a cartridge containing an active pharmaceutical ingredient and at least one excipient, diluent, or carrier. The adapter retains the cartridge during operation of the mixer such that rotational and revolutionary motion imparted by the mixer is transmitted to the cartridge to facilitate mixing of the contents within the cartridge. In certain embodiments, the adapter may receive the cartridge in a sealed condition, accommodate cartridges of different sizes or volumes, and permit transfer of the cartridge from the mixer to a dispensing device without opening the cartridge. The cartridge may be configured as a single-dose or multi-dose cartridge and may contain liquid or semi-solid pharmaceutical compositions.

[0024] In another aspect, the invention provides a method for making a topical pharmaceutical composition. In accordance with this aspect, an active pharmaceutical ingredient in solution is dispensed from a cartridge using a computer-controlled dispensing device into a container. The container comprises a metering mechanism configured to dispense the resulting topical pharmaceutical composition to a patient in controlled doses. In some embodiments, a pharmaceutically acceptable base formulation, such as a cream, gel, ointment, lotion, paste, emulsion, or foam, may be dispensed into the container before or after dispensing the active pharmaceutical ingredient solution. The contents of the container may then be mixed, optionally using a planetary mixer, to form a homogeneous topical pharmaceutical composition. Dispensing operations may be controlled by software executed by the dispensing device, which may receive user input, apply patient-specific parameters, store dispensing information, and generate records for compliance, traceability, or quality control.

[0025] In a further aspect, the invention provides a method for manufacturing a pharmaceutical film dosage form. In this aspect, a cartridge containing an active pharmaceutical ingredient together with at least one excipient, diluent, or carrier is placed in a computer-controlled dispensing device that includes both a dispensing head and a drying mechanism integrated with the dispensing device. The dispensing head dispenses a controlled quantity of the cartridge contents onto a substrate, and the drying mechanism removes solvent or moisture from the dispensed material to dry the material and form apharmaceutical film dosage form. The dispensing and drying operations may be coordinated under software control. In some embodiments, the dispensing may be performed according to a predefined pattern to control film geometry, thickness, or dosage strength, and the resulting film dosage form may be a mucoadhesive film, may be separated into individual doses, and may be patient-specific.

[0026] As described herein, the disclosed systems and methods are based on a cartridgebased approach for dispensing, mixing, and preparing pharmaceutical compositions, wherein one or more cartridges containing active pharmaceutical ingredients and / or pharmaceutically acceptable excipients, diluents, carriers, or base formulations are processed using computer-controlled dispensing apparatuses. While certain embodiments are described in the context of additive manufacturing or layer-by-layer deposition of pharmaceutical compositions, such embodiments are provided as illustrative examples only. The invention is not limited to additive manufacturing techniques, and encompasses non-additive dispensing, batch dispensing, volumetric dispensing, and post-dispense mixing workflows, including embodiments in which pharmaceutical compositions are dispensed into containers and subsequently mixed or processed without forming structures in a layer-by-layer manner. Accordingly, additive manufacturing represents one optional implementation within the broader concept of cartridge-based pharmaceutical dispensing and compounding.

[0027] All features of embodiments which are described in this disclosure and are not mutually exclusive can be combined with one another. Elements of one embodiment can be utilized in the other embodiments without further mention. The foregoing summary is intended to provide an overview of certain aspects of the invention and is not intended to limit the scope of the invention, which is defined by the appended claims. Additional features, embodiments, and variations will be apparent to those skilled in the art upon review of the detailed description and the accompanying drawings.Brief Description of the Drawings

[0028] For a better understanding of the various embodiments described herein, and to show more clearly how these various embodiments may be carried into effect, reference will be made, by way of example, to the accompanying drawings which show at least one example embodiment, and which are now described. The drawings are not intended to limit the scope of the teachings described herein. In the drawings:

[0029] FIG. 1 illustrates a schematic representation of a device configured for the additive manufacturing of pharmaceutical compositions. The device incorporates one or more cartridges for dispensing materials from which the pharmaceutical composition is to be made.

[0030] FIG. 2 provides a schematic depiction similar to FIG. 1, detailing the progressive construction of a pharmaceutical composition in solid form, achieved through the sequential deposition of material in a layer-by-layer fashion.

[0031] FIG. 3 presents a block diagram outlining the principal functional components of the device depicted in FIG.s 1 and 2. This diagram provides an overview of the core modules and their operational interrelationships.

[0032] FIG. 4 illustrates a block diagram that delineates relationships among functional components of the device in FIG.s 1 through 3, with a particular focus on their interaction with a Graphical User Interface (GUI).

[0033] FIG. 5 depicts a visual representation of various control elements within a GUI pane, designed to enable the operation and control of the device shown in FIG.s 1 through 3.

[0034] FIG. 6 shows a GUI pane populated with a plurality of interactive controls, allowing the user to execute various operational functions associated with the device.

[0035] FIG. 7 illustrates a hierarchical structure within the GUI, enabling the user to select from a plurality of pre-defined dosage forms for manufacturing.

[0036] FIG. 8 provides a flowchart detailing the operational workflow of the device illustrated in FIG.s 1 through 3, outlining the sequence of steps required to manufacture pharmaceutical compositions.

[0037] FIG. 9 is a schematic perspective view of a bladeless planetary mixer. The illustration shows the mixer with its cover open, revealing a basket configured to receive a container designed for holding ingredients to be mixed.

[0038] FIG. 10 is a perspective, exploded view of a first example of a container suitable for mixing ingredients within the planetary mixer depicted in FIG. 9.

[0039] FIG. 11 is a perspective view of an adapter designed to facilitate the secure mounting of the container shown in FIG. 10 into the basket of the planetary mixer.

[0040] FIG. 12 illustrates the container of FIG. 10 mounted within the adapter described in FIG. 11, demonstrating the integrated configuration.

[0041] FIG. 13 shows a perspective view of a second example of a container designed for ingredient mixing in the planetary mixer described in FIG. 9.

[0042] FIG. 14 depicts an adapter specifically configured for mounting the container of FIG.13 into the basket of the planetary mixer shown in FIG. 9.

[0043] FIG. 15 is a perspective view of a third example of a container that can be employed for ingredient mixing in the planetary mixer of FIG. 9. Additionally, FIG. 15 illustrates one half of the corresponding adapter for this container. The other half of the adapter, being a mirrored counterpart, is not shown but is understood to complete the mounting assembly.

[0044] FIG. 16 presents a schematic view of a cartridge designed for use with the device shown in FIG.s 1 through 3. The cartridge enables the dispensing of metered quantities of ingredients for the preparation of pharmaceutical compositions.

[0045] FIG. 17 depicts a variant of the cartridge shown in FIG. 16, which utilizes a remotely mounted reservoir to supply ingredients to the dispensing mechanism.

[0046] FIG. 18 illustrates another variation of the cartridge shown in FIG. 16. This version is pre-loaded with an ingredient in powder or solid form, allowing the userto add a carrier, diluent, or excipient prior to utilizing the cartridge in the device shown in FIG.s 1 through 3.

[0047] FIG. 19 provides a perspective view of yet another variant of the cartridge shown in FIG. 16. This configuration includes multiple compartments for segregating a first ingredient in solid form and a second ingredient in liquid form. The compartments are separated by a removable or deactivatable partition, enabling the ingredients to be mixed to form a suspension or solution immediately before use.

[0048] FIG . 20 is a flowchart of a process for automatically dispensing one or more ingredients from the device shown in FIG. 1 in a container, which are then mixed using the bladeless planetary mixer of FIG. 9. Note that optional steps are denoted by dashed lines.

[0049] FIG. 21 is flowchart of a process for homogenizing the ingredients in cartridge by using a bladeless planetary mixer. Optional steps are denoted by dashed lines.

[0050] FIG. 22 is a schematic representation of a cartridge incorporating a separable metering mechanism, illustrating its structural and functional components.

[0051] FIG. 23 depicts multiple cartridges designed based on the principle of a syringe, showcasing variations in their construction and potential applications.

[0052] FIG. 24 provides a schematic representation of a syringe-based cartridge, detailing its interaction with dispensing mechanisms and highlighting key operational features.

[0053] FIG. 25 is a top plan view of a mold for making transmucosal films, using the device according to the present invention.

[0054] FIG. 26 is a side elevational view of the mold shown in FIG. 25.

[0055] FIG.s 27 to 30 illustrate different deposition patterns of a composition in a mold.

[0056] FIG. 31 is flowchart of a process for making a transmucosal film.Detailed description

[0057] FIG. 1 provides a high-level schematic illustration of a device (designated as device 10) for the additive manufacturing of pharmaceutical compositions. This device is configured to produce pharmaceutical compositions in a variety of dosage forms, including but not limited to capsules for oral ingestion, mucoadhesive films, suppositories, topicals, and potentially other formats. The flexibility of the device allows it to cater to both human and veterinary applications. In a typical implementation, the pharmaceutical compositions fabricated by the device incorporate an Active Pharmaceutical Ingredient (API), which is dispersed within a suitable excipient, carrier, or diluent to form the final dosage form.

[0058] The device 10 comprises a structural frame (frame 1), which serves as the primary support structure for the various operational components. This frame ensures the stability and precision required for the additive manufacturing process. Mounted atop the frame 1 is a build platform 2, which provides the surface upon which the pharmaceutical composition is constructed layer by layer.

[0059] The build platform 2 is configured to be vertically movable, facilitating precise control over the deposition of ingredients during the manufacturing process. The vertical movement of the platform, as indicated by the double-headed arrow (arrow 4), can be controlled in either an upward ordownward direction. This movement is achieved through mechanisms designed to provide fine resolution and stability, ensuring the accurate placement of each layer. Examples of mechanisms suitable for this vertical displacement include : (1) Screw-based mechanisms, where a threaded screw engages with a nut fixed to the platform, allowing controlled elevation or descent via rotational actuation; (2) Linear actuators, which use motorized drive systems to achieve smooth and precise vertical motion; (3) Alternative mechanisms, such as rack-and-pinion systems or hydraulic actuators, may also be employed depending on the specific requirements of the implementation.

[0060] In certain embodiments, the build platform 2 may be equipped with a heating arrangement to impart thermal energy to the deposited ingredients. This heating capability serves several functions:1. Temperature Control: Maintaining the ingredients at a specific temperature to achieve desired chemical or physical properties during and after deposition.2. Controlled Cooling: Preventing excessively rapid cooling of the deposited materials, which could lead to undesirable effects.3. Facilitating Reactions: Promoting specific thermal reactions or phase transitions.

[0061] The heating arrangement associated with the build platform 2 may include: (1) Resistive filaments: These are integrated into or bonded to the surface of the platform. When an electrical current passes through these filaments, heat is generated due to electrical resistance. The arrangement may include a temperature sensor and feedback loop to maintain precise temperature control; (2) External heating elements: Such as ceramic heaters or infrared emitters, positioned beneath or adjacent to the platform, which transfer heat to the platform surface; (3) Embedded heating circuits: Directly fabricated within the build platform material for uniform thermal distribution across its surface.

[0062] Directly positioned above the build platform 2 is an ingredient dispensing head 3, which is operatively configured to deliver metered quantities of ingredients to the build platform 2. The dispensing head 3 plays an important role in the additive manufacturing process by enabling the precise deposition of ingredients in controlled amounts. This functionality facilitates the production of a pharmaceutical composition in either a final form — ready for patient use — or an intermediary form, which may require additional post-processing steps, such as mixing or homogenization, to achieve a state suitable for patient administration.

[0063] The ingredient dispensing head 3 is designed to ensure high precision in the metering and deposition of pharmaceutical ingredients. This precision is beneficial for maintaining the desired composition and dose accuracy of the pharmaceutical product. In a specific and nonlimiting example, the dispensing head 3 is configured for delivering ingredients in a liquid state within a range of viscosities.

[0064] As. Indicated above, the dispensing head 3 is configured to directly produce pharmaceutical compositions in their final form, suitable for immediate use by the patient without the need for further processing. Examples of final forms include capsules for oral ingestion, wherein the dispensing head 3 deposits the active pharmaceutical ingredient (API)and excipients layer by layer into a preformed capsule shell, or directly forms a solid dosage within the device, mucoadhesive films, where the dispensing head 3 delivers ingredients to create thin, adhesive layers with uniform API distribution, suppositories, in which the device forms the complete dosage unit by sequentially layering the required composition.

[0065] For certain pharmaceutical compositions, particularly those intended for topical applications, the device 10 is configured to produce an intermediary form of the composition. In these instances, the dispensing head 3 delivers one or more ingredients of the composition in a state that requires subsequent processing, such as mixing, to achieve uniformity and usability. For example, the dispensing head 3 may deposit a base formulation, such as a cream or gel, onto a container, followed by the addition of an active ingredient, which typically is in a liquid state. The resulting intermediate mixture in the container may then be homogenized externally using a mixing mechanism, such as a planetary mixer. In a possible variant, a container holding the base formulation is loaded into the device 10 and the device 10 is used to dispense a controlled amount of active ingredient into the container, via the dispensing head 3. The resulting intermediate product is them homogenized in a mixer to provide the final topical preparation.

