Medication dispensing systems, methods, and devices

Abstract

Systems, methods, and devices disclosed herein include a medication dispensing device for distributing a prescription medication to a user. The medication dispensing device includes a pharmaceutical inventory system; a packaging inventory system; and a medication packing system. The medication packing system receives one or more empty capsules from the packaging inventory system, fills the one or more empty capsules with a quantified pharmaceutical received from the pharmaceutical inventory system, resulting in one or more filled capsules, and fills an empty container received from the packaging inventory system with the filled capsules, resulting in a filled container. Moreover, a user interface is operable to receive a patient identifier (e.g., QR code) from a user, and the quantified pharmaceutical and the personalized label are based on the patient identifier received at the user interface. The medication dispensing device can combine multiple different prescriptions into a single poly-pill for the patient. Also provided are polypill formulations generated by the medication dispensing devise and methods of use thereof.

Description

Atty. Docket No. UTSD.P4571WO / 1001378524TITLE MEDICATION DISPENSING SYSTEMS, METHODS, AND DEVICES CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 751 ,695 filed on January 30, 2025, and U.S. Provisional Application No. 63 / 912,172 filed on November 5, 2025, the disclosure of both is hereby incorporated by reference in their entireties.BACKGROUND1. Field

[0002] The present disclosure relates to pharmaceutical distribution systems and multi-drug single pill formulations for heart failures.2. Discussion of Related Art

[0003] Heart failure (HF) represents a major public health challenge, affecting more than 6 million Americans with 5-year mortality rates approaching 50%. Guideline-directed medical therapy (GDMT) improves clinical outcomes among patients with HF with reduced ejection fraction (HFrEF). Contemporary GDMT involves the use of four medication classes: beta blockers, renin-angiotensin-system inhibitors (RASi), sodium-glucose co-transporter inhibitors (SGLT2i), and mineralocorticoid receptor antagonists (MRAs). The use of these medications in combination reduces all-cause mortality by approximately 50% compared with conventional two-drug therapy. Nonetheless, overall utilization of GDMT is low. Only 15% of patients hospitalized with HFrEF receive any dose of quadruple GDMT, and up-titration to optimal doses is even more rare. Recent evidence from the STRONG-HF trial underscores the clinical relevance of these implementation gaps. In that trial, achievement of optimal GDMT following HF hospitalization was associated with a 34% lower risk of all-cause death or HF readmission.

[0004] Suboptimal utilization of GDMT stems from both provider-level and patient-level barriers. Provider-level factors include therapeutic inertia and concerns about adverse effects. Patient-level barriers include polypharmacy burden, complex dosing regimens, and high medication costs. Several implementation strategies have been tested to improve use of GDMT, primarily targeting provider-level barriers through virtual consultations, clinician education, dedicated GDMT clinics, and feedback reports with continuous quality improvement. These interventions have demonstrated heterogeneous effects on GDMT uptake, with some having only a modest increase and others showing no improvement. Furthermore, data regarding the impact of such interventions on clinical outcomes are lacking. Lastly, most tested interventions do not adequately address patient-level barriers to GDMT, highlighting the need for new approaches.301612543 - 1 -Atty. Docket No. UTSD.P4571WO / 1001378524

[0005] Typically, a patient must travel to the pharmacy to fulfill their prescription and receive the prescribed medication. The pharmacy can receive the prescription details directly from the doctor or from the patient. In both cases, the patient must arrive at the pharmacy to receive the prescription in-person. Sometimes, prescriptions can take hours to fulfill and the patient must wait. Pharmacies can require multiple days to fulfill the prescription when the medication is out of stock at that particular location. As such, it can be difficult for patients with multiple, different prescriptions to get all of their prescriptions fulfilled. Additional difficulties arise from managing dosage schedules for multiple prescriptions.

[0006] It is with these observations in mind that the presently disclosed technology was conceived.SUMMARY

[0007] Systems, methods, and devices disclosed herein can address the aforementioned issues. For instance, a medication dispensing system can include a pharmaceutical inventory system; a packaging inventory system; and / or a medication packing system. The medication packing system can be operable to receive one or more empty capsules from the packaging inventory system, and / or fill the one or more empty capsules with a quantified pharmaceutical received from the pharmaceutical inventory system, resulting in one or more filled capsules. Also, the medication packing system can fill an empty container received from the packaging inventory system with the filled capsules, resulting in a filled container. Furthermore, the medication dispensing system can include a labelling system operable to provide a personalized label corresponding to the quantified pharmaceutical. The medication dispensing system can also include a user interface operable to receive a patient identifier from a user of the medication dispensing system. The quantified pharmaceutical and the personalized label can be based on this patient identifier received at the user interface.

[0008] In some examples, the pharmaceutical inventory system, the packaging inventory system, the medication packaging system, and / or the labelling system are at least partly contained within a housing of the medication dispensing system. The housing can include wheels providing mobility to the medication dispensing system. Additionally, the pharmaceutical inventory system can store a plurality of different medications, and / or the medication packing system can be operable to fill an empty capsule with the plurality of different medications, based on a plurality of prescriptions associated with the patient identifier, such that the one or more filled capsules includes a poly-medication pill corresponding to the plurality of prescriptions.

[0009] In some instances, the user interface can be operable to receive a plurality of different patient identifiers from a plurality of patients, and / or the medication packing system can be301612543 - 2 -Atty. Docket No. UTSD.P4571WO / 1001378524operable to fulfill a plurality of different prescriptions, using different quantified pharmaceuticals from the pharmaceutical inventory system, based on the plurality of different patient identifiers. The medication dispensing system can also include a plurality of cassettes of the pharmaceutical inventory system. A first individual cassette of the plurality of cassettes can store a first drug in bulk form, and a second individual cassette of the plurality of cassettes can store a second drug in bulk from, with the second drug being a different drug than the first drug. Also, the pharmaceutical inventory system can include one or more sensors to detect a quantity of a stored drug in an individual cassette of the plurality of cassettes. Additionally, the medication dispensing system can include an access door to the plurality of cassettes, operable responsive to a determination that the quantity of the stored drug in the individual cassette is below a predetermined threshold value. Moreover, the labelling system can apply the personalized label to the filled container or the empty container. The labelling system can print the personalized label and can distribute, to the user, the personalized label separate from the filled container. Furthermore, the packaging inventory system can include a first color-coded capsule corresponding to a first dosage time period and a second color-coded capsule corresponding to a second dosage time period.

[0010] In some scenarios, a medication dispensing device can include a pharmaceutical inventory system; a packaging inventory system; and / or a medication packing system. The medication packing system can be operable to receive one or more empty capsules from the packaging inventory system, fill the one or more empty capsules with a quantified pharmaceutical received from the pharmaceutical inventory system, resulting in one or more filled capsules, and / or fill an empty container received from the packaging inventory system with the filled capsules, resulting in a filled container. The medication dispensing device can also include a labelling system operable to provide a personalized label corresponding to the quantified pharmaceutical. Furthermore, the medication dispensing device can include a housing at least partly enclosing the pharmaceutical inventory system, the packaging inventory system, the medication packing system, and / or the labelling system. The medication dispensing device can also include a user interface, coupled to the housing, operable to receive a patient identifier from a user of the medication dispensing system. Moreover, the quantified pharmaceutical and the personalized label can be based on the patient identifier received at the user interface.