[0066] In the example shown in FIG. 1, the dispensing head 3 is equipped with multiple nozzles, each dedicated to dispensing specific ingredients. This modular configuration supports the simultaneous or sequential delivery of APIs, excipients, and other formulation components, enhancing the device’s versatility and operational efficiency. In the example shown, the dispensing head carries three cartridges 7, each cartridge having a respective dispensing nozzle 8 to discharge metered amounts of the ingredient from the respective cartridge, it being understood that the dispensing head may incorporate more or less than three ingredient cartridges 7. The structure and operation of the cartridges will be described in greater detail later.

[0067] The dispensing head is operatively configured to facilitate movement within the X-Y plane relative to the build platform (with vertical movement, denoted by arrow 4, corresponding to motion along the Z-axis). This relative movement may be achieved through various configurations, including but not limited to: (1) translating the dispensing head in the X-Y plane while maintaining the build platform stationary; (2) translating the build platform in the X-Y plane while keeping the dispensing head stationary; or (3) enabling simultaneous movement of both the dispensing head and the build platform within the X-Y plane.

[0068] Such configurations are designed to precisely position the dispensing head in relation to the build platform, thereby enabling accurate deposition of material discharged from any ofthe cartridges (e.g., cartridge 7) onto the build platform. This precision in material deposition facilitates the controlled construction of a pharmaceutical preparation or dosage form.

[0069] FIG. 2 illustrates an embodiment similar to that shown in FIG. 1, with the addition of material deposited on the build platform in the form of distinct layers, designated as layers 9. In the depicted example, four layers 9 are shown; however, it is to be understood that the number of deposited layers may vary, and any number of layers, greater or fewer than four, can be deposited in a stacked configuration to construct a pharmaceutical preparation. The depicted configuration exemplifies a pharmaceutical preparation suitable for oral dosage forms, which, upon completion of the layering process, is ready for use. Specifically, the oral dosage form is structured for direct ingestion by a patient.

[0070] For pharmaceutical preparations intended for topical application, where subsequent mixing is required to homogenize the formulation and ensure uniform distribution of the active pharmaceutical ingredient (API) within a base formulation, layered deposition is not necessarily required. In such instances, the system may be configured to accommodate a preprovided container containing the base formulation. This container, which is not shown in the drawing, may initially be prepared outside the device (e.g., device 10) and subsequently placed on the build platform 2.

[0071] In this configuration, the dispensing head 3 is adapted to deliver metered quantities of a selected API from the respective cartridge 7 directly onto the base formulation contained within the container. Unlike the layered approach, the dispensing in this scenario may not require precise stacking or layering since a subsequent mixing step ensures homogenization of the mixture. During such a dispensing operation, the dispensing head 3 may remain stationary relative to the build platform 2 and, consequently, stationary relative to the container.

[0072] Alternatively, the system may be configured to enable relative motion between the dispensing head 3 and the build platform 2 to distribute the discharged ingredient more uniformly over the surface area of the base formulation within the container. This relative motion ensures that the ingredient is not deposited at a single point but rather is evenly distributed over the container’s surface. Such movement is precisely controlled to ensure that the discharged material remains confined within the boundaries of the container, preventing spillage or uneven distribution outside the desired area.

[0073] This flexibility in material deposition — whether by layered stacking for oral dosage forms or surface-level distribution for topical dosage forms or any other suitable dosage form —allows the system to accommodate a wide range of pharmaceutical preparations, enhancing its versatility for different dosage form requirements.

[0074] For topical pharmaceutical preparations where a container is placed on the build platform 2 to receive ingredients dispensed from the dispensing head 3, a suitable retention fixture can be provided on the build platform 2 to securely mount the container. This fixture is designed to maintain the stability of the container during the dispensing operation, thereby preventing unintended movement or displacement of the container relative to the build platform 2.

[0075] The fixture may comprise any suitable structural arrangement or mechanism configured to engage and hold the container securely in place on the build platform 2. Examples of such fixtures include, but are not limited to, clamping mechanisms, recessed holders, vacuum-based retention systems, magnetic couplings (where applicable), or interlocking grooves or slots specifically designed to accommodate the container’s shape and size.

[0076] The primary purpose of the fixture is to ensure that the positional registration of the container relative to the dispensing head 3 is accurately maintained throughout the ingredient dispensing process. By fixing the container in a predetermined and known position, the system can ensure that the material discharged from the dispensing head 3 is confined within the boundaries of the container, thereby preventing spillage or misplacement of the ingredients.

[0077] Additionally, the fixture may be adjustable or interchangeable to accommodate containers of varying sizes and shapes, thereby increasing the system’s versatility and enabling its use with a wide range of container types. Such adjustability may be achieved through modular components, adjustable brackets, or similar mechanisms that allow for rapid reconfiguration of the fixture to suit specific application requirements.

[0078] In some embodiments, the fixture may further include sensors or alignment guides to confirm the correct positioning of the container prior to the dispensing operation. These features enhance operational reliability and precision, ensuring that the dispensing process is conducted accurately and efficiently while minimizing the risk of errors associated with container misalignment or instability.

[0079] FIG. 3 presents a block diagram of the device (10), illustrating the primary functional components of the device. The device (10) comprises a user interface (12), one or more sensors (20), a processing unit (14), a dispensing head control unit (18) and a drive unit (16). The user interface (12), the one or more sensors (20), the processing unit (14) and thetemperature regulation unit (18) form a control arrangement which regulates the operation of the device 10, in particular, the control arrangement regulates the operation of the drive unit 16 performs the relative motion between the dispensing head 3 and the build platform in a coordinated fashion in the three dimensions, namely coordinated movements along the X, Y and Z axes..

[0080] The user interface (12) enables a user to control the device (10), specifically to input commands to manage the operation of the machine and to receive information regarding the machine's operation.

[0081] In one specific embodiment, the user interface (12) may be a graphical user interface (GUI), which employs graphic controls to accept user inputs and communicate information to the user. This GUI can be implemented on a touch-sensitive screen. Other forms of implementation are possible without departing from the scope of the invention, such as using a pointing device instead of a touch-sensitive surface.

[0082] The user interface (12) communicates with a processing unit (14) that performs the main data processing functions of the device (10). The processing unit (14) typically comprises a computer architecture with a central processing unit (CPU) and suitable interfaces to receive data inputs and output data as commands to regulate the operation of the device (10). The computer architecture also includes storage means to store computer code, which comprises machine instructions executed by the CPU to implement the various functions of the planetary mixer (10).

[0083] The planetary mixer (10) further comprises a driving unit (16) operatively configured to facilitate relative displacement between the build platform (2) and the dispensing head (3). The driving unit (16) is designed to enable precise and controlled motion along multiple axes, allowing for coordinated movement necessary to achieve accurate material deposition.

[0084] At a high level, the driving unit (16) incorporates a plurality of drive motors (not illustrated in the figures), typically one dedicated to each axis of motion. These drive motors are operatively connected to motion transmission components, which may include, but are not limited to, linear actuators, belts, pulleys, gear systems, or lead screws. These components are arranged to generate and transmit mechanical motion in a coordinated manner, enabling three-dimensional movement between the build platform (2) and the dispensing head (3).

[0085] The drive unit (16) is configured to provide precise control over the movement parameters, including position, speed, and acceleration, thereby ensuring that the relative positioning between the dispensing head (3) and the build platform (2) meets the operationalrequirements of the device. This design ensures that material discharged by the dispensing head (3) is deposited at precise locations on the build platform (2), facilitating the accurate construction of pharmaceutical preparations or other desired formations.

[0086] The sensors (20) include one or more sensing components operatively configured to monitor the operational condition of the device (10). In one embodiment, the sensors (20) comprise a weight sensor operatively coupled to the build platform (2) to detect and measure the weight of materials or objects placed thereon. Such objects may include, for example, a container positioned on the build platform (2) to receive an ingredient dispensed from the dispensing head (3). The weight sensor provides output signals representing the measured weight, which can be utilized to regulate and control the operation of the dispensing head (3) during the dispensing process including able to tare (zero the weight) of a container placed on the build platform.

[0087] In one exemplary configuration, the dispensing head (3) operates as a continuous dispensing type, capable of producing a steady flow of the selected ingredient. The weight sensor monitors the incremental increase in weight on the build platform (2) as material is deposited and generates corresponding output signals conveying real-time weight information. These signals are directed to and processed by a processing unit (14), which compares the measured weight to a predefined target weight. Upon determining that the target weight has been achieved, the processing unit (14) issues a control command to the dispensing head (3) to cease material flow, thereby ensuring precise delivery of the desired quantity of the ingredient.

[0088] In an alternative embodiment, the dispensing head (3) is configured to operate in a metered jet-dispensing mode, wherein the ingredient is discharged as a series of discrete jets. Each jet corresponds to a predetermined and tightly controlled volume of the ingredient. Similar to the continuous flow configuration, the weight sensor monitors the cumulative weight of the material deposited on the build platform (2) and provides weight information to the processing unit (14). The processing unit (14) regulates the successive jet discharges and halts the operation of the dispensing head (3) once the target weight is reached.

[0089] Alternatively, in the jet-dispensing mode, the total amount of discharged material may be determined and managed by counting the number of jet discharges. Given the high precision and tight tolerances associated with the volume of each jet, the processing unit (14) may calculate the cumulative material volume by tracking the number of discharges and terminate the dispensing operation when the total volume matches the desired amount.

[0090] Additionally, the planetary mixer (10) incorporates a dispensing head control unit (18) to regulate the dispensing of ingredients. The dispensing head control unit 18 is responsive to control signals issued by the processing unit 14, as described at high level above, to control the dispensing of ingredients out of the cartridges 7.

[0091] FIG. 2 presents a block diagram providing additional details of the user interface arrangement (12) of the device (10). The user interface arrangement (12) comprises a graphical user interface (GUI) pane (22), which represents the area where the various graphical controls of the GUI are implemented. These controls may include, but are not limited to, text boxes to accept alphanumeric characters as user input, radio buttons, checkboxes that can be selectively activated by the user, menu items, and other graphical controls.

[0092] The GUI outputs signals in response to user input. These signals are communicated to the processing unit (14), where they are managed by a GUI manager (24). The GUI manager (24) is implemented by software executed by the CPU of the processing unit (14). The GUI manager (24) receives the signals generated from the interaction between the user and the GUI, processes these signals as necessary, and conveys them to other functional modules of the device (10) to implement the user commands.

[0093] Additionally, the user interface (12) facilitates the communication of information regarding the processing conditions of the device (10) to the user via the GUI through the GUI manager (24). Specifically, signals conveying information intended to be communicated through the GUI are received by the GUI manager (24). These signals undergo processing, which may include formatting or any other suitable processing, to ensure the information is adequately displayed on the GUI pane (22). Subsequently, the processed signals are conveyed to the GUI pane (22) to activate the necessary display elements of the GUI.

[0094] Referring now to FIG. 3, which illustrates a more specific example of the implementation of the Graphical User Interface (GUI) pane 22, various graphical controls on the GUI pane 22 are arranged within a window. This window includes a menu control 26, which can be activated by touch to display a number of selectable options. These options allow the user to choose from various functionalities associated with the device 10. When the menu is in its expanded condition, as shown in FIG. 6, it presents multiple selectable options, each corresponding to a specific predetermined functionality of the device (10).

[0095] The menu includes, but is not limited to, the following options: preparing composition, dispensing and dispensing ingredient, among others. For instance:

[0096] Preparation of Pharmaceutical Composition

[0097] In this function, the device (10) produces the pharmaceutical composition in a final state suitable for direct use without requiring substantial post-processing steps. Specifically, a pharmaceutical composition in its final state is characterized by the desired amount of an active pharmaceutical ingredient (API) being accurately incorporated into a precise quantity of an excipient, carrier, or diluent to achieve a final dosage. In this state, the active ingredient is substantially uniformly dispersed throughout the excipient, carrier, or diluent, ensuring homogeneity and therapeutic consistency.

[0098] The prepared pharmaceutical composition is immediately ready for use, subject only to minor post-processing steps, such as drying, packaging, or other minimal finishing processes that do not alter the fundamental characteristics of the composition. For example, in cases where the pharmaceutical composition comprises a transdermal film, such as a transmucosal film, for instance a mucoadhesive film, additional drying may be necessary. The mucoadhesive film may initially be constructed on the build platform (3) in a semi-solid or viscous state, and subsequent drying is required to achieve the appropriate consistency for application to mucosal surfaces.