[0011] In some examples, the medication dispensing device can include a code scanner operable to detect the patient identifier. Additionally, the medication dispensing device can include a refrigeration system operable to maintain a predefined temperature at the pharmaceutical inventory system. The medication dispensing device can further include a battery power system operable to provide power to the refrigeration system, and / or one or301612543 - 3 -Atty. Docket No. UTSD.P4571WO / 1001378524more cameras coupled to the housing and operable to generate video data of an exterior area proximate to the medication dispensing device. Furthermore, the patient identifier can be included in at least one of a bar code, a QR code, a written or printed prescription on paper, and / or a prescription data transmission received at a communication system of the medication dispensing device. The patient identifier can be provided to the medication dispensing device via at least two independent channels as part of a verification procedure.

[0012] In some instances, a method of dispensing medication to a patient can include storing medication at a pharmaceutical inventory system of a medication dispensing device; storing a plurality of empty capsules and a plurality of empty containers at a packaging inventory system of the medication dispensing device; receiving, at a user interface of the medication dispensing device, a patient identifier from a user of the medication dispensing system; filling, using a medication packing system of the medication dispensing device, one or more capsules of the plurality of empty capsules with a quantified pharmaceutical received from the pharmaceutical inventory system, resulting in one or more filled capsules, the quantified pharmaceutical being based on the patient identifier; filling, using the medication packing system, an empty container received from the packaging inventory system with the filled capsules, resulting in a filled container; and / or providing, using a labelling system of the medication dispensing device, a personalized label corresponding to the quantified pharmaceutical.

[0013] In some examples, the method can further include dispensing the filled container to the user via a dispensing outlet formed into a housing of the medication dispensing device. Moreover, the method can include detecting, using one or more sensors, that an amount of a particular pharmaceutical stored at the pharmaceutical inventory system is below a predetermined threshold value, and / or generating a notification indicating that the amount of the particular pharmaceutical is below the predetermined threshold value.

[0014] Also provided are polypill formulations formed by any medication dispensing system disclosed herein. In various aspects, the polypill formulation may comprise a beta blocker, a renin-angiotensin-system (RAS) inhibitor, a sodium-glucose co-transporter 2 inhibitor (SGLT2i) and / or a mineralocorticoid receptor antagonist (MRA). In various aspects, the beta blocker comprises metoprolol, optionally metoprolol succinate; the SGLT2i comprises empagliflozin; the MRA comprises spironolactone; or any combination thereof. In still further aspects, the polypill formulation may comprise (a) 10 mg of empagliflozin, (b) 12.5 mg of spironolactone, and (c) 25 mg, 50 mg, 100 mg, or 150 mg of metoprolol succinate.

[0015] Also provided are polypill formulations comprising (a) a first pill comprising a beta blocker, (b) a second pill comprising a sodium-glucose co-transporter 2 inhibitor (SGLT2i), and (c) a third pill comprising a mineralocorticoid receptor antagonist (MRA), and (d) a gel301612543 - 4 -Atty. Docket No. UTSD.P4571WO / 1001378524capsule, wherein the gel capsule of (d) encapsulates the first, second, and third pills of (a), (b), and (c). In various aspects, the polypill formulation may comprise (a) 25 mg, 50 mg, 100 mg, or 150 mg of metoprolol succinate, (b) 10 mg of empagliflozin, and / or (c) 12.5 mg of spironolactone.

[0016] Also provided are methods of treating a disease or condition in a subject, the method comprising administering a polypill formulation disclosed herein to the subject. In various aspects, the disease or condition comprises heart failure, optionally wherein the disease or condition comprises heart failure with reduced ejection fraction (HFrEF).BRIEF DESCRIPTION OF THE FIGURES

[0017] FIG. 1 illustrates an example system including a medication dispensing device which generates and dispenses one or more medications.

[0018] FIG. 2 illustrates an example system including a medication dispensing device with a pharmaceutical inventory system, a packaging inventory system, and / or a medication packing system.

[0019] FIG. 3 illustrates an example system including a medication dispensing device with a labelling system and a dispensing system.

[0020] FIG. 4 illustrates an example system including a plurality of medication dispensing devices in a wireless network architecture.

[0021] FIG. 5 depicts an example method of dispensing a medication using a medication dispensing device which can be performed by any of the system(s) disclosed herein.

[0022] FIG. 6 depicts a consolidated standards of reporting trials (CONSORT) diagram of the disclosure.

[0023] FIGS. 7A-7C depict clinical outcomes, health status, and hierarchical composite endpoint in patients treated with polypill versus enhanced usual care. FIG. 7A shows a representation of the cumulative number of composite clinical HF events or death over followup. The solid line marked “E” represents the enhanced usual care group, and the solid line marked “P” represents the polypill group, with dashed lines indicating 95% confidence intervals. FIG. 7B shows a representation of the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) trajectories over 6 months by treatment group. The solid line marked “E” represents the enhanced usual care group, and the solid line marked “P” represents the polypill group, with dashed lines indicating 95% confidence intervals. FIG. 7C shows the win ratio for the composite hierarchical end point, overall and the percent of ins, losses, and ties by each component of the composite.301612543 - 5 -Atty. Docket No. UTSD.P4571WO / 1001378524

[0024] FIGS. 8A-8C depict GDMT utilization in the polypill and enhanced usual care arms over the study period. FIG. 8A shows a representation of the utilization of quadruple GDMT, defined as prescription of all four medication classes: beta-blocker, mineralocorticoid receptor antagonist, renin-angiotensin-aldosterone system inhibitor, and SGLT2 inhibitor. FIG. 8B shows a representation of the utilization of optimal GDMT, defined as prescription at >50% of TDD of beta-blocker, >50% of TDD ARB / ACEi or any dose ARNi, any dose MRA, and any dose of SGLT2L FIG. 8C shows a representation of the modified Heart Failure Collaboratory score, which ranges from 0-100, with higher scores indicating better medication optimization across the four GDMT components.

[0025] FIG. 9 depicts LVEF at 6 months across pre-specified subgroups. Values are adjusted least square means (95% Cl) and between group differences (95% Cl) at 6 months. All models adjusted fortreatmentxtime, age, sex, race, ethnicity, NYHA class, HF etiology, HF chronicity, eGFR, baseline NT-proBNP, and baseline LVEF. A random intercept for participant ID was included to account for within-subject correlation. P-interaction represents a three-way interaction between treatment arm, time, and the subgroup variable. Analysis includes 184 participants with baseline LVEF <55% and both baseline and 6-month MRI measurements. Abbreviations: Cl, confidence interval; eGFR, estimated glomerular filtration rate; HF, heart failure; LVEF, left ventricular ejection fraction; MRI, magnetic resonance imaging; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association.

[0026] FIGS. 10A-10D depicts utilization of individual GDMT classes (Beta Blocker (FIG.10A), MRA (FIG. 10B), SGT2i (FIG. 10C) and RASi (FIG. 10D)) over the study period across treatment groups. For each study period, Polypill group is represented by the left bar and enhanced usual care group is represented by the right bar.DESCRIPTION

[0027] It will be appreciated that numerous specific details are set forth in order to provide a thorough understanding of the examples described herein. However, it will be understood by those of ordinary skill in the art that the examples described herein can be practiced without these specific details. In other instances, methods, procedures and components have not been described in detail so as not to obscure the related relevant feature being described. Also, the description is not to be considered as limiting the scope of the examples described herein. The drawings are not necessarily to scale and the proportions of certain parts may be exaggerated to better illustrate details and features of the present disclosure.II. Medication Dispensing Systems

[0028] The systems, methods, and devices disclosed herein include an example system for dispensing an individualized medication to fulfill a patient’s prescription by using a medication301612543 - 6 -Atty. Docket No. UTSD.P4571WO / 1001378524dispensing device. The medication dispensing device can include mechanical features forming various sub-assemblies for measuring and encapsulating loose drug powder into capsules, and compiling and packaging those capsules into a prescription pill bottle. For instance, multiple components of the medication dispensing deice can operate together to receive prescription data from the patient, fill empty capsules responsive to the prescription data, fill an empty container with the filled capsules, and distributing the filled container to the patient. Furthermore, the medication dispensing device can combine multiple different prescriptions into a single poly-pill for the patient, thus simplifying their dosage schedule. Providing medications as one capsule (e.g., rather than three or four or more pills) can improve compliance, reduce the number of pills a patient is responsible for, and still provide the necessary medications at the appropriate dosage.

[0029] The medication dispensing device may include mechanical features to facilitate automated, direct filling of capsules with a programmed amount of drug material (e.g., present in raw, powder form). Additionally, the medication dispensing device can have a smaller form factor than industrial pill filling machines, such that the medication dispensing device is small enough to fit into a van / truck for moving. The smaller form factor can also make the medication dispensing device user friendly. The medication dispensing device can be deployed in community rec centers, churches, or housing authority apartments, spaces where medications are typically not available to at-risk populations. The medication dispensing device may also be placed in a pharmacy to reduce workforce burden. The medication dispensing device may be smaller than industrial pill filling machines, providing less pills in total, but bringing those pills to more people, directly, and in a customized formulation particularized to the requesting patient. This can reduce barriers between the patient and the pharmacy by reducing transit time, and can make prescriptions available outside typical store open hours. The flexibility of using manually entered prescription input can provide patients with several ways to access their prescription and can create easy access to medications while not relying on protected medical information beyond name and DOB for identity verification (e.g., or no more information than is typically provided to a pharmacist).

[0030] Additional advantages of the systems, methods, and devices discussed herein will become apparent from the detailed description below.

[0031] FIG. 1 illustrates an example system 100 including a medication dispensing device 102 which dispenses an individualized medication for fulfilling a patient’s prescription. The medication dispensing device 102 can include a pharmaceutical inventory system 104 for storing and managing a plurality of different medications (e.g., in bulk form). The medication dispensing device 102 can also include a packaging inventory system 106 which stores and manages non-medication supplies used for fulfilling the prescription, such as empty capsules301612543 - 7 -Atty. Docket No. UTSD.P4571WO / 1001378524and empty containers (e.g., bottles). Additionally, the medication dispensing device 102 can include a medication packing system 108 which performs steps to fill the empty capsules with the loose-form medication from the pharmaceutical inventory system 104, resulting in filled capsules. The medication packing system 108 can also fill the empty containers with the filled capsules, further resulting in filled containers. Moreover, the medication dispensing device 102 can include a labelling system 110 which generates and distributes a personalized label corresponding to the prescription and patient. Any or all of these components can be fully or at least partially contained within a housing 112 of the medication dispensing device 102

[0032] Furthermore, in some examples, the operations of the medication dispensing device 102 can be initiated by a user providing a patient identifier 114 to the medication dispensing device 102. For instance, the medication dispensing device 102 can include a user interface 116 (e.g., a graphical user interface (GUI), a touchscreen, a scanner, a keyboard, buttons, etc.) which the user can interact with to provide the patient identifier 114 to the medication dispensing device 102. The user interface 116 can include a scanner and the patient identifier 114 can include a bar code, a QR code 118, and / or a written or printed document, which can be read by the scanner. Additionally or alternatively, the patient identifier 114 can be provided to the medication dispensing device 102 via a communication system 120 of the medication dispensing device 102. For example, the patient identifier 114 can be received using a wireless network interface of the medication dispensing device 102 which receives a wireless data transmission over a network 122, for instance, from a pharmacy device, a hospital device, a clinic device, or so forth. In some examples, the patient identifier 114 can be received from one or more prescription database(s) 124 which store a plurality of different prescriptions for different patients on secure servers. In some scenarios, the patient identifier 114 may provide access to a plurality of different prescriptions stored at different locations, and / or received from different sources, such that the plurality of prescriptions can be aggregated together by the medication dispensing device 102.

[0033] In some instances, the patient identifier 114 can include data corresponding to the patient and / or the prescription associated with the patient. For instance, the bar code and / or QR code 118 can contain information (e.g., and / or a link to stored data) related to the patient such as a patient name, a patient birthday, a patient address, a patient social security number, a patient private ID number, a patient pin, a patient password, and so forth. The patient identifier 114 can also include information related to one or more prescription(s) associated with the patient, such as one or more medication names, one or more medication dosage instructions, one or more medication warnings, one or more medication prescription quantities, and / or other physician notes or instructions related to the patient’s prescription(s).301612543 - 8 -Atty. Docket No. UTSD.P4571WO / 1001378524

[0034] Furthermore, the patient identifier 114 can be associated with data for a plurality of prescriptions for different medications associated with the patient (e.g., which can be written by one doctor or a plurality of different doctors). Responsive to receiving the patient identifier 114, the medication dispensing device 102 can initiate the steps discussed herein to fulfill the prescription(s) associated with the patient identifier 114. This can include creating and packaging poly-pills which include a plurality of medications aggregate together in a customized formula for that particular patient. Furthermore, upon generating the filled container of the one or more prescriptions, the medication dispensing device 102 can use a dispensing system 126 to expel the filled container from the medication dispensing device 102 and / or provide the filled container to the user, thus resulting in one or more fulfilled prescription(s) 128. Additionally, the medication dispensing device 102 can include one or more wheels 130, such as four lockable wheels, which provide a mobility capability for the medication dispensing device 102. As such, the medication dispensing device 102 can be move from one distribution location to another easily, for instance, on a weekly, monthly, or yearly basis. Each of these components is discussed in greater detail below.

[0035] FIG. 2 depicts an example system 100 with a medication dispensing device 102 including the pharmaceutical inventory system 104, the packaging inventory system 106, and / or the medication packing system 108. The system 100 depicted in FIG. 2 can be similar to, identical to, and / or can form at least a portion of the system 100 of FIG. 1.

[0036] In some examples, the pharmaceutical inventory system 104 can include a plurality of medication cassettes 202. The plurality of medication cassettes 202 can store the predistributed medications in a bulk form (e.g., as powders, liquids, granules, inhalants, etc.) . Individual cassettes of the plurality of medication cassettes 202 can each correspond to a particular medication. Moreover, a cassette can store a particular combination of a plurality of medications (e.g., which are commonly taken together) in a predefined medication ratio. Additionally or alternatively, the plurality of medication cassettes 202 can store premeasured dosages of the medications (e.g., in 1 mg doses, 2 mg doses, 3 mg doses, 4 mg doses, 5 mg doses, 10 mg doses, 20 mg doses, 50 mg doses, and so forth). The premeasured dosages can be stored as compacted powders, cups of liquid, packs of liquid, in arrays of square or circular receptacles, in small vials, capsules, or so forth. Additionally, the pharmaceutical inventory system 104 can include one or more scales and / or sensors 204 for determining an amount of medication stored in the plurality of medication cassettes 202. These scales and / or sensors 204 can include a weight scale, an imaging device or light sensor, a camera, a switch triggered when a volume level falls below a predetermined height, various combinations thereof, and so forth. In some scenarios, individual cassettes of the plurality of medication cassettes 202 can have corresponding individual sensors to generate quantity data for the301612543 - 9 -Atty. Docket No. UTSD.P4571WO / 1001378524individual cassettes. Furthermore, the pharmaceutical inventory system 104 can include a refrigeration system 206 (e.g., heat exchangers, compressors, evaporative coolers, HVAC systems, thermocouples, and so forth) to control the temperature for raw drug material, for instance, to maintain the plurality of medications cassettes 202 and the medications therein at a predetermined threshold temperature value.