[0099] In one embodiment of the present invention, the drying step required for the preparation of a mucoadhesive film can be executed using the heating capability of the build platform (3). In this configuration, the pharmaceutical composition preparation process includes a drying cycle wherein the temperature of the build platform (3) is precisely controlled to facilitate the drying of the material deposited on the build platform. Alternatively, the heating functionality may incorporate a heated air circulation system, either as a standalone mechanism or in conjunction with the heating of the build platform. The heated air circulation system comprises a heating source, such as one or more heating elements strategically positioned within an airflow path to generate and direct a controlled circulation of heated air around the build platform. The airflow path may be configured to ensure uniform heat distribution, thereby promoting consistent drying across the entire surface of the manufactured product. A vacuum system may also be provided to suck out moist air from the enclosure.

[0100] The temperature of the circulating heated air may be regulated through an integrated control system, either in coordination with or independently of the build platform heating system. This independent or combined temperature regulation allows for optimization of the drying process based on the specific requirements of the material being processed. In particular, for applications involving the manufacture of transmucosal films, as described in greater detail below, heated air circulation has been observed to be an effective means of facilitating film drying. The application of heated air expedites moisture evaporation, reducesdrying time, and enhances the uniformity of the final product by preventing localized overheating that may occur with direct contact heating methods.

[0101] The airflow system may further incorporate adjustable air velocity controls and directional vents to refine the drying process. Additionally, the heating source may be equipped with temperature sensors and feedback loops to dynamically adjust the heat output, maintaining a predetermined drying profile suited to the composition and thickness of the film being processed.

[0102] In some implementations, the heated air circulation system may be supplemented with a dehumidification mechanism to further enhance drying efficiency. By reducing ambient humidity within the processing chamber, the rate of moisture removal from the film is increased, improving throughput and ensuring product consistency.

[0103] The temperature regulation and duration of the drying cycle are managed by the processing unit (14), which is operatively configured to monitor and adjust the drying parameters in real time. The processing unit (14) may implement a variable temperature profile during the drying cycle, wherein the temperature is dynamically adjusted to optimize the drying process. For example, an initial higher temperature may be used to accelerate the removal of moisture, followed by a lower holding temperature to ensure uniform drying and prevent overheating or degradation of the mucoadhesive film.

[0104] The parameters of the drying cycle, including the temperature, time duration, and rate of temperature change, can be customized based on specific factors such as the volume, weight, or thickness of the mucoadhesive film. For instance, larger volumes or thicker films may require extended drying times or adjusted temperature profiles to achieve consistent drying throughout the material.

[0105] The build platform (3) may include integrated sensors, such as temperature sensors or moisture sensors, to provide real-time feedback on the drying conditions. These sensors enable the processing unit (14) to make precise adjustments to the drying cycle, ensuring that the final product achieves the desired consistency, mechanical stability, and adhesion properties required for its intended application.

[0106] This embodiment eliminates the need for external drying equipment, streamlining the manufacturing process and enhancing the efficiency of mucoadhesive film production.

[0107] Dispense Ingredient Function for Topical Pharmaceutical Preparations

[0108] The Dispense Ingredient function is specifically designed for applications in which a topical pharmaceutical preparation is to be produced in an intermediate state. This intermediate state requires a subsequent homogenization step to achieve the final state, wherein the preparation is ready for its intended use. This function does not use the additive building capability of the machine, rather it relies on the capability of the device (10) to dispense precise amounts ingredients, in particular active ingredients.

[0109] In this operational mode, the device (10) is configured to dispense one or more ingredients, such as an active pharmaceutical ingredient (API), into a container. The container may be pre-loaded with an excipient, carrier, or diluent (e.g., a cream or gel) prior to the dispensing of the API. Alternatively, the container may initially be empty and receive only a preset amount of the active ingredient during the dispensing process. In such cases, the excipient, carrier, or diluent can be added to the container in a subsequent step.

[0110] The subsequent addition of the excipient, carrier, or diluent may be performed within the device (10). For example, one or more of the loaded cartridges (7) may dispense the excipient, carrier, or diluent through the dispensing head (3). The dispensing head 3 may operate to discharge both the API and the excipient, carrier, or diluent sequentially or simultaneously, depending on the process requirements. This integrated approach allows for efficient ingredient addition and precise control over the amounts dispensed.

[0111] Alternatively, the addition of the excipient, carrier, or diluent may be performed as a post-processing step outside of the device (10). In this scenario, the container, after receiving the API within the device (10), is removed and processed using conventional techniques to add the required excipient, carrier, or diluent.

[0112] In all instances, once the container contains both the active ingredient(s) and the excipient, carrier, or diluent, it undergoes a mixing post-processing step to ensure uniform dispersion of the API throughout the formulation. This homogenization step is preferably performed in a bladeless planetary mixer, which subjects the container to superimposed revolution and rotation movements. This type of mixing provides several advantages, including: (1) Uniform Dispersion: Ensures that the active ingredient is homogeneously distributed throughout the excipient, carrier, or diluent; (2) Deaeration: Effectively removes entrapped air or gas from the formulation, thereby improving the consistency, stability, and quality of the final product; (3) The bladeless mechanism prevents mechanical degradation or shearing of sensitive components within the formulation, and allows carrying out the mixing directly in a container provided with a metering mechanism, allowing to discharge metereddoses of the topical preparation, which is the container that the patient uses to dispense the topical preparation.

[0113] Each of these functions is selectable via the touch-activated menu control 26, providing the user with a versatile and efficient interface to control the operations of the planetary mixer.

[0114] FIG. 7 illustrates the main structural elements of the Graphical User Interface (GUI) implemented in the device (10), providing enhanced user interaction and control over the device’s functions. When the user activates the Preparing Composition function by selecting the corresponding control on the GUI, the interface transitions to display a dedicated pane (22). This pane includes a Dosage Form Selection Control (28) and an associated Submenu Structure (30). The submenu structure offers selectable options for a range of dosage forms. While the illustrated embodiment includes four dosage forms, it is to be understood that additional dosage forms can be incorporated into the submenu structure without departing from the scope or spirit of the invention.

[0115] In instances where the Dispense Ingredient function is selected, the GUI dynamically invokes a corresponding menu structure that enables the user to input and configure parameters associated with the dispensing operation. These parameters include, but are not limited to, the following:1. Selection of the Active Ingredient

[0116] The GUI provides controls enabling the user to select the specific active ingredient (API) to be dispensed. This selection is facilitated through a list of ingredients currently loaded into the dispensing head (3). The list may display the ingredients by name, chemical identifier, or other suitable labels, offering clear and intuitive identification of the available options. The GUI control dynamically updates to reflect the current inventory of ingredients loaded in the dispensing head (3), ensuring accurate selection.

[0117] Alternatively, the selection may be made based on the cartridge position within the dispensing head (3), allowing the user to input or select the corresponding cartridge slot number.2. Specification of Ingredient Amount

[0118] The GUI includes a text box, numerical input field, or other suitable control for specifying the precise amount of the ingredient to be dispensed. The quantity can be defined in terms of weight (e.g., milligrams) or volume (e.g., milliliters), depending on the specific requirements of the formulation. The input parameters are transmitted to the processing unit(14), which regulates the dispensing operation to ensure that the specified amount is delivered accurately.3. Container Type Selection

[0119] The GUI provides functionality for selecting the type of container in which the ingredient will be dispensed. This container selection can be made via a dropdown menu, list, or pictogram interface, where each container type is identified by a name, icon, or other visual identifier. Examples of containers suitable for use with the device (10) are depicted in FIG.s 10, 13, and 15.

[0120] The selected container type is used by the processing unit (14) to determine the appropriate positioning of the build platform (3) relative to the dispensing head (3). This ensures that the dispensing operation avoids interference between the container and the dispensing head, particularly for containers with varying dimensions or geometries.

[0121] Moreover, the container type selection allows the processing unit (14) to control the drive unit (16) to manage any relative movement between the dispensing head (3) and the container during the dispensing cycle. This control ensures that the dispensing operation is confined within the container’s boundaries, preventing spillage or uneven distribution of the dispensed material.Preparation of a transdermal film

[0122] Referring now to FIG. 8a, a flowchart illustrates an exemplary sequence of steps executed by the device (10) for the preparation of a composition, specifically a transdermal film, such as a transmucosal film, which may be oral, vaginal or otherwise. In a specific example, the film is a mucoadhesive film. The described method enables precise control over the preparation and dispensing of the film to meet predetermined specifications.

[0123] The process begins at step 32, where the device (10) is initialized. At step 34, the graphical user interface (GUI) pane depicted in FIG. 5 is activated. This GUI serves as the primary interface for user interaction. At step 36, the device receives input from the user via the GUI. Following this, at step 38, the GUI transitions to the pane shown in FIG. 6, which presents a list of selectable functions. These functions may include, but are not limited to, “Prepare Composition” and “Dispense Ingredient.” It is understood that additional functions may be incorporated into the GUI without deviating from the scope of the invention.

[0124] At step 40, the user selects the desired function to be performed by the device (10). In the present example, the “Prepare Composition” function is selected. Subsequently, at step42, the GUI depicted in FIG. 7 is displayed, which enumerates various dosage form options. At step 44, the user selects a specific dosage form. For the purposes of this example, the user selects “mucoadhesive film,” which is represented as the last option in the menu of FIG. 7.

[0125] At step 46, the user inputs additional parameters via GUI controls (not explicitly shown). These parameters may include the quantity of mucoadhesive film to be prepared, which can be expressed in terms of weight, volume, or other suitable units, such as discrete film units. Each film unit may correspond to a predetermined weight or volume and represents a single-dose form. Additional user-defined parameters may include the number of film units to be prepared, as it will be discussed in more details below.

[0126] Upon receiving the specified parameters, the device (10) operates the dispensing head (3) at step 48 to dispense the mucoadhesive film composition in accordance with the input parameters. The dispensed composition is in a homogenized state, wherein the active ingredient is substantially uniformly distributed throughout the excipient, carrier, or diluent.

[0127] To achieve this homogenization, the dispensing head (3) houses a cartridge (7) preloaded with the mucoadhesive composition in a homogenized state. The dispensing head (3) precisely meters and discharges the composition from the cartridge (7) based on the selected parameters, such as the specified quantity or number of film units. The composition is deposited onto the build platform (2), or, optionally, into mold cavities provided for casting the mucoadhesive film into usable finished units.

[0128] The mold, if utilized, may include a plurality of mold cavities corresponding to individual film units. An individual film unit may be a single dose. The dispensing head (3) deposits metered amounts of the composition into each mold cavity, forming discrete film units. Additionally, if molds are employed, an optional user-input parameter may specify the arrangement of the mold cavities to ensure precise alignment of the build platform (2) with the dispensing head (3) during the casting of each film unit.

[0129] Upon completion of the dispensing operation, the process transitions to step 52, where a heating function is performed. This heating function facilitates the curing or setting of the dispensed mucoadhesive composition and is implemented via heating elements integrated into the build platform (2). The heating elements operate under feedback control based on temperature and / or humidity data collected from respective sensors.

[0130] A mucoadhesive compositions suitable for use in this process are disclosed in International Patent Application W02021056109 filed by Medisca Pharmaceutique Inc., the contents of which are incorporated herein by reference in their entirety.

[0131] FIG. 26 illustrates a top plan view of a mold (700) configured for use with device (10) in the manufacture of mucoadhesive film units. The mold (700) comprises a plurality of mold cavities (702, 704, 706, 710, and 712), which are designed to receive a predetermined volume of a mucoadhesive composition. The mold (700) further includes a peripheral flange (714) that surrounds and extends outwardly from the mold cavities (702 - 712). The flange (714) is substantially planar, while the mold cavities (702 - 712) are formed as depressions relative to the plane of the flange (714).

[0132] FIG. 26 also provides a side elevational view of the mold (700) shown in an inverted orientation. In this inverted position, the mold cavities (702 - 712) appear as protuberances rather than depressions, relative to the plane of the flange (714).

[0133] Each mold cavity (702 - 712) is dimensioned to receive a predetermined quantity of a transdermal composition, specifically a mucoadhesive formulation, ensuring precise dosing in the production of mucoadhesive films.

[0134] Each mold cavity (702 - 712) is designed to accommodate a volume of composition corresponding to a single mucoadhesive film unit. A film unit may be utilized as a single-dose administration by a patient. Alternatively, a film unit may comprise multiple doses, requiring subsequent post-processing operations such as cutting the dried film into discrete doses. In such instances, the dried film must be removed from the mold cavity (702 - 712), segmented into desired dosage portions, and optionally packaged. To enhance manufacturing efficiency, the mold (700) is preferably designed such that each mold cavity (702 - 712) forms an individual dosage unit, thereby allowing the mold (700) to function as an integral part of the packaging system.