[0037] Furthermore, in some scenarios, the packaging inventory system 106 of the medication dispensing device 102 can include the various supplies used by the medication packing system 108 to quantize the medication and / or generate the filled capsule(s) and filled bottle(s). These supplies can include one or more capsule(s) 208 (e.g., empty capsules, partially empty capsules, and / or partially or fully pre-filled capsules). The capsule(s) 208 can be stored in a capsule cassette of the packaging inventory system 106 and / or can be aligned as a plurality of half-capsules having their opening side facing upward and / or in a same direction. The packaging inventory system 106 can also include one or more bottles 210 (e.g., empty bottles and / or bottles at least partially filled, for instance, with a moisture absorber) and / or labels 212 (e.g., blank labels).

[0038] In some instances, the medication packing system 108 can include an input port 214 for receiving data, such as the data of the prescription details represented by the patient identifier 114. The medication packing system 108 can convert the data into machine-readable instructions for performing the capsule filling procedure, the bottle filling procedure, and / or the bottle dispensing procedure (e.g., using one or more memory storage devices and / or processors, as discussed in greater detail below regarding FIG. 4). The instructions can be sent as a control signal to a pill filler 216 including a drug quantification system 218 and / or a medication compressor 220. For instance, the drug quantification system 218 can receive and / or extract a particular, measured quantity of medication 222 from the plurality of cassettes 202, and can distribute the measured quantity of the medication 222 into one or more empty capsules 224. The measured quantity of the medication 222 can be at least partly based on the data received from the patient identifier 114. Then, the medication compressor 220 can apply pressure (e.g., using a press arm) to the loose drug inside the capsule to cause the medication to compress inside the capsule 208. Also, in scenarios where the medication packing system 108 creates tablets rather than or in addition to capsules, the compressor 220 can compress the quantity of medication 222 into a pressed tablet.

[0039] Once the empty capsule(s) 224 have been filled with the quantified medication 222 (e.g., and / or a plurality of different quantified medications 222), the filled capsules 226 can be provided to a bottle filler 228. The bottle filler 228 can include the components for receiving an empty bottle 230 from the packaging inventory system 106, and filling the empty bottle 228 with the filled capsules 224. For example, the bottle filler 228 can include a pill quantification301612543 - 10 -Atty. Docket No. UTSD.P4571WO / 1001378524system 232 which uses one or more ramps, chutes, and / or sensors to quantify an amount of filled capsules 224 (e.g., based on data from the patient identifier 114), and provide the predetermined amount of filled capsules 224 into the empty bottle 230, resulting in a filled bottle 234. Furthermore, the bottle filler 228 can include a sealing system 236 which can provide an adhesive-based seal over the top opening of the filled bottle 234, and / or can provide a lid 238 to close the filled bottle 234. The bottle filler 234 can include various sensors (e.g., weight sensors and / or cameras) to ensure a proper amount of filled capsules 224, according to the prescription data, are provided into the empty bottle 230.

[0040] In some examples, the pharmaceutical inventory system 104 can monitor inventory by sensing the weight of the loose powder (e.g., drug material). Upon sensing a predefined weight difference (e.g., a set amount), the medication dispensing device can generate and send a notification to a central management system device indicating the need for a refill. The system 100 can also include one or more presets of how many pills the medication dispensing device 102 is expected to create, and estimates of how much powder is expected be used to create those pills. Once the machine detects that an estimate has been reached, an alert can be sent to the central management system device (e.g., the central data management device 408 in FIG. 4) to request a restock of that particular medication. Furthermore, the medication dispensing device 102 can include back door by which a re-supplier can refill loose powder receptacles during restocking. The refills can be done manually and in bulk. For example, an employee or pharmacist can be provided with a cassette, bottle, or pouch of raw drug material and can be dispatched to load the loose powder into the medication dispensing device 102 (e.g., by replacing one of the plurality of medication cassettes 202 and / or by pouring the loose powder into the corresponding emptied cassette).

[0041] In this way, the system 102 can use a centralized data system for inventory management of a plurality of medication dispensing devices 102 in operation, for instance, at a plurality of different locations around the country and the world. The system 100 can use the centralized data management system (e.g., or a plurality of compartmentalized / regionalized management systems) to alert support teams to any technical issues, inventory needs, and / or other issues which may arise with the medication dispensing devices 102. Individual medication dispensing devices 102 can each have an internal system to monitor for technical issues and restock needs, and this information can be shared with the centralized data management system, which can be accessible by the vendor. The centralized data management system is discussed in greater detail below regarding FIG.4.

[0042] In some examples, the medication dispensing device 102 can include various hardware components for constructing the pharmaceutical inventory system 104, the301612543 - 11 -Atty. Docket No. UTSD.P4571WO / 1001378524packaging inventory system 106, the medication packing system 108, the labelling system 110, and / or the dispensing system 126. For example, the pharmaceutical inventory system 104, the packaging inventory system 106, the medication packing system 108, the labelling system 110, and / or the dispensing system 126 can include one or more capsule magazines, horizontal or vertical sorting fingers, sorting blocks, tamper pins, dosing disks, upper or lower segments, alignment pins, mounting panels, central turn tables, control boxes, power boxes, interior mounting walls, conveyor belts, gear shafts, gripping arms, chutes (e.g., capsule alignment chutes), sensor mounts, and the like. These components can be formed of machined, molded, and / or extruded metal or plastic, and can be assembled together into the sub-assemblies disclose herein, which can be contained in the housing 112 and / or can be in communication with the computing device 404 discussed herein.

[0043] In some cases, it is to be understood that the disclosed sub-assemblies (e.g., the pharmaceutical inventory system 104, the packaging inventory system 106, the medication packing system 108, the labelling system 110, and / or the dispensing system 126) can comprise separate modules and / or combinations of modules. Moreover, any of the components of the pharmaceutical inventory system 104, the packaging inventory system 106, the medication packing system 108, the labelling system 110, or the dispensing system 126 can be combined with any other components of the pharmaceutical inventory system 104, the packaging inventory system 106, the medication packing system 108, the labelling system 110, and / or the dispensing system 126, such that these sub-assemblies can be at least partially integrated together into various combinations of the different sub-assemblies disclosed herein.

[0044] In some examples, the medication dispensing device 102 can use these components to create one or more polypills corresponding to the prescription. The polypill can include two or more medications combined together, such as medications for treating comorbidities including diabetes, hypertension, and / or cardiovascular disease. Another example can include medication combinations for providing cancer combination therapy, or those drugs included on the WHO essential drug list (e.g., primary care), tuberculosis medications, and / or HIV medications.