[0135] In one exemplary embodiment, upon completion of the drying phase, the mold (700) containing the cast film units is removed from the build platform (2). A peelable sheet (not shown) is subsequently applied over the upper surface of the mold (700), adhering releasably to the flange (714) and sealing the film units within the mold cavities (702 - 712). This packaging approach ensures that each film unit remains protected on all sides until use. To access a film unit, the peelable sheet is lifted from an edge, exposing the film for removal from the mold cavity (702 - 712). The mold (700) may be constructed from a flexible material, enabling deformation to facilitate the removal of the film unit from the mold cavity. In such an embodiment, the mold (700) is intended to be a single-use, disposable component, discarded after the film unit is extracted.

[0136] In a particular implementation, the mold (700) is fabricated from a plastic sheet, which is preferably transparent or translucent. The sheet undergoes thermoforming to create the depressions that constitute the mold cavities (702 - 712). The selection of a plastic material with a non-stick surface is preferred to facilitate the release of the dried film when retrieval is required. The transparency or translucency of the mold material offers the advantage of visual inspection, allowing users to view the film's characteristics — such as color, shape, or other identifying features — through the back of the package without opening it. This visibility provides information regarding the film's medicinal properties, active ingredients, dosage strength, expiry date, or intended use, to the extent there is a signal built into the film to communicate a desired property, such as color, pattern, indicia, etc.

[0137] The depth of each mold cavity (702 - 712), represented as dimension (716) in FIG. 26, is selected based on the desired thickness of the dried film unit, ensuring consistency in dosage form. In one implementation, the mucoadhesive composition is dispensed into each mold cavity (702 - 712) to a level substantially flush with the flange (714). As a result, when the film dries, its top surface aligns with the flange (714), allowing the peelable layer to establish direct contact with the film surface, thereby minimizing or eliminating headspace. Reducing headspace is beneficial for maintaining the stability and integrity of the film unit over time.

[0138] In cases where the mucoadhesive composition exhibits shrinkage during the drying process, the volume of composition dispensed into each mold cavity (702 - 712) may be adjusted to exceed the plane of the flange (714) initially. Given the inherent viscosity of the composition, overflow beyond the mold cavity onto the flange (714) is generally avoided. The excess volume is determined based on a shrink factor, representing the ratio between the initial composition volume and the final volume of the dried film. For example, if the shrink factor is 10%, an additional 10% volume of composition is dispensed into each mold cavity to ensure that, upon drying, the film surface remains flush or slightly recessed below the flange (714). This configuration allows the peelable layer to properly adhere and seal the film units. Conversely, it is preferred to prevent a scenario where the dried film surface protrudes above the flange (714), as such protrusions could interfere with the effective sealing of the peelable layer and compromise the integrity of the packaging.

[0139] As previously indicated, the viscosity of the film-forming composition is comparatively high. The composition discharged from the dispensing head (3) into the mold cavities (702 -712) exhibits a viscosity of at least 40,000 centipoise (cPs), advantageously at least 50,000 cPs, further advantageously at least 80,000 cPs, further advantageously at least 100,000 cPs, further advantageously at least 200,000 cPs, further advantageously at least 300,000 cPs,further advantageously at least 400,000 cPs, and further advantageously at least 500,000 cPs. The selection of viscosity within this range is dependent on the specific processing parameters and application requirements.

[0140] Higher viscosity compositions tend to exhibit accelerated drying characteristics, thereby reducing overall drying time. However, excessively high viscosity compositions may present challenges in achieving uniform distribution within the mold cavities, as they do not flow as readily as lower viscosity formulations. A person skilled in the art will determine the appropriate viscosity level by considering machine settings, deposition parameters, and the desired properties of the final film product.

[0141] For compositions of higher viscosity, where the composition deposited at a single location within a mold cavity does not sufficiently spread under gravitational influence to form a uniform layer, a controlled deposition pattern is implemented. Rather than discharging the composition at a single stationary site within the mold cavity, the deposition process is carried out at multiple locations within the cavity. Preferably, this is achieved by generating relative movement between the discharge nozzle of the cartridge mounted on the dispensing head (3) and the mold cavity, ensuring more uniform distribution of the composition within the cavity.

[0142] The deposition pattern may vary based on the mold geometry and viscosity of the composition. Several exemplary deposition patterns are described as follows:

[0143] Perimeter-First Deposition Pattern (FIG. 27): In this pattern, the deposition initiates at a starting position (804), located at a predefined location such as the lower right corner of the mold cavity perimeter (800). The discharge nozzle follows a predetermined travel path (802) along the periphery of the mold cavity, ensuring that the composition is first deposited adjacent to the mold boundary, but inside the boundary. The nozzle then moves towards the center of the cavity, filling the interior while maintaining a uniform layer. This method ensures that the composition remains contained within the mold boundary, preventing unintended overflow. This method can be advantageous in achieving a more consistent layer thickness across the cavity, particularly for compositions with minimal self-leveling properties.

[0144] Center-Outward Deposition Pattern (FIG. 28): In this alternative approach, the deposition begins at a central location (804) of the mold cavity and expands outward towards the periphery. The discharge nozzle follows a travel path (802) that progressively distributes the composition from the center to the mold boundary.

[0145] Cross-Movement Deposition Pattern (FIG. 29): In this deposition strategy, the mold cavity is filled in a widthwise direction using a series of cross-movements (902), while thenozzle progressively advances lengthwise from a predefined starting point (904). This pattern ensures that the entire cavity is systematically covered with a controlled and even distribution of the composition.

[0146] Zig-Zag Deposition Pattern (FIG. 30): In another variation, a zig-zag pattern (1000) is utilized to distribute the composition within the mold cavity. The deposition process begins at a starting position (1004), and the nozzle follows a back-and-forth travel path that spans the cavity. This technique is particularly effective for ensuring uniform coverage in elongated mold cavities and for minimizing inconsistencies in film thickness.

[0147] Each of these deposition patterns is designed to optimize the distribution of high-viscosity compositions within mold cavities, ensuring uniform film formation while mitigating issues related to non-uniform flow behavior. The selection of an appropriate deposition pattern is dependent on factors such as mold cavity dimensions, composition viscosity, and machine dispensing capabilities.

[0148] FIG. 31 presents a detailed flowchart illustrating the process for manufacturing a mucoadhesive film. This flowchart is structurally similar to the flowchart in FIG. 8A; however, it provides additional details regarding specific process steps not explicitly depicted in FIG.8A. For consistency, process steps that are common to both flowcharts are designated with the same reference numerals, though their descriptions are not repeated herein.

[0149] A newly introduced step, designated as step (1100), involves the input of user-defined parameters specifying the characteristics of the mucoadhesive film to be produced. This parameter entry is facilitated via a graphical user interface (GUI). Referring back to FIG. 7, the user initiates this process by selecting the “mucoadhesive film” option from the GUI menu, which in turn leads to additional GUI sub-options (not shown).

[0150] At least one GUI control is implemented to allow the user to define critical film characteristics. Such characteristics may include, but are not limited to, the number of film units to be produced, the desired film unit size, the target film thickness, and other relevant physical attributes. The GUI control presents these selectable options in a structured format, enabling the user to make selections from predefined parameters, thereby ensuring consistency and repeatability in film production.

[0151] Furthermore, an additional GUI control is provided for defining the attributes of the mold to be used in the dispensing process. Among the mold parameters that may be specified are the number of mold cavities to be filled and the spatial configuration of the mold cavities. The spatial configuration determines the exact positioning of each mold cavity, allowing theprocessing unit of device (10) to accurately reference each cavity relative to the dispensing head. This ensures precise deposition of the composition into the designated mold cavities.

[0152] In an exemplary implementation, the GUI control is designed to present a visual representation of a range of permissible mold cavity configurations. These configurations may vary in terms of the number of cavities, their spatial arrangement, and their overall distribution within the mold. The user can navigate through various mold configuration options and select the one corresponding to their intended application. Each selectable mold configuration is associated with a stored dimensional profile, maintained in the memory of the processing unit.

[0153] A stored dimensional profile encompasses spatial data, including but not limited to:The total number of mold cavitiesThe arrangement of mold cavities within the mold (e.g., number of rows and columns for rectangular configurations)The dimensions of individual mold cavitiesThe positional relationship of each mold cavity relative to a predefined reference point

[0154] Additionally, this GUI control may offer a further selection mechanism allowing the user to specify the composition deposition pattern. This selection mechanism is designed using a structured options system, where the user selects from predefined deposition patterns, ensuring optimized material distribution within the mold cavities.

[0155] Once the user-defined inputs are finalized in step (1100), the process advances to step (1102). Prior to executing step (1102), the selected physical mold must be correctly positioned on the build platform (2). To ensure precise alignment, a fixture mechanism is preferably employed, allowing the mold to be secured at a known reference position. This reference position serves as a basis for calculating positional offsets when the build platform is displaced along the X-Y axes during operation. The fixture mechanism may include complementary mating components — one on the mold and another on the build platform — that engage upon placement of the mold onto the build platform, ensuring reliable positioning and alignment.

[0156] At step (1102), the dispensing head (3) is activated to dispense the mucoadhesive composition into each mold cavity in accordance with the preselected deposition pattern. Upon completion of the filling process, the system transitions to step (52), where the heating function is executed to facilitate drying of the deposited film composition. This controlled heating stepensures that the film material reaches the required state for subsequent handling, packaging, or further processing.

[0157] The detailed flowchart in FIG. 31 thus provides an expanded and systematic representation of the mucoadhesive film manufacturing process, enhancing precision in both user control and operational execution.

[0158] Referring now to FIG. 8B, a flowchart illustrates an alternative process performed by the device (10), which corresponds to a distinct operational function identified as “Dispense Ingredient”. For clarity and brevity, steps 32 through 40 in this process are identical to the steps described in the flowchart of FIG. 8A, and the detailed description of these steps will not be repeated here.

[0159] The process diverges at step 54, where a sub-menu specific to the “Dispense Ingredient” function is displayed via the graphical user interface (GUI). While this sub-menu is not explicitly illustrated in the accompanying drawings, it is understood that the sub-menu facilitates user input for a variety of parameters relevant to the dispensing of ingredients. These parameters are configured to tailor the dispensing operation to the user’s specific requirements.

[0160] At step 56, the user specifies the ingredient to be dispensed. This may be accomplished in several ways, depending on the implementation of the device (10). One such method involves the user inputting an ingredient identifier, which uniquely identifies the desired ingredient. To enhance user convenience, the GUI may also present a dynamically generated list of selectable ingredients. This list is automatically updated based on the cartridges (7) loaded in the dispensing head (3) at any given time.

[0161] In particular, when the cartridges (7) containing various ingredients are swapped or replaced in the dispensing head (3), the device (10) dynamically updates the list displayed on the GUI. This ensures that the displayed options accurately represent the ingredients currently available for dispensing. The dynamic list functionality minimizes user error by preventing the selection of unavailable ingredients and aligns the dispensing operation with the physical configuration of the device (10).

[0162] As an alternative to selecting from the dynamically updated list, the user may specify the ingredient to be dispensed by referencing the slot number associated with a particular cartridge in the dispensing head (3). This alternative selection method allows the user to bypass the need for ingredient identifiers or dynamic lists.

[0163] It should be noted that the dispensing head (3) of the device (10) is capable of dispensing more than one ingredient. When multiple ingredients are selected for dispensing, the dispensing operation can be carried out either in a sequential manner or concurrently. The determination of whether the dispensing operation is performed sequentially or concurrently depends on several factors, including the geometry and configuration of the device (10), as well as the geometry and configuration of the container into which the ingredients are to be dispensed.

[0164] Specifically, if the geometry of the container is sufficiently large to accommodate the simultaneous delivery of multiple ingredients and if the distance between the dispensing nozzles of the cartridges (7) in the dispensing head (3) is minimal enough to allow for accurate deposition within the container, concurrent dispensing is feasible. In this scenario, the ingredients can be dispensed simultaneously, enabling faster preparation of multi-component compositions.

[0165] Conversely, if the container geometry is constrained, such that simultaneous dispensing from multiple nozzles would result in imprecise ingredient placement, or if the distance between the dispensing nozzles of the cartridges (7) is too large to ensure proper alignment with the designated dispensing area, sequential dispensing is preferred. In sequential dispensing, each ingredient is dispensed one at a time, in a predetermined order, to prevent misalignment.

[0166] The device (10) may be configured to automatically determine whether concurrent or sequential dispensing is appropriate based on sensor feedback or user-input parameters. For example, the device (10) can analyze the dimensions and configuration of the container using sensors or preloaded specifications and select the appropriate dispensing mode accordingly. Alternatively, the user may manually select the dispensing mode via the graphical user interface (GUI) based on their specific requirements.

[0167] At step 58, the user provides input regarding the quantity of the ingredient to be dispensed. This quantity may be expressed in various units, such as weight, volume, or any other units deemed appropriate for the specific application. The flexibility in defining the dispensing quantity allows the device (10) to accommodate a wide range of user requirements and applications.