[0045] In some scenarios, the medication dispensing device 102 can use capsules 208 that are differentiated by color to indicate a particular time of day for taking. For instance, night time medication can fill a darker colored capsule (e.g., dark blue) and day time and / or morning medication can fill a lighter colored capsule (e.g., white). Additionally or alternatively, instructions can be printed directly onto the capsules, such as the words “morning,” “day, “night,” a particular dosage time (e.g., “9:00 am”), multiple dosage times, a day indicator (e.g.,301612543 - 12 -Atty. Docket No. UTSD.P4571WO / 1001378524“Saturday,” “even days,”) multiple different day indicators for different capsules, and / or combinations thereof.

[0046] FIG. 3 depicts an example system 100 with the medication dispensing device 102 including the labelling system 110 and / or the dispensing system 126. The system 100 depicted in FIG. 3 can be similar to, identical to, and / or can form at least a portion of the system 100 of FIG. 1.

[0047] In some examples, the labelling system 110 can aggregate label data 302 from the patient identifier onto a blank label 212 using a printer 304, resulting in a printed label 306. For instance, the label data 302 can include a one or more drug name(s) 308, a patient name 310, dosage instructions 312, a provider name 314, an indication of the color-coded capsule meanings, and / or any other doctor notes or warnings associated with the medications. By way of example, the label data 302 can include a printed image of hand written notes or printed notes generated by a doctor or pharmacist, which are scanned by the medication dispensing device 102 (e.g., captured by a camera of the associated with the user interface 116.) Moreover, the label data 302 can include instructions provided to the patient which highlight any identifiers printed onto the filled capsules 226. The printed label 306 can be attached directly onto the filled bottle 234 (e.g., using an adhesive) after filling, or the empty bottle 230 prior to filling, resulting in a labelled bottle 316. Additionally or alternatively, the printed label 306 can be distributed to the user separately from the filled bottle 234, such that the user can self-administer the printed label 306 onto the filled bottle 234.

[0048] Furthermore, the filled bottle 234 and / or the labelled bottle 316 can be provided to a dispensing system 126 used to distribute the filled bottle 234 and / or the labelled bottle 316 to a user. The dispensing system 126 can include one or more outlet opening(s) 318 for distributing the filled bottle 234 and / or the labelled bottle 316, which can include a holding space and / or an access window for the dispensed bottle. Additionally, in some instance, the dispensing system 126 can include another outlet opening 318 and / or another holding area for dispensing the printed label 306. Moreover, the dispensing system 126 can include one or more distribution sensor(s) 320 to assist in providing the filled bottle 234 and / or the labelled bottle 316 to the user. The distribution sensor(s) 320 can include a security camera or proximity camera, a motion sensor, an eye scanner, a fingerprint scanner, other identity verification sensors, a weight sensor (e.g., for confirming a presence of the filled bottle 234 and / or the labelled bottle 316 in a holding area), and / or combination thereof. The dispensing system 126 can also generate and / or present one or more user interface indicators 322 to alert the user that the filled bottle 234 and / or the labelled bottle 316 is ready to be taken from the medication dispensing device 102. The user interface indicators 322 can include one or301612543 - 13 -Atty. Docket No. UTSD.P4571WO / 1001378524more of a text or icon presented on the user interface 116 (e.g., a touch screen or other GUI), an LED indicator, an audio alert via an external speaker, or combinations thereof.

[0049] In some examples, the sub-assemblies of the medication dispensing device 102 (e.g., the medication packing system 108, the labelling system 110, the dispensing system 126, the pharmaceutical inventory system 104, the packaging system 106) and / or the components therein can be provided a voltage (e.g., a DC voltage) by a power supply 324. The power supply 324 can include a battery cell, a lithium-ion battery, a rechargeable battery, a solar panel, and / or a power cable (e.g., such as an AC power cable and / or a DC converter). Furthermore, the power supply 324 can include a back-up power supply, activated when a power loss is detected (e.g., to support the dispensing system 126 and / or the refrigeration system 206), such as a power generator, a back-up lithium-ion battery a back-up solar panel, or so forth.

[0050] FIG. 4 illustrates an example system 100 including a wireless network architecture 402 for implementing the medication dispensing system(s) disclosed herein. In some instances, the wireless network architecture 402 can include a plurality of medication dispensing devices 406 distributed to a plurality of different locations and communicating with a central data management device 408. The system 100 depicted in FIG. 4 can be similar to, identical to, and / or can form at least a portion of the system 100 of FIG. 1.

[0051] Additionally, the one or more computing device(s) 404 of the wireless network architecture 402 can perform various informatics operations for dispensing the medication. The informatics operations can be used to optimize drug combinations and dispensing, for instance, by using the data of the QR codes 118 or direct prescriptions sent to the machine from a pharmacy, and / or by using provider codes or prescription codes input directly into machine. For example, in some scenarios, IT personnel can use data from the informatics operations to perform maintenance, re-filling, and / or optimization procedures. The informatics data can be used to regulate the amount of active ingredient and / or drug material in the capsules.

[0052] Furthermore, the informatics operations can provide additional avenues of prescription fulfillment. For instance, the prescription data can be provided by scanning the QR code 118, and / or can be sent via Wi-Fi, internet, or cellular data from the provider’s office, pharmacist’s computer, or patient’s phone. Informatics may inform an algorithm controlling pill production, such as polypill combination, managing drug substitutions, managing drug-to-drug interactions, and / or combinations thereof. The system 100 can collect and / or generate large data sets of this information which can be used by one or more machine-learning models to further optimize the medication dispensing operations disclosed herein. Furthermore,301612543 - 14 -Atty. Docket No. UTSD.P4571WO / 1001378524informatics operations can facilitate communications with a physician about changes to the prescription based on drug combination needs.

[0053] In some instances, a computing device 404 within the medication dispensing device 102 can store data, perform any of the data analytics operations discussed herein, and / or can send the information to the different sub-assemblies for filling and dispensing of the prescriptions to patients. For instance, a medication dispensing operation can include the patient receiving their prescription-specific QR code 118 from their physician, either in a message, email, or other communication from their doctor’s office, from the hospital upon discharge, or combinations thereof. The QR code 118 can be available through MyChart or another electronic medical record application (e.g., a physician office portal) or can be shared via text or email. The QR code 118 may also be printed and provided to the patient physically if they do not have a mobile device, along with a code of letters, numbers, and / or symbols which may be entered manually (e.g., at the user interface 116), along with patient name, DOB, and so forth.

[0054] Additionally or alternatively, example prescription fulfillment options include a written prescriptions (e.g., using handwriting recognition software) and, where allowable by local laws, patients may be able to submit their own medication lists for combination, such as over-the-counter medications. That said, prescriptions provided by a physician can include using a telephone-based system integrated with the medication dispensing device 102. The physician requesting prescription fulfillment (e.g., via the telephone-based system or other electronic transmission system) can provide a unique ID, and / or the system 100 can use voice recognition of the physician after an initial set-up procedure or a verification procedure (e.g., two-step authentication) for the physician. Also, in some circumstances, the unique code can be provided to the patient who can, in turn, enter the unique code via a manual input (e.g., at the user interface 116).

[0055] In some examples, a centralized data system can use the central data management device 408 to monitor and / or support the management of patient, inventory, and security data needed for the operations disclosed herein. Patient data can be stored at the central data management device 408, and can be available for transmission to individual machines. For instance, information used to identify and verify the patient for prescription dispensing (e.g., a name, a DOB, a code associated with prescription, or so forth) can be un-stored at the individual machines, and can be recalled from the central data management device 408 when a patient submits their prescription request to confirm their identity.

[0056] Furthermore, the system 100 can perform informatics operations for quality control and inventory management. For example, the medication dispensing device 102 can know what301612543 - 15 -Atty. Docket No. UTSD.P4571WO / 1001378524drug materials are stored, and can sense when the stored drug material is running low. The information on what loose powder is inside the medication dispending device 102 can be programmed into the medication dispensing device 102 and can be monitored through alerts sent between the medication dispending device 102 and central data management device 408 of the centralized data system.

[0057] In some instances, dispensing security system components of the medication dispensing device 102 (e.g., one or more cameras, facial recognition software, passcodes, voice recognition, and so forth) can establish that only the patient to whom the medicines were prescribed can access the prescription, and that only employees of the company deploying the machines or a pharmacist has access to the loose powder material inside of the machine. For patient safety, only names and DOBs can be saved in the cloud / central data system, and these can be used only to verify the identity of the user at time of prescription fulfillment. Moreover, for restocking safety, the medication dispensing device 102 can be locked, with access only possible using a special key and / or badge provided to a pharmacy or vendor employee. Records of all access times can be recorded (e.g., at the central data management device 408 of the central data system) for monitoring and security. Moreover, the medication dispensing device 102 can have an optional biometric identification system, by which individuals can identify themselves to receive their prescription. Also, it is to be understood that any of the computational operations discussed herein can be performed at a cloud machine, such as the central data management device 408, locally at the medication dispensing device 102 itself, or both. The data of specific machines can also be accessible from the centralized data system if needed.

[0058] Additionally, in some scenarios, a patient interface on the medication dispensing device 102 (e.g., the user interface 116) can let patients enter their name, DOB, and / or a letter / number / symbol code to access their prescriptions in the absence of a QR code to scan, providing multiple authentication options. Moreover, the scanner can be used to scan IDs and / or a badge to confirm the user identity of a patient, a vendor, or a pharmacist at the time of prescription fulfillment or restocking. The system 100 can also include a camera system, similar to those at a grocery store self-checkout kiosk, which monitors the medication dispensing device 102. A real-time feed of what the camera sees can be shown at one or more interfaces, such as a display on the medication dispensing device 102 or a display remote from the medication dispensing device 102. In some instances, the user interface 116 can have a screen big enough, and / or with a high resolution, so that it is easy to see and use for all patients. The user interface 116 can have a large keyboard and / or simple buttons for completing the prescription fulfillment procedure (e.g., and to confirm identity). The user interface 116 can also have a button and / or option list to report technical issues with the301612543 - 16 -Atty. Docket No. UTSD.P4571WO / 1001378524medication dispensing device 102. For instance, example sequences might be “Report an issue with this machine” > “Label not printing” > “Please call this number to receive technical assistance” or “Report an issue with this machine” > “Prescription not found” > “Please call your provider’s office to confirm your prescription code” with relevant solution messages.

[0059] Additionally, the system 100 can include a distributor and / or vendor-facing user interface which can include a map and a log of the plurality of medication dispensing devices 102 in operation, with real-time updates on inventory and / or the number of prescriptions fulfilled. That said, patient data may not be available to vendors, but logs of times the machine is used or refilled can be available for each location for security purposes. Management teams can be able to click into any given machine and see stats for that machine, such as one or more of a time to restock, pending and / or resolved maintenance alerts, a number of times used and / or patients served, an exact contents of drug material (e.g., drug type and weight of loose powder), a temperature, and / or a battery life. Distributors may be able to access machine-specific data as needed.

[0060] In some examples, the medication dispensing device(s) 102 operating in the wireless network architecture 402 can result in various benefits, such as establishing an understanding of the medication needs of areas at the zip-code level. This system 100 can also be used to determine how many people are taking cardiovascular medication, diabetes medication, or other types of medications, which can provide a proxy of the burden of particular diseases in those regions. Furthermore, the smaller form factor of the medication dispensing device 102 can increase mobility for the medication dispensing device 102, for instance, by using the wheels 130 and / or by loading the medication dispensing device 102 into a transportation vehicle (e.g., a van). In this way, it may be possible to move the medication dispensing devices 102 to different areas based on need, or to provide door-to-door service for patients in areas with limited transit options or are unable to leave their homes, such as patients with limited mobility (e.g., elderly, who generally have high burden of disease). This improved access can benefit resource-challenged areas of the U.S. and the world.

[0061] In some scenarios, the medication dispensing device(s) 102 can include the computing device(s) 404. The computing device(s) 404 can receive and / or transmit data to and from the other components of the system 100 using one or more network(s) 122 which can include any type of network, such as the Internet, an intranet, a Virtual Private Network (VPN), a Voice over Internet Protocol (VoIP) network, an ethernet network, a network (e.g., Bluetooth®), a cellular network (e.g., 4G, 5G, LTE, etc.), satellite, combinations thereof, etc. Additionally, or alternatively, the systems 100 disclosed herein can include at least one or more server(s) 410 hosting a website or application that the computing device 404 may visit to access, control, adjust, and / or view the components of the system medication dispensing device 102. The301612543 - 17 -Atty. Docket No. UTSD.P4571WO / 1001378524website or application can receive the inputs from the computing devices 404, and can analyze the inputs to generate the outputs and / or machine control signals discussed herein. The server 410 may be a single server, a plurality of servers with each such server being a physical server or a virtual machine, or a collection of both physical servers and virtual machines. In another implementation, a cloud hosts one or more components of the central management system for controlling and / or accessing the medication dispensing device 102. The server 410 can represent an instance among large instances of application servers in a cloud computing environment, a data center, or other computing environment. The server 410 can access any of the data disclosed herein, which can be stored at one or more database(s) 412.

[0062] In some instances, the computing device(s) 404 can include a PCB and / or microcontroller integrated into the medication dispensing device 102. Additionally or alternatively, the computing device(s) 404 can include a computer, a personal computer, a desktop computer, a laptop computer, a terminal, a workstation, a cellular or mobile phone, a mobile device, a smart mobile device, a tablet, a wearable device (e.g., a smartwatch, smart glasses, a smart epidermal device, etc.), a multimedia console, a television, an Internet-of-Things (loT) device, a smart home device, another virtual reality (VR) or augmented reality (AR), a vehicle display system, and / or the like.

[0063] The computing device(s) 404 may be one or more computing systems integrated into the medication dispensing device 102 (e.g., within the housing 112). Additionally or alternatively, the computing device(s) 404 can be external from the medication dispensing device 102 while maintaining communication with the sub-assemblies of the medication dispensing device 102, such that the computing device(s) 404 can provide control signals to the sub-assemblies. The computing device 404 can be capable of executing a computer program product to execute a computer process to perform the fulfillment operations and informatics operations disclosed herein. Data and program files may be input to the computing device 404, which reads the files and executes the programs therein. Some of the elements of the computing device 404 can include one or more hardware processors 414, one or more memory devices 416, and / or one or more ports, such as input / output (IO) port(s) 418 and communication port(s) 420. Various elements of the computing device 404 may communicate with one another by way of the communication port(s) 420 and / or one or more communication buses, point-to-point communication paths, or other communication means.