[0168] At step 60, the user specifies the parameters of the container to be used for receiving the dispensed ingredient(s). This step is performed via the graphical user interface (GUI), where the user can select a container from a predefined set of options presented by the device(10). These options may correspond to containers of varying dimensions, shapes, and materials, ensuring compatibility with different dispensing scenarios. The container options can be dynamically updated based on the current configuration of the device (10) or specific cartridges (7) loaded in the dispensing head (3).

[0169] At step 62, the dispensing operation is performed. Before activating the dispensing head (3), the build platform (2) is repositioned relative to the dispensing head (3) to provide the necessary clearance for the container. This repositioning ensures that the container is accurately aligned with the dispensing head (3), preventing spillage or misalignment during the dispensing operation. The container can be placed on the build platform (2) either manually by the user or automatically retrieved from a container magazine integrated into the device (10).

[0170] Once the container is correctly positioned beneath the dispensing head (3), the dispensing operation is initiated. The dispensing mechanism operates based on the specified quantity of the ingredient(s). If the amount to be dispensed is defined by weight, the device (10) monitors the output of the precision weighing sensor integrated into the build platform (2). This sensor continuously monitors the weight of the container as the ingredient(s) are dispensed. The dispensing operation ceases automatically when the measured weight reaches the target value.

[0171] Alternatively, if the dispensing operation is managed based on volume, the device (10) utilizes a flow meter integrated into the dispensing system. This flow meter measures the flow rate of the dispensed ingredient(s) in real-time. The device (10) terminates the dispensing operation once the flow meter detects that the specified volume has been reached.

[0172] After completion of the ingredient dispensing operation, the material needs to be homogenized to substantially uniformly distribute the active ingredient throughout the excipient, carrier or diluent. This can be accomplished by mixing the material using a mixer. One example of a mixer, which workswell is a bladeless planetary mixer of the type described in the International Patent Application of Medisca Pharmaceutique WO2018085942, the contents of which are hereby incorporated by reference.

[0173] Referring now to FIG. 9, a high-level schematic representation of the bladeless planetary mixer is illustrated, designated generally by the reference numeral 130. The planetary mixer (130) is configured for efficient and thorough mixing of ingredients placed within a container. The planetary mixer comprises a casing, within which is operably mounteda rotor (132). Attached to the rotor (132) is a basket (131 j), designed to securely house the container containing the ingredients to be mixed.

[0174] During operation, the basket (131j) is subjected to superimposed revolution and rotational movements, a characteristic feature of planetary mixers that enhances the homogeneity of the mixing process. Specifically, as the rotor (132) rotates, depicted in the figure with a clockwise rotational arrow (it being understood that counterclockwise rotation is equally feasible), the basket (131 j) is simultaneously subjected to a revolutionary movement about a substantially vertical axis, designated as Z2. Concurrently, the basket (131j) undergoes a rotational movement about a secondary axis, designated as Z1 , which is oriented at an angle relative to the vertical axis Z2. This superimposed motion, comprising simultaneous revolution and rotation, creates a highly effective mixing dynamic by subjecting the container and its contents to complex, multidirectional forces.

[0175] The basket (131 j) is further equipped with an internal structure specifically designed to support and stabilize the container during operation. This structure includes lugs (135i) and (135k), which engage with an adapter configured to securely hold the container. The lugs (135i, 135k) are positioned to establish a positive engagement with the adapter, ensuring that the adapter and the container housed within remain fixed relative to the basket (131j) during operation. This engagement prevents undesired movement or displacement of the adapter and container, thereby maintaining stability and ensuring consistent mixing performance.

[0176] Examples of containers and adapters which can be used with the device (10) and the bladeless planetary mixer 130 are shown at FIG.s 10 to 15.

[0177] The container 202 in FIG. 10 has a generally cylindrical body 222 with threads 240 at the top configured to engage with a cover 203. The cover has a periphery 238 with serrations 227 to increase grip. The cover 203 has a top surface 223 including a projection, which is centrally located and has an aperture, defining a nozzle. The aperture extends along an imaginary axis 233. The projection is threaded and can threadedly engage with a cap, having a domed configuration to close the nozzle. Optionally, not shown in the drawings, the container 202 can have a moveable bottom wall, operating as a piston to allow material in the container to be expelled from the nozzle, when the bottom piston wall is pushed upwardly.

[0178] The container 202 is suitable for use with the device (10) to receive ingredient(s) discharged from the dispensing head 3. To receive ingredients, the cover 203 is removed and the container body 222 is placed on the build platform 2, as previously indicated. Optionally, the build platform 2 can be provided with a fixture to hold the container body 222 on the buildplatform 2 and to positively locate it at a predetermined reference position in the device (10), such that the container body 222 can be accurately registered in relation to the dispensing head 3.

[0179] In one possible application, the container body 222 is pre-filled with a first ingredient, and a second ingredient is deposited on top of the first ingredient by the dispensing head 3. The first ingredient can be an excipient, diluent or carrier in which the second ingredient, such as an API, can be dispersed to form the final pharmaceutical preparation. In a second possible application, the container body 222 is empty and it is placed as such on the build platform 2. The dispensing head 3 thus discharges at least one ingredient in the empty container body 222. When the dispensing operation is completed, the container body is removed for performing post- processing steps, which may include placing an additional ingredient in the container, which can be an excipient, diluent or carrier. In a third possible application, several ingredients are dispensed in the container body from the dispensing head 3. The ingredients can be dispensed simultaneously or sequentially. For instance, a first active ingredient can be dispensed from one cartridge 7, while a second active ingredient can be dispensed from a second cartridge 7 and a third ingredient is dispensed from a third cartridge 7, which can be an excipient, diluent or carrier. The container body which now holds three ingredients, is ready for post-processing steps, including receiving additional ingredients, mixing, etc.

[0180] In these tree examples, the container body is filled with several ingredients, however, those ingredients are not mixed to provide a homogenized composition that can be used to provide a therapeutic effect. To mix the ingredients, a bladeless planetary mixer can be used, where the mixing operation can be performed directly in the container 202. Specifically, the container body 222 is closed using the cover 203 and the cap is screwed on the nozzle. The closed container 202 is placed in the bladeless planetary mixer, such as the one shown in FIG. 9, and the mixing cycle can be performed to homogenize the ingredients. Since the container 202 is most likely of different dimensions than the basket of the bladeless planetary mixer, an adapter is used to properly fit the container 202 in the basket. An example of adapter is shown at FIG.s 11 , and 12.

[0181] The adapter 204 is configured to securely grip the container 202 such that the container 202 is stable and does not move during the mixing operation. To maintain balance, the adapter locates the container relative to the basket such that the longitudinal axis of the container, which coincides with the axis of the nozzle 233 is co-axial with the rotation axis of the basket Z1. The adapter has two mating shells 225I and 225h that cradle the container 202 to form an internal cavity in which the container 202 securely fits. The adapter 204 has recesses 205a which matingly engage with lugs 135i and 135k to lock the adapter 204 withthe container 202 therein against rotation in the basket. FIG. 12 the container / adapter assembly 200 which is ready for placement in the basket of the planetary mixer is shown at FIG. 12.

[0182] FIG. 13 shows another example of a container which can be used for receiving ingredients dispensed from the dispensing head 3. The container 102 is referred to as a dispensing container since it includes a metering mechanism allowing to dispense metered doses of the composition. A metered dose corresponds to a predetermined amount / volume of material. The metering mechanism can be designed to dispense a range of different doses. The metering mechanism is actuated by the user and in response to each actuation, releases through a nozzle a metered dose.

[0183] The dispensing container shown in FIG. 13 uses a metering mechanism which is based on a pump design. When the user presses on the actuator (not shown), the metering mechanism expresses a metered dose. The dispensing container 102 has a longitudinal axis 133 and comprises a container body 122, which is closed at its top end via closure 123. The closure 123 may interface with the container body 122 via threads or via a one-way snap fit arrangement, to prevent the container 102 from being opened once the closure 123 is put on place on the container body 122. This makes the container 102 a single use container, since the closure 123 is locked in place and cannot be removed once it is installed.

[0184] While not shown in the drawings, the metering mechanism is located on the closure 123, and it is designed to pump out the composition from the container body 122, in response to operation of the actuator of the metering mechanism. Note that the bottom wall of the container body 122 is moveable within the container body, as the composition is pumped out. A removable cylindrical cap is placed on the closure to protect the metering mechanism and also to provide the container 102 with a more pleasant visual appearance.

[0185] A corresponding adapter allowing to use the container in the bladeless planetary mixer is shown at FIG. 14. The adapter 101 is also designed as a mating shell structure which engages with the lugs 135i and 135k of the basket.

[0186] In order to use the container 102 in the device (10), the closure 123 is removed to expose the open top of the container body 122, which optionally can be pre-filled with an ingredient, and then the container body 122 is placed on the build platform 2 and secured therein with the optional fixture. Once the dispensing operation via the dispensing head 3 is completed, the container body 122 is removed from the device (10), any additional ingredients added in the container body 122, the closure 123 is locked in place and the container 102 isplaced in the bladeless planetary mixer to mix the ingredients, using an adapter, if required. After the mixing is completed, the container 102 is ready for use and can be provided as such to the patient / user for the therapeutic treatment.

[0187] FIG. 15 illustrates yet another embodiment of a dispensing container 2502 which can also be used in the device (10) and then in the bladeless planetary mixer. The dispensing container 2502 has a longitudinal axis 1533m also uses a metering mechanism to dispense metered doses of the composition in the container body, but this metering mechanism, of a type known in the art, uses a piston which is positively displaced to express the composition from a nozzle, in metered amounts. For instance, the dispensing container 2502 has a lower rotating ring, which forms a base of the container 2502, and which, when subjected to an angular displacement, causes axial movement of the piston in the cavity of the container body to express the composition through a nozzle in the upper part of the container 2502. A ratchet mechanism can be provided to control the angular movement in discrete steps, where each step corresponds to a metered amount. The container 2502 has a closure which is also of the one-way lock type to make the container 2502 a single use container.

[0188] The container 2502 is used in a similar fashion with the device (10) as discussed in relation to container 102 and the description will not be repeated. After the container 2502 is filled, it is placed in the bladeless planetary mixer, optionally with an adapter, which is shown partially at FIG. 15. The adapter is of similar design as the adapters, previously described, and varies only by its geometrical configuration to adapt to the structural features of the container 2502. Each mating half of the adapter has semi-circular segments 2515 configured to grip corresponding portions of the side wall of the container 2502. The mating halves are engaged to each other via tongue and groove arrangements 2509i and 2508L Recesses 2505i are configured to mate with the lugs 135i, 135k.

[0189] FIG. 20 is flowchart which illustrates the steps of the process for using anyone of the containers in FIG.s 10, 13 and 15, with the device (10) and then in a planetary mixer to mix ingredients dispensed by the device (10). At step 300, the container is opened. At the optional step 302, an ingredient is placed in the container, which can be an excipient, diluent or carrier. At step 304, the container is placed on the build platform and at step 306 the device (10) is programmed as discussed previously to specify an amount of an ingredient to be dispensed. Optionally, the programming step includes specifying an ingredient, selected among a list of possible ingredients that the device (10) is capable of dispensing. At step 308, the dispensing head 3 is actuated to dispense the pre-set amount of the ingredient. In the case when several ingredients are to be dispensed, step 308 is repeated accordingly. The container is removed from the device (10), optionally additional ingredients are placed in the container and at step310, the container is closed. The closure can be a one-way lock in type, such that it cannot be removed, for containers which include a metering mechanism. If required, the container is placed in an adapter, as shown by the optional step 312, and the adapter / container assembly is placed in a bladeless planetary mixer at step 314. At step 316, the container is subjected to superimposed rotation and revolution movements. And, at step 318 the container, which is now ready to use can be provided to a patient for therapeutic treatment.

[0190] FIG. 16 is a schematical illustration of an ingredient cartridge 7, showing the main components of the cartridge 7. The cartridge 7 includes a material container 320 having a determined volume to hold a quantity of material therein. A metering mechanism 322 is provided which is in fluid communication with the material container 320 to discharge from the cartridge 7 controlled amounts of material. The metering mechanism can be based on a continuous flow principle, where once the metering mechanism is actuated, it discharges a continuous flow of material from the cartridge. The flow of material from the cartridge 7 can be produced at a predetermined flow rate, consequently the total volume of material discharged from the cartridge 7 depends on the amount of time the metering mechanism is actuated. Alternatively, the metering mechanism 322 can be configured to provide a variable flow rate discharge. In a specific example of implementation, the metering mechanism includes a valve having at least two operative states, namely an opened state and a closed state. When a pressure differential is created in the cartridge 7 and when the valve is set in the opened state, the material flows through the valve. The flow rate of material out of the cartridge is determined by several factors, such as the pressure differential between the inside of the material container 320 and the outside, the flow rate characteristics of the valve and other components of the fluid discharge pathway of the metering mechanism 322.