[0064] The processor 414 may include, for example, a central processing unit (CPU), a microprocessor, a microcontroller, a digital signal processor (DSP), a graphics processing unit (GPU), and / or one or more internal levels of cache. There may be one or more processors 414, such that the processor 414 comprises a single central-processing unit, or a plurality of301612543 - 18 -Atty. Docket No. UTSD.P4571WO / 1001378524processing units capable of executing instructions and performing operations in parallel with each other, which can be referred to as a parallel processing environment.

[0065] The computing device 404 may be a single computer, a plurality of computers (e.g., a distributed computer), or another type of computer, such as one or more external computers made available via a cloud computing architecture. The presently described technology is optionally implemented in software stored on the data storage device(s) such as the memory device(s) 416, and / or communicated via one or more of the ports 418 / 420 to the system 100, thereby transforming the computing device 404 into a non-conventional and non-generic special purpose medication dispensing machine.

[0066] The one or more memory device(s) 414 may include any non-volatile data storage device capable of storing data generated or employed within the computing device 404, such as computer executable instructions for performing a computer process, which may include instructions of both application programs and an operating system (OS) that manages the various components of the computing device 404. The memory device(s) 414 may include, without limitation, magnetic disk drives, optical disk drives, solid state drives (SSDs), flash drives, and the like. The memory device(s) 414 may include removable data storage media, non-removable data storage media, and / or external storage devices made available via a wired or wireless network with such computer program products, including one or more database management products, web server products, application server products, and / or other additional software components. Examples of removable data storage media include Compact Disc Read-Only Memory (CD-ROM), Digital Versatile Disc Read-Only Memory (DVD-ROM), magneto-optical disks, flash drives, and the like. Examples of non-removable data storage media include internal magnetic hard disks, SSDs, and the like. The one or more memory device(s) 414 may include volatile memory (e.g., dynamic random-access memory (DRAM), static random-access memory (SRAM), etc.) and / or non-volatile memory (e.g., readonly memory (ROM), flash memory, etc.). The memory device(s) 414 which may be referred to as machine-readable media.

[0067] Moreover, It will be appreciated that machine-readable media may include tangible non-transitory medium capable of storing or encoding instructions to perform operations of the medication dispensing device 102. The machine-readable media can store computer-readable instructions for execution by a machine, and can be capable of storing or encoding data structures and modules utilized by such instructions.

[0068] In some implementations, the computing device 404 can include one or more I / O port 418 and / or I / O devices by which information is input to or output from the computing device 404. Such I / O ports 418 may include, without limitation, one or more input devices and / or301612543 - 19 -Atty. Docket No. UTSD.P4571WO / 1001378524output devices. The input devices can convert a human-generated signal, such as, human voice, physical movement, physical touch or pressure, and / or the like, into electrical signals as input data into the computing device 404 via the I / O port 418. Similarly, the output devices may convert electrical signals received from the computing device 404 via the I / O port 418 into signals that may be sensed as output by a human, such as sound, light, and / or touch. Additionally or alternatively, the output devices can provide an output as a machine control signal to the sub-assemblies of the medication dispensing device 102. The input device may be an alphanumeric input device, including alphanumeric and other keys for communicating information and / or command selections to the processor 414 via the I / O port 418. The input device may be another type of user input device including, but not limited to direction and selection control devices, such as a mouse, a trackball, cursor direction keys, a joystick, and / or a wheel; one or more sensors, such as a camera, a microphone, a positional sensor, an orientation sensor, an inertial sensor, an accelerometer; and / or a touch-sensitive display screen (“touchscreen”). The output devices may include, without limitation, a display, a touchscreen, one or more LEDs, a speaker, a tactile or haptic output device, and / or the like. In some implementations, the input device and the output device may be the same device, for example, in the case of a touchscreen. In some scenarios, the computing device 404 can include one or more GUIs for presenting the various data outputs discussed herein.

[0069] In some implementations, the communication port 420 is connected to the network 122, and the computing device 404 may receive network data useful in executing the methods and systems set out herein as well as transmitting information and network configuration changes determined thereby. Stated differently, the communication port 420 can connect the computing device 404 to one or more communication interface devices configured to transmit and / or receive information between the computing device 404 and other devices by way of one or more wired or wireless communication networks or connections, such as the network 122. Further, the communication port 420 may communicate with an antenna, satellite receiver, or other link for electromagnetic signal transmission and / or reception.

[0070] Operations of the medication dispensing device 102 and various methods disclosed herein performed by the system 100 can be embodied as data structures and / or instructions stored on the memory devices 416 and executed by the processor 414. In other words, the methods and operations disclosed may be implemented as sets of instructions that are software-readable by the computing device 404.

[0071] FIG. 5 depicts an example method 500 of dispensing medication using a medication dispensing device 102, which can be performed by any of the system(s) 100 disclosed herein.301612543 - 20 -Atty. Docket No. UTSD.P4571WO / 1001378524

[0072] In some instances, at operation 502, the method 500 can store medication at a pharmaceutical inventory system of a medication dispensing device. At operation 504, the method 500 can store a plurality of empty capsules and a plurality of empty containers at a packaging inventory system of the medication dispensing device. At operation 506, the method 500 can receive, at a user interface of the medication dispensing device, a patient identifier from a user of the medication dispensing system. At operation 506, the method 500 can fill, using a medication packing system of the medication dispensing device, one or more capsules of the plurality of empty capsules with a quantified pharmaceutical received from the pharmaceutical inventory system, resulting in one or more filled capsules, the quantified pharmaceutical being based on the patient identifier. At operation 508, the method 500 can fill, using the medication packing system, an empty container received from the packaging inventory system with the filled capsules, resulting in a filled container. At operation 510, the method 500 can provide, using a labelling system of the medication dispensing device, a personalized label corresponding to the quantified pharmaceutical.III. Polypill Formulations

[0073] Various medication formulations may be derived according to the systems and methods provided above. In some aspects, the present disclosure provides single pill formulations (POLY-HF) for heart failure. As used herein, the term “polypill” or “polypill formulation” refer to, in various aspects, a gel capsule (or other single delivery container) that contains (or encapsules) two or more medications (e.g., pills). In an aspect, the polypill comprises two or more, three or more, or four or more, individual pill formulations (i.e. , “first pill”, ‘second pill”, “third pill”, and the like) that are together encapsulated inside a single gel capsule. Each of the medications included in the polypill may be together prescribed and meant for co-administration to treat one or more diseases or conditions.

[0074] In various aspects, the single pill formulations (POLY-HF) comprise medications used in guideline-directed medical therapy (GDMT). In some cases, GDMT combines various medications, including beta blockers, renin-angiotensin-system inhibitors (RASi), sodiumglucose co-transporter 2 inhibitors (SGLT2i) and / or mineralocorticoid receptor antagonists (MRA) to ameliorate and treat heart failure with reduced ejection fraction (HFrEF). These medications act through complementary mechanisms to improve cardiac function and patient outcomes. Beta blockers reduce sympathetic nervous system activity, thereby decreasing heart rate and myocardial oxygen demand, which helps prevent disease progression and sudden cardiac death. Renin-angiotensin-system inhibitors (RASi), including ACE inhibitors, ARBs, and direct renin inhibitors, block the effects of the renin-angiotensin-aldosterone system, leading to vasodilation, reduced blood pressure, and decreased cardiac remodeling.301612543 - 21 -Atty. Docket No. UTSD.P4571WO / 1001378524Sodium-glucose co-transporter 2 inhibitors (SGLT2i) promote glycosuria and natriuresis, which can reduce cardiac preload and afterload, and have been shown to improve cardiovascular outcomes in HFrEF patients regardless of diabetic status. Mineralocorticoid receptor antagonists (MRAs) inhibit the effects of aldosterone, reducing sodium retention and myocardial fibrosis, further contributing to improved morbidity and mortality in HFrEF. Collectively, these agents target key pathophysiological pathways in heart failure, providing synergistic benefits when used in combination. However, the benefits and risks of starting all components of guideline-directed medical therapy (GDMT) concurrently, compared with sequential initiation, have not been assessed prospectively.