[0191] In a variant, the metering mechanism 322 includes a positive displacement arrangement, which is configured to eject a predetermined amount of material, during an ejection cycle. The total amount of material discharged from the cartridge 7 is determined by controlling the number of ejection cycles, where each cycle discharges a predetermined amount of material.

[0192] The material container 320 is in fluid communication with the metering mechanism 322, such as to maintain a continuous supply of material to the positive displacement arrangement. In the example shown in FIG. 16, the material container 320 sits atop the metering mechanism 322 such that the material flows from the material container 320 to the metering mechanism 322 by gravity. Alternatively, positive pressure can be established inside the material container 320 such as to cause the material to migrate under a pressure differential from the material container 320 to the metering mechanism 322. In thisarrangement, it is not necessary to configure the cartridge 7 to create a gravity flow from the material container 7 to the metering mechanism and the material container 320 can be located in a different position relative to the metering mechanism 322. In a possible variant, the positive displacement arrangement can be configured to create suction such as to suck the material out of the material container 320 and deliver it to the metering mechanism 322.

[0193] In the example shown in FIG. 16, the cartridge 7 is configured as a unit, where the metering mechanism 322 is physically connected to the material container 320. In this form of implementation, the cartridge 7 can be of disposable design. Once the cartridge 7 is empty, it can be thrown away of or recycled. When the cartridge 7 is disposable, the material container 320 is sealed and it is not intended for the user to open the material container 320, such as to be able to refill it, for example. In this example, the material container 320 has a top portion which is closed permanently by a cover (not shown). During manufacture, the top of the material container 320 is left open to allow the material to be deposited in the material container 320 and when the filling operation is completed, the cover is put in place and the top of the material container 320 is sealed, mechanically, with an adhesive, ultrasonic welding, or other.

[0194] If desired to allow the cartridge 7 to be refillable, the cover is designed to be removable. As such, the cover can be a screw cover, which is removed by the user when the material container 320 is depleted, to be refilled.

[0195] In use, the cartridge 7 is loaded in an empty cartridge slot in the dispensing head 3. A cooperating mechanical arrangement locks the cartridge 7 in the slot such that the cartridge 7 is securely held in place. Electrical contacts in the slot mate and engage corresponding electrical contacts on the cartridge 7, such that the metering mechanism 322 can be electrically operated and controlled. When the cartridge 7 is depleted, it is pulled out from the dispensing head, discarded or refilled, and a new cartridge 7 or a refilled one is installed in the dispensing head 3.

[0196] FIG. 17 shows an alternative arrangement of a cartridge 7, where the material container 324 is mounted remotely from the metering mechanism 322. In this arrangement, the material container 324 is in fluid communication via a conduit 326 allowing material to flow from the material container 7 to the metering mechanism 322. The conduit 326 can be a flexible tubing of the desired length. The material in the material container 7 can be delivered to the metering mechanism 322 by establishing positive pressure in the material container 324. In this arrangement, the cartridge 7 is no longer of a unitary structure design, rather it has a modular configuration, made up of different modules or elements, allowing mountingthe material cartridge 324 outside of the dispensing head 3, such that if the dispensing head 3 is moved in the X-Y plane during the deposition of the ingredient(s) on the build platform, only the metering mechanism 322 is displaced with the dispensing head 3, while the material container 324 is held stationary but in fluid communication with the metering mechanism 322 via the flexible tubing 326. When the cartridge 7 is empty, it may not be necessary to remove the metering mechanism 322 from the dispensing head 3 and suffices to disconnect the flexible tubing from the metering mechanism 322 and reconnect the flexible tubing of a new material container 324 or one that has been refilled. It is also possible to provide the material container 324 with a re-closable cover (not shown) allowing re-filling the material container 324 while the ingredient container 324 is mounted in the device (10).

[0197] The material in the material container 320, 324 is a liquid, which has a viscosity in a range of viscosities. In one example, the liquid material can be free-flowing and in another example, the liquid material can still be able to flow under gravity but more slowly than when free flowing. The choice of viscosity is determined based on the intended application. For one particular dosage form, such as a mucoadhesive film, a heavier viscosity is used resulting from the choice of materials necessary to make up the mucoadhesive film precursor, and also the material casting dynamic. For a different dosage form, such as when delivering an ingredient to an excipient, diluent or carrier a free-flowing material can be used, since the delivered ingredient will be mixed as a post processing operation with the excipient, diluent or carrier.

[0198] The material in the cartridge 7 includes an ingredient which is used during the preparation of the pharmaceutical composition. The ingredient can be an active ingredient, such as an API, an excipient, diluent or carrier, or a combination of both, among other possibilities. Typically, APIs are manufactured and distributed in powder form and to be able to be dispensed by the cartridge 7, the API is put in a solution or suspension, which is then placed in the cartridge 7 for metered dispensing. In that example, the metering mechanism 322 dispenses the API in solution / suspension. The total amount of API dispensed, is determined by the total volume of material dispensed and also the concentration of the API in the solution / suspension. It is thus important that the concentration of the API in the solution / suspension is substantially uniform and free of entrapped air. A non-uniform API distribution will create a variability in the amount of API which is delivered, as certain strata of the body of material in the container 320 / 324 will have a higher concentration than other strata. Also, during transport or manipulation of the cartridge 7, it is possible that the cartridge 7 is agitated to cause air entrapment, which also causes variability of the distribution of the API.

[0199] Accordingly, a process of delivering an ingredient via the device (10) using the cartridge 7 includes the step of homogenizing and / or deaerating the material in the cartridge 7 by subjecting the cartridge 7 to superimposed revolution and rotation movements in a bladeless planetary mixer.

[0200] In one example, prior to using the cartridge for the dispensing of an ingredient, the material in the cartridge 7 is processed in the bladeless planetary mixer. One option is to remove the material from the cartridge, process it in the planetary mixer to homogenize and / or deaerate the material, and then put the homogenized and deaerated material back in the cartridge 7, which is ready for use. In a more practical approach, which avoid the need to remove the material from the cartridge 7, the entire cartridge 7, or a component of the cartridge holding the material is processed placed in the planetary mixer to be subjected to superimposed revolution / rotation movements.

[0201] In accordance with the present disclosure, the cartridge (7) is preferably supported within the basket of the planetary mixer through the use of an adapter. The adapter is configured to include an internal cavity dimensioned and shaped to receive and securely retain the cartridge (7). The internal cavity is precisely contoured to conform to the external geometry of the cartridge (7), thereby ensuring a secure fit that minimizes or eliminates vibrations during the operation of the planetary mixer. Such a configuration enhances stability and ensures optimal mixing performance.

[0202] In one exemplary embodiment, the adapter is of a clam-shell design, as depicted in FIG. 15, wherein the adapter comprises two complementary mating halves that define an internal cavity when closed. In an open configuration, the mating halves expose the cavity, facilitating the insertion of the cartridge (7). Once the cartridge (7) is positioned within the cavity, the adapter is closed, effectively encapsulating the cartridge. Subsequently, the adapter, containing the cartridge (7), is placed into the basket of the planetary mixer, thereby enabling the mixing operation to commence.

[0203] In certain implementations, the cartridge (7) is designed as an integrated unit wherein the material container (320) and the metering mechanism (322) form a unitary structure. In such configurations, both the material container (320) and the metering mechanism (322) are positioned within the adapter and subjected to the superimposed revolution and rotation movements characteristic of the planetary mixer. The cartridge (7) preferably adopts a generally cylindrical geometry, which facilitates ease of accommodation within the adapter while optimizing the volumetric capacity of the material container (320) relative to the adapter size.

[0204] In this particular embodiment, the material container (320) exhibits a generally cylindrical profile that is received within a correspondingly cylindrical portion of the adapter’s cavity. The metering mechanism (322) is positioned subjacent to the cylindrical material container (320) and is likewise enclosed within the adapter. Consequently, in this arrangement, during the mixing operation, the material container (320) is disposed above the metering mechanism (322).

[0205] In an alternative embodiment, the orientation of the cartridge (7) within the adapter may be reversed relative to its standard operating position. Specifically, the cartridge (7) may be supported in an inverted orientation compared to its typical use position, i.e., the position in which it is installed within the dispensing head (3). In this configuration, the metering mechanism (322) is disposed above the material container (320) and may extend beyond the confines of the adapter. This embodiment corresponds to the arrangement illustrated in FIG.12, wherein the adapter is provided with an aperture at the upper region to accommodate a protrusion extending from the container body below.

[0206] In applications wherein the cartridge (7) is of a modular design, such as the arrangement illustrated in FIG. 17, it is not required to position the entire cartridge within the adapter. Specifically, the metering mechanism (322) does not need to be placed within the adapter, thereby allowing only the material container (324) to be inserted into the adapter for the purpose of mixing the ingredients contained therein. In such a configuration, the port to which the conduit (326) is connected must be closed during the mixing operation to prevent any unintended spillage of the ingredients into the planetary mixer. This closure mechanism prevents contamination or loss of material.

[0207] The material container (324) is preferably configured with a cylindrical geometry, consistent with the previously described advantages of volumetric efficiency in relation to the adapter’s dimensional constraints. This design facilitates seamless integration into the adapter while maximizing the internal volume available for ingredient containment. Furthermore, the cylindrical configuration contributes to the uniform distribution of rotational forces exerted during mixing, thereby enhancing the homogeneity of the mixture.

[0208] Referring now to FIG. 21 , a flowchart is provided that illustrates the steps of a method for preparing a cartridge containing multiple ingredients for use with a dispensing apparatus (10). The process ensures proper mixing, homogenization, and de-aeration of the ingredients contained within the cartridge to maintain formulation integrity and dispensing accuracy.

[0209] At step 400, a cartridge, such as cartridge (7), which comprises a material container (320) and an associated metering mechanism (322), is optionally positioned within an adapter. If an adapter is not utilized, the cartridge (7) is directly compatible with the planetary mixer's basket, thereby enabling direct placement without requiring additional interfacing components. The material container (320) of the cartridge is pre-filled with multiple ingredients. For example, the ingredients may include an active pharmaceutical ingredient (API) suspended or dissolved in an excipient, diluent, or carrier. In certain embodiments, the material container (320) is hermetically sealed at the point of manufacture, thereby preventing user access to its contents and preserving formulation stability during storage and transportation.

[0210] Once filled at the manufacturing facility, the ingredients within the material container (320) are typically mixed to ensure a uniform distribution of the API within the excipient, carrier, or diluent. However, prolonged storage may result in phase separation, wherein the API may settle into a concentrated lower stratum. Additionally, during transit, mechanical agitation may induce aeration, leading to the formation of air bubbles within the formulation. To mitigate these issues, it is necessary to re-homogenize the contents of the material container (320) prior to use, thereby restoring uniform API distribution and facilitating the removal of entrapped air.

[0211] In alternative embodiments, the material container (320) may be configured to allow user access for the introduction of additional ingredients. As described herein, the cartridge may be preloaded at the manufacturing facility with a first ingredient, such as an API in powdered form, while remaining accessible for user-driven additions. In such embodiments, the material container (320) is sealed with a re-openable closure, allowing the user to introduce a secondary ingredient (e.g., a carrier, excipient, or diluent) immediately priorto use. In this state, the contents of the material container (320) remain unmixed until subjected to a mixing cycle.

[0212] At step 402, the cartridge (7) containing the ingredients, whether pre-mixed or unmixed, is placed into the planetary mixer. This placement may be facilitated either by directly inserting the cartridge (7) into the planetary mixer’s basket (wherein the cartridge is dimensioned to fit securely within the basket) or by employing an adapter, as previously described.

[0213] At step 404, the mixing cycle is initiated. The mixing parameters, including duration and speed, may be adjusted in accordance with the specific characteristics of the formulation. These parameters may be optimized based on factors such as ingredient composition, viscosity, volume of the material container (320), and the required degree of homogenization.

[0214] At step 406, upon completion of the mixing cycle, the adapter (if used) is removed from the planetary mixer. At step 408, the cartridge (7) is removed from the adapter. In cases where no adapter was used, the cartridge (7) is directly removed from the planetary mixer’s basket.

[0215] At step 412, the mixed and de-aerated cartridge (7) is installed into the dispensing head (3) of the dispensing apparatus (10), rendering the system operational and ready for use.

[0216] When the cartridge (7) is configured with a modular design, as illustrated in FIG. 17, the process for mixing, re-mixing, and de-aerating the ingredients remains consistent with the previously described methodology. However, an additional preparatory step is required wherein the port to which the conduit (326) connects must be sealed to prevent inadvertent spillage or contamination of the formulation during the mixing operation.

[0217] As previously discussed, the cartridge (7) may be prefilled at the manufacturing facility with a formulation comprising all necessary ingredients in predetermined quantities to achieve a specific active pharmaceutical ingredient (API) concentration. This approach offers a high degree of user convenience, as it eliminates the need for manual ingredient addition, precise weighing, and subsequent mixing by the end user. Consequently, this implementation streamlines the preparation process and reduces the risk of formulation errors. However, premixed API formulations may exhibit a reduced shelf life due to potential degradation over time, and they may necessitate stricter regulatory compliance measures, making prefilled cartridges less suitable for certain applications.

[0218] To provide an alternative approach that balances convenience with flexibility, the cartridge (7) may be pre-loaded with one or more ingredients while permitting the end user to introduce additional ingredients before use. This implementation allows for final preparation and customization of the formulation immediately prior to use, accommodating specific user preferences or regulatory considerations.

[0219] A specific embodiment of this approach is depicted in FIG. 18, wherein the material container (320) is equipped with a resealable closure (500), such as a screw cap, which can be opened to facilitate the introduction of additional ingredients. In this example, the cartridge (7) is pre-loaded at the factory with a predetermined quantity of a first ingredient (502), which is in powdered form. The first ingredient (502) may be an API or another active or non-active component required for the formulation. In this initial state, the cartridge (7) is not yet ready for use, as the formulation remains incomplete.

[0220] To finalize the preparation, the end user opens the closure (500) and introduces a second ingredient into the material container (320). The second ingredient may be an excipient, diluent, or carrier substance, selected based on the required formulation properties. The amount of the second ingredient can be adjusted by the end user, allowing for precise customization of the final concentration of the first ingredient (502). This adjustable approach provides enhanced flexibility, enabling the user to tailor the final formulation to specific therapeutic requirements or application needs.

[0221] Once all the ingredients are combined, the cartridge is placed in the planetary mixer to homogenize and de-aerate the mixture, as discussed previously.

[0222] In an alternative embodiment, as illustrated in FIG. 19, the cartridge (7) is pre-loaded with multiple ingredients; however, these ingredients remain segregated until the cartridge is ready for use. At the time of use, the ingredients are combined and subjected to a mixing process. The material container (320) is specifically engineered to include a plurality of internal compartments, each designated to house a respective ingredient.

[0223] More particularly, the material container (320) comprises a first compartment (504), which is configured to receive a first ingredient (502). The first ingredient (502) may be in powdered form or an alternative state, depending on formulation requirements. Additionally, the material container (320) incorporates a second compartment (506), which is designated to receive a second ingredient (508). The second ingredient (508) is typically in liquid form, but alternative physical states may be utilized depending on the intended application.

[0224] A partition (510) is positioned between the first compartment (504) and the second compartment (506), effectively isolating the first ingredient (502) from the second ingredient (508). The partition (510) is preferably fluid-tight to ensure that if either the first or second ingredient is in liquid form, the partition prevents undesired mixing or leakage into the adjacent compartment. This fluid-tight configuration maintains the stability of the ingredients until intentional mixing is initiated by the user.

[0225] The partition (510) is designed to be removable. The term "removable" as used herein refers to any mechanism by which the function of the partition is negated, permitting the first and second ingredients to mix. The partition (510) may be physically extracted from the material container (320), or alternatively, its structural integrity may be altered to facilitate ingredient mixing, such as by tearing, puncturing, or dissolving the partition material.

[0226] In one exemplary implementation, the partition (510) is fabricated from a rigid plastic material and is generally rectangular in shape. The partition is designed to slide within verticaltracks that are formed along the internal walls of the material container (320). When the partition (510) is fully inserted within the material container (320), as depicted in FIG. 19, the first compartment (504) and second compartment (506) remain hermetically separated, thereby preventing premature interaction between the ingredients.

[0227] To facilitate user operation, the partition (510) is equipped with a pull-tab or an equivalent actuating structure. This pull-tab allows the end user to manually extract the partition (510) by pulling it vertically along the defined tracks. As the partition (510) is removed, the previously segregated compartments (504, 506) are merged, thereby permitting the first ingredient (502) and the second ingredient (508) to mix within the material container (320). This design ensures controlled and precise initiation of the mixing process, enabling the formulation to achieve homogeneity prior to dispensing.

[0228] This modular cartridge configuration provides several advantages, including enhanced ingredient stability during storage, prevention of premature interactions, and user-controlled activation of the mixing process.

[0229] Upon removal of the partition (510), the first compartment (504) and the second compartment (506) are merged, allowing the previously segregated ingredients to come into contact with each other. At this stage, the cartridge (7) is prepared for the mixing process, which is conducted to achieve ingredient homogeneity and to eliminate any entrapped air within the formulation.

[0230] To facilitate this mixing and deaeration process, the cartridge (7) is positioned within a planetary mixer, as previously described. The planetary mixer imparts superimposed rotational and revolutional movements to the cartridge (7), thereby ensuring thorough mixing of the combined ingredients. The mixing parameters, including speed and duration, among others, may be adjusted based on the specific formulation requirements to achieve optimal dispersion and uniformity.

[0231] Following completion of the mixing and deaeration cycle, the cartridge (7) is rendered ready for use. At this stage, the formulation within the material container (320) has achieved the desired level of homogeneity and is free from entrapped air, ensuring consistent dispensing accuracy.

[0232] The prepared cartridge (7) is then loaded into the dispensing head (3) of the dispensing apparatus (10). The cartridge (7) is securely positioned within the dispensing head (3), establishing a functional connection with the control circuitry of the device 10 which operates the metering mechanism (322). Once installed, the dispensing apparatus (10) is fullyoperational, allowing for precise and controlled dispensing of the prepared formulation as required for its intended application.

[0233] In an alternative embodiment, the cartridge (7) may be configured with a metering mechanism that is structurally and functionally distinct from the container (320), thereby forming a modular assembly. In this implementation, the metering mechanism is operatively attachable to the container (320) to establish an integrated yet detachable functional cartridge system. This configuration presents several advantages for various applications.

[0234] One advantage of this modular arrangement is that the metering mechanism may be reutilized across multiple container cycles. Specifically, upon depletion of the fluid or mixture contained within the container (320), the metering mechanism can be detached and affixed to a new, filled container (320), thereby forming an operational cartridge without necessitating the replacement of the entire metering system. This reduces material waste and enhances cost-effectiveness.

[0235] A further advantage of this embodiment is the potential for manufacturing efficiencies. The container (320) and the metering mechanism may be fabricated separately, eliminating the requirement for factory-level assembly of these components into a singular unit. This separation allows for independent quality control measures and facilitates logistical flexibility in production and distribution.

[0236] To facilitate the removable connection between the metering mechanism and the container (320), the metering mechanism is provided with a fastening arrangement configured to engage with a complementary fastening structure on the container (320). This mechanical connection serves both to secure the metering mechanism in place and to establish a fluidic coupling between the container (320) and the metering mechanism, thereby permitting controlled dispensing of the container’s contents.

[0237] The metering mechanism is a self-contained unit, incorporating fluid metering components and necessary connection interfaces for interaction with external drive or control systems. These connections may include, but are not limited to, electrical contacts designed to interface with a corresponding connection on the associated device (10) when the cartridge assembly is installed within the dispensing head (3) or another application-specific fluid dispensing apparatus.

[0238] FIG. 22 illustrates a high-level schematic representation of a cartridge system incorporating a detachable metering mechanism. The cartridge comprises a container (320) that includes a projection (504) extending from its lower region. The projection (504) definesa fluid port enabling access to the interior volume of the container (320). While the upper portion of the container (320) is depicted as sealed, it is contemplated that the container (320) may be configured with an accessible opening or cover to facilitate replenishment or modification of its contents as needed.

[0239] The fluid port, as defined by the projection (504), is initially sealed with an elastomeric stopper (508), which serves to prevent leakage of the contained material prior to the attachment of the metering mechanism. The metering mechanism, designated generally as (500), comprises a substantially cylindrical housing defining an internal cavity. The metering mechanism (500) is configured to be affixed to the container (320) via a threaded engagement, wherein complementary threading is provided on the external surface of the projection (504) and the internal surface of the cylindrical housing of the metering mechanism (500).

[0240] A hollow needle (506) extends from a lower interior surface of the cylindrical cavity within the metering mechanism (500). Upon threaded engagement of the metering mechanism (500) onto the projection (504), the tip of the hollow needle (506) penetrates the elastomeric stopper (508), thereby establishing a fluid conduit between the internal chamber of the container (320) and the metering mechanism (500). Once the fluid path is established, the contents of the container (320) may be metered via the integrated fluid metering components, generally indicated at (510), and subsequently discharged through an outlet nozzle (512).

[0241] Following depletion of the contents within the container (320), the metering mechanism (500) may be disengaged from the projection (504) by unthreading the connection. The metering mechanism (500) remains intact and operable for subsequent use with a replacement container (320), ensuring reusability and prolonged operational life of the metering system.

[0242] In yet another alternative embodiment, the cartridge (600) may be configured based on the principle of a syringe, wherein the plunger of the syringe serves as the metering mechanism. The dispensing head (3) is equipped with an actuator that drives the plunger in a controlled manner to precisely meter the contents of the syringe-based cartridge. The structural configuration of the cartridge may be derived from commercially available syringes, which are cost-effective, widely used in the healthcare industry, available in various sizes, and disposable after a single use.

[0243] FIG. 23 illustrates multiple syringes of varying volumes that may function as disposable cartridges within the dispensing head (3).

[0244] FIG. 24 provides a more detailed depiction of the syringe-based cartridge and its interaction with the dispensing head (3), particularly the drive mechanism for the plunger. Specifically, the cartridge (600) comprises a cylindrical barrel (602) within which a metering mechanism (604) is slidingly mounted, functioning as a plunger. The metering mechanism includes a piston (606) affixed to one end of a drive rod (608). The opposite end of the drive rod (608) features a flange (610) designed to engage with a drive mechanism, described in further detail below.

[0245] The lower end of the barrel (602) is equipped with a nozzle (612), preferably incorporating a connection mechanism for the attachment of accessories. An example of such a connection mechanism is a luer lock.

[0246] In operation, the cartridge (600) is installed in the dispensing head (3), which, for clarity, is not shown. The dispensing head (3) is designed with a fixture to securely retain the cartridge, which may take the form of a cylindrical recess tailored to receive the barrel (602). Above the fixture, a drive mechanism is provided to actuate the plunger (604). In one embodiment, the drive mechanism employs a linear actuator with precisely controlled displacement. The actuator comprises a flange (616) that interfaces with the flange (610) in a face-to-face manner. A drive rod (618) applies a downward force to the flange (616), thereby advancing the plunger in a controlled fashion to meter the cartridge’s contents, which are dispensed through the nozzle (612).

[0247] The drive rod (618) is configured for bidirectional movement, as indicated by the double-headed arrow (620). The drive rod (618) may be a threaded rod actuated by a motor, such as a stepper or servo motor, to ensure precise linear displacement.

[0248] The cartridge (600) functions similarly to previously described cartridges. In one example, the cartridge (600) is pre-filled with an active pharmaceutical ingredient (API) along with an excipient, diluent, or carrier, eliminating the need for user preparation. Optionally, prior to installation in the dispensing head (3), the contents of the cartridge (600) may be homogenized. This is achieved by placing the cartridge (600) in an appropriate adapter and subjecting the cartridge-adapter assembly to a bladeless planetary mixing cycle to homogenize the composition and remove entrapped air. Once processed, the cartridge (600) is ready for installation in the dispensing head (3).

[0249] In an alternative embodiment, the cartridge (600) may be pre-filled solely with an API at the manufacturing facility, while the end-user subsequently introduces a designated quantity of diluent, excipient, or carrier. This is facilitated as follows: at the factory, the plunger (604) isdepressed within the barrel (602) to create a predefined volume for the API. The requisite amount of API, typically in powder form, is deposited into the barrel (602) via the nozzle (612) using an appropriately sized needle. To prevent premature escape ofthe API, the nozzle (612) is sealed.

[0250] For preparation, the user removes the nozzle seal and connects an appropriate fluid line, such as a luer lock fitting, to introduce the excipient, diluent, or carrier. The addition of fluid displaces the piston (606) upwards, ensuring full mixing capacity. The cartridge (600) may then undergo homogenization in a bladeless planetary mixer, with or without an adapter.

[0251] In yet another variation, the barrel (602) may be designed as a separable structure along the plane (622), indicated by dashed lines. The two segments may be joined via a threaded connection (not shown) permitting complete opening ofthe lower barrel end for API deposition. This design eliminates the need to introduce the API through the nozzle (612). The method involves unscrewing the lower portion of the barrel (602), inverting it relative to its position in FIG. 24, and depositing the API atop the piston (606). The lower barrel portion is then reattached to the upper section. The cartridge is subsequently processed as described above, whereby the excipient, diluent, or carrier is introduced through the nozzle (612), followed by mixing in the bladeless planetary mixer with or without an adapter.

[0252] While the invention has been described with reference to certain illustrative embodiments, implementations, and examples, it will be understood by those skilled in the art that various changes, modifications, and variations may be made without departing from the scope of the invention. The described embodiments are therefore to be considered in all respects as illustrative and not restrictive. Features described in connection with one embodiment may be combined with features of other embodiments, and the invention is not limited to the specific combinations explicitly disclosed herein. The scope of the invention is defined by the appended claims, and all equivalents and modifications that fall within the scope ofthe claims are intended to be encompassed thereby.

Claims

Claims1. A method for compounding a pharmaceutical composition, the method comprising:providing a cartridge containing an active pharmaceutical ingredient and at least one excipient, diluent, or carrier;a. placing the cartridge in a bladeless planetary mixer; operating the bladeless planetary mixer to subject the cartridge to superimposed rotational and revolutionary movements, thereby dispersing the active pharmaceutical ingredient within the excipient, diluent, or carrier to form a compounded pharmaceutical composition within the cartridge;b. removing the cartridge from the bladeless planetary mixer;c. placing the cartridge in a computer-controlled dispensing device comprising a dispensing head configured to receive the cartridge; andd. operating the computer-controlled dispensing device to cause the dispensing head to dispense a metered quantity of the compounded pharmaceutical composition from the cartridge into a container.

2. The method of claim 1 , wherein placing the cartridge in the bladeless planetary mixer comprises placing the cartridge in an adapter configured to mate with the cartridge and to mechanically interface with the bladeless planetary mixer.

3. The method of claim 1, wherein operating the bladeless planetary mixer comprises operating the mixer according to a predefined mixing cycle selected based on a type of pharmaceutical composition being compounded.

4. The method of claim 1, wherein operating the bladeless planetary mixer further comprises controlling at least one of mixing speed, mixing duration, or mixing temperature.

5. The method of claim 1 , wherein the active pharmaceutical ingredient is initially present in the cartridge in a concentrated form and is dispersed into the excipient, diluent, or carrier during operation of the bladeless planetary mixer.

6. The method of claim 1, wherein operating the computer-controlled dispensing device comprises dispensing the compounded pharmaceutical composition in response to user input received via a graphical user interface.

7. The method of claim 1, wherein operating the computer-controlled dispensing device comprises dispensing the compounded pharmaceutical composition according to a dosage parameter selected from a Graphical User Interface (GUI).

8. The method of claim 1 , wherein dispensing the metered quantity comprises dispensing a plurality of discrete doses from the cartridge into one or more containers.

9. The method of claim 1 , wherein dispensing the metered quantity comprises dispensing the compounded pharmaceutical composition into a container intended for direct administration to a patient.

10. The method of claim 1, wherein the dispensing head dispenses the compounded pharmaceutical composition using at least one of pressure-driven dispensing, displacement-driven dispensing, or mechanically actuated dispensing.

11. The method of claim 1 , further comprising identifying the cartridge prior to dispensing using a cartridge identifier and adjusting dispensing parameters based on the identification.

12. The method of claim 1, further comprising storing compounding parameters associated with the cartridge in a non-transitory machine-readable storage medium.

13. The method of claim 1, wherein the method is performed in a pharmacy or compounding facility to prepare a patient-specific pharmaceutical composition.

14. The method of claim 2, wherein the adapter is configured to support cartridges of different sizes or volumes while maintaining compatibility with the bladeless planetary mixer.

15. A system for compounding a pharmaceutical composition, comprising:a. a cartridge containing an active pharmaceutical ingredient and at least one excipient, diluent, or carrier;b. a bladeless planetary mixer configured to receive the cartridge and to subject the cartridge to superimposed rotational and revolutionary movements to disperse the active pharmaceutical ingredient within the excipient, diluent, or carrier; andc. a computer-controlled dispensing device comprising a dispensing head configured to receive the cartridge after removal from the bladeless planetarymixer and to dispense a metered quantity of the compounded pharmaceutical composition from the cartridge into a container.

16. The system of claim 15, further comprising an adapter configured to mate with the cartridge and to mechanically interface with the bladeless planetary mixer to retain the cartridge during mixing.

17. The system of claim 15, wherein the bladeless planetary mixer is configured to operate according to a predefined mixing cycle selected based on a type of pharmaceutical composition being compounded.

18. The system of claim 15, wherein the bladeless planetary mixer is configured to control at least one of mixing speed, mixing duration, or mixing temperature.

19. The system of claim 15, wherein the cartridge contains the active pharmaceutical ingredient in a concentrated form prior to mixing.

20. The system of claim 15, wherein the computer-controlled dispensing device further comprises a graphical user interface configured to receive user input controlling dispensing of the compounded pharmaceutical composition.

21. The system of claim 15, wherein the computer-controlled dispensing device is configured to dispense the compounded pharmaceutical composition according to a dosage parameter selected via a graphical user interface.

22. The system of claim 15, wherein the computer-controlled dispensing device is configured to dispense a plurality of discrete doses from the cartridge into one or more containers.

23. The system of claim 15, wherein the computer-controlled dispensing device is configured to dispense the compounded pharmaceutical composition into a container intended for direct administration to a patient.

24. The system of claim 15, wherein the dispensing head is configured to dispense the compounded pharmaceutical composition using at least one of pressure-driven dispensing, displacement-driven dispensing, or mechanically actuated dispensing.

25. The system of claim 15, further comprising a cartridge identification module configured to identify the cartridge and to adjust dispensing parameters based on the identification.

26. The system of claim 15, further comprising a non-transitory machine-readable storage medium storing compounding parameters associated with the cartridge.

27. The system of claim 15, wherein the system is deployed in a pharmacy or compounding facility to prepare a patient-specific pharmaceutical composition.

28. The system of claim 16, wherein the adapter is configured to support cartridges of different sizes or volumes while maintaining compatibility with the bladeless planetary mixer.

29. An adapter for use with a bladeless planetary mixer, the adapter comprising: a body configured to be received by the bladeless planetary mixer; and a cartridge interface portion configured to mate with a cartridge containing an active pharmaceutical ingredient and at least one excipient, diluent, or carrier, wherein the adapter is configured to retain the cartridge during operation of the bladeless planetary mixer such that rotational and revolutionary motion imparted by the bladeless planetary mixer is transmitted to the cartridge to facilitate mixing of the active pharmaceutical ingredient with the excipient, diluent, or carrier within the cartridge.

30. The adapter of claim 29, wherein the cartridge interface portion is configured to receive the cartridge in a sealed or closed condition.

31. The adapter of claim 29, wherein the cartridge interface portion comprises a mechanical retention feature.

32. The adapter of claim 29, wherein the adapter is configured to accommodate cartridges of different sizes or volumes.

33. The adapter of claim 29, wherein the cartridge is a single-dose cartridge configured to dispense a single patient-specific dose of a compounded pharmaceutical composition.

34. The adapter of claim 29, wherein the cartridge is a multi-dose cartridge configured to dispense a plurality of doses of a compounded pharmaceutical composition.

35. The adapter of claim 29, wherein the cartridge contains a liquid pharmaceutical composition.

36. The adapter of claim 29, wherein the cartridge is configured for use in compounding a dosage form selected from a topical preparation, an oral preparation, a suppository, or a mucoadhesive film.

37. The adapter of claim 29, wherein the cartridge is configured to be transferred from the bladeless planetary mixer to a computer-controlled dispensing device without opening the cartridge.

38. The adapter of claim 29, wherein the cartridge comprises an outlet configured to interface with a dispensing head after removal of the cartridge from the adapter.

39. A system for mixing a pharmaceutical composition, comprising:a. a bladeless planetary mixer configured to generate superimposed rotational and revolutionary motion; andb. an adapter configured to be received by the bladeless planetary mixer and to mate with a cartridge containing an active pharmaceutical ingredient and at least one excipient, diluent, or carrier, wherein the adapter is configured to retain the cartridge during operation of the bladeless planetary mixer such that the rotational and revolutionary motion is transmitted to the cartridge to mix contents within the cartridge.

40. The system of claim 39, wherein the bladeless planetary mixer is configured to operate according to a predefined mixing cycle selected based on a pharmaceutical composition contained in the cartridge.

41. The system of claim 39, wherein the bladeless planetary mixer is configured to control at least one of rotational speed, revolutionary speed, mixing duration, or mixing temperature while the cartridge is retained by the adapter.

42. The system of claim 39, wherein the adapter is removable from the bladeless planetary mixer and configured to allow transfer of the cartridge to a dispensing device without opening the cartridge.

43. A method for making a topical pharmaceutical composition, the method comprising:a. providing a cartridge containing an active pharmaceutical ingredient in solution together with at least one excipient, diluent, or carrier;b. placing the cartridge in a computer-controlled dispensing device comprising a dispensing head configured to receive the cartridge;c. operating the dispensing head to meter a quantity of the active pharmaceutical ingredient solution from the cartridge into a container; andd. wherein the container comprises a metering mechanism configured to dispense the topical pharmaceutical composition from the container to a patient in controlled doses.

44. The method of claim 43, further comprising dispensing a pharmaceutically acceptable base formulation into the container.

45. The method of claim 44, wherein the pharmaceutically acceptable base formulation is dispensed into the container before dispensing the active pharmaceutical ingredient solution.

46. The method of claim 44, wherein the pharmaceutically acceptable base formulation is dispensed into the container after dispensing the active pharmaceutical ingredient solution.

47. The method of claim 44, wherein the pharmaceutically acceptable base formulation is dispensed from a second cartridge.

48. The method of claim 44, wherein the pharmaceutically acceptable base formulation comprises a cream, gel, ointment, lotion, paste, emulsion, or foam.

49. The method of claim 43, further comprising placing the container containing the dispensed active pharmaceutical ingredient solution and the base formulation in a planetary mixer.

50. The method of claim 49, further comprising operating the planetary mixer to mix the active pharmaceutical ingredient solution and the base formulation to form a homogeneous topical pharmaceutical composition.

51. The method of claim 49, wherein the planetary mixer is a bladeless planetary mixer configured to impart superimposed rotational and revolutionary motion.

52. The method of claim 49, wherein the container is placed in the planetary mixer in a sealed condition.

53. The method of claim 50, wherein the topical pharmaceutical composition is a patientspecific preparation.

54. The method of claim 43, wherein operating the dispensing head is controlled by software executed by a processing unit of the computer-controlled dispensing device.

55. The method of claim 54, wherein the software is configured to receive user input via a graphical user interface to specify at least one dispensing parameter.

56. The method of claim 55, wherein the at least one dispensing parameter comprises at least one of dispensed volume, dispensed mass, dispensing rate and number of dispensed doses.

57. The method of claim 54, wherein the software is configured to control dispensing of the active pharmaceutical ingredient solution based on a selected dosage form.

58. The method of claim 54, wherein the software is configured to control dispensing of the active pharmaceutical ingredient solution based on patient-specific information.

59. The method of claim 54, wherein the software is configured to coordinate dispensing of the active pharmaceutical ingredient solution and dispensing of a base formulation.

60. The method of claim 59, wherein the software is configured to control a sequence in which the base formulation is dispensed before or after dispensing of the active pharmaceutical ingredient solution.

61. The method of claim 54, wherein the software is configured to store dispensing parameters in a non-transitory machine-readable storage medium.

62. The method of claim 54, wherein the software is configured to retrieve stored dispensing parameters and automatically control dispensing of the active pharmaceutical ingredient solution based on the retrieved parameters.

63. The method of claim 54, wherein the software is configured to generate a record of dispensing operations for compliance, traceability, or quality control purposes.

64. A method for manufacturing a film dosage form, the method comprising: providing a cartridge containing an active pharmaceutical ingredient together with at least one excipient, diluent, or carrier;a. placing the cartridge in a computer-controlled dispensing device comprising a dispensing head configured to receive the cartridge and a drying mechanism integrated with the dispensing device;b. operating the dispensing head to dispense a controlled quantity of contents of the cartridge onto a substrate; andc. operating the drying mechanism to remove solvent or moisture from the dispensed material to thereby dry the dispensed material and form a pharmaceutical film dosage form.

65. The method of claim 64, wherein the active pharmaceutical ingredient is present in the cartridge in solution or suspension form.

66. The method of claim 64, wherein the substrate comprises a removable support, mold, or carrier surface.

67. The method of claim 64, wherein operating the dispensing head comprises dispensing the contents of the cartridge according to a predefined dispensing pattern selected via a graphical user interface.

68. The method of claim 64, wherein operating the drying mechanism comprises at least one of applying heated air, infrared radiation, resistive heating, or vacuum-assisted drying.

69. The method of claim 64, wherein operating the drying mechanism is controlled by software executed by a processing unit of the computer-controlled dispensing device.

70. The method of claim 64, wherein the dispensing pattern is controlled to define at least one of film shape, surface area, thickness, or dosage strength.

71. The method of claim 64, wherein the pharmaceutical film dosage form is a mucoadhesive film.

72. The method of claim 64, further comprising separating the pharmaceutical film dosage form into individual doses after formation.

73. The method of claim 64, wherein the pharmaceutical film dosage form is a patientspecific dosage form.

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