[0075] As shown in the Examples below, use of the polypill (e.g., POLY-HF) can feasibly overcome patient level implementation barriers, accelerate GDMT intensification, and improve cardiac function, clinical outcomes, and quality of life — even compared with a rigorously optimized usual care comparator.

[0076] Accordingly, in various aspects, a polypill formulation is provided comprising a plurality of medications in a single capsule (e.g., an inert gel capsule). In an illustrative example, the plurality of medications may comprise a beta blocker, a renin-angiotensin-system inhibitor (RASi), a sodium-glucose co-transporter 2 inhibitor (SGLT2i), and / or a mineralocorticoid receptor antagonist (MRA). In various aspects, the plurality of medications may comprise a beta blocker, a sodium-glucose co-transporter 2 inhibitor (SGLT2i), and / or a mineralocorticoid receptor antagonist (MRA).

[0077] In various aspects, a polypill formulation may comprise a beta blocker. In some aspects, the beta blocker may comprise metoprolol, bisoprolol, carvedilol, atenolol, propranolol, nebivolol, nadolol, timolol, acebutolol, pindolol, sotalol, labetalol, esmolol, betaxolol, oxprenolol, or any combination thereof. In some aspects, the beta blocker may comprise metoprolol (e.g., metoprolol succinate). In some aspects, the polypill formulation may not comprise a beta blocker.

[0078] The beta blocker (or a pharmaceutically acceptable salt thereof) is present in an amount effective to treat HFrEF, optionally selected from about 12.5 mg to 200 mg, with the final selection adjusted based on the specific active’s potency and pharmacokinetics.

[0079] In various aspects, the beta blocker may be provided in the polypill formulation at an amount of about 12.5 mg to 200 mg or about 25 to 150 mg. In various aspects, the beta blocker may be provided in the polypill formulation at a concentration of about 25 to 150 mg. In various aspects, the beta blocker (e.g., metoprolol) may be provided in the polypill formulation at an amount of about 25 mg, about 26 mg, about 27 mg, about 28 mg, about 29 mg, about 30 mg, about 31 mg, about 32 mg, about 33 mg, about 34 mg, about 35 mg, about 36 mg, about 37301612543 - 22 -Atty. Docket No. UTSD.P4571WO / 1001378524mg, about 38 mg, about 39 mg, about 40 mg, about 41 mg, about 42 mg, about 43 mg, about 44 mg, about 45 mg, about 46 mg, about 47 mg, about 48 mg, about 49 mg, about 50 mg, about 51 mg, about 52 mg, about 53 mg, about 54 mg, about 55 mg, about 56 mg, about 57 mg, about 58 mg, about 59 mg, about 60 mg, about 61 mg, about 62 mg, about 63 mg, about 64 mg, about 65 mg, about 66 mg, about 67 mg, about 68 mg, about 69 mg, about 70 mg, about 71 mg, about 72 mg, about 73 mg, about 74 mg, about 75 mg, about 76 mg, about 77 mg, about 78 mg, about 79 mg, about 80 mg, about 81 mg, about 82 mg, about 83 mg, about 84 mg, about 85 mg, about 86 mg, about 87 mg, about 88 mg, about 89 mg, about 90 mg, about 91 mg, about 92 mg, about 93 mg, about 94 mg, about 95 mg, about 96 mg, about 97 mg, about 98 mg, about 99 mg, about 100 mg, about 101 mg, about 102 mg, about 103 mg, about 104 mg, about 105 mg, about 106 mg, about 107 mg, about 108 mg, about 109 mg, about 110 mg, about 111 mg, about 112 mg, about 113 mg, about 114 mg, about 115 mg, about 116 mg, about 117 mg, about 118 mg, about 119 mg, about 120 mg, about 121 mg, about 122 mg, about 123 mg, about 124 mg, about 125 mg, about 126 mg, about 127 mg, about 128 mg, about 129 mg, about 130 mg, about 131 mg, about 132 mg, about 133 mg, about 134 mg, about 135 mg, about 136 mg, about 137 mg, about 138 mg, about 139 mg, about 140 mg, about 141 mg, about 142 mg, about 143 mg, about 144 mg, about 145 mg, about 146 mg, about 147 mg, about 148 mg, about 149 me , or about 150 mg. In various aspects, the beta blocker (e.g., metoprolol) may be provided in the polypill formulation at a concentration of 25 mg. In various aspects, the beta blocker (e.g., metoprolol) may be provided in the polypill formulation at a concentration of 50 mg. In various aspects, the beta blocker (e.g., metoprolol) may be provided in the polypill formulation at a concentration of 100 mg. In various aspects, the beta blocker (e.g., metoprolol) may be provided in the polypill formulation at a concentration of 150 mg.

[0080] In various aspects, a polypill formulation may comprise a renin-angiotensin-system (RAS) inhibitor. In some aspects, the RAS inhibitor may comprise an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB). Exemplary ACE inhibitors that may be used in the present formulations include, but are not limited to: enalapril, lisinopril, captopril, ramipril, benazepril, quinapril, fosinopril, perindopril, trandolapril, or combinations thereof. Exemplary ARBs that may be used in the present formulations include losartan, valsartan, candesartan, irbesartan, telmisartan, olmesartan, eprosartan, valsartan. In some aspects, the RASi may comprise a direct renin inhibitor such as aliskiren. In some aspects, the polypill formulation does not comprise a RAS inhibitor.

[0081] The RAS inhibitor (or a pharmaceutically acceptable salt thereof) is present in an amount effective to treat HFrEF, optionally selected from about 1 to 200 mg for ACE inhibitors301612543 - 23 -Atty. Docket No. UTSD.P4571WO / 1001378524and about 4 to 400 mg for ARBs, with the final selection adjusted based on the specific active’s potency and pharmacokinetics.

[0082] In various aspects, the RAS inhibitor (e.g., an ACE inhibitor) is present in the polypill formulation at an amount of about 1 to 200 mg, about 1 to 100 mg, about 1 to 50 mg, or about 2.5 to 40 mg. In various aspects, the RAS inhibitor (e.g., an ACE inhibitor such as enalapril) is present in the polypill formulation at an amount of about 2.5 to 40 mg. In various aspects, the RAS inhibitor (e.g., an ACE inhibitor such as lisinopril) is present in the polypill formulation at an amount of about 5 to 40 mg. In various aspects, the RAS inhibitor (e.g., an ACE inhibitor such as lisinopril) is present in the polypill formulation at an amount of about 1.25 to 10 mg. In various aspects, the RAS inhibitor (e.g., an ACE inhibitor such as quinapril / fosinopril / benazepril) is present in the polypill formulation at an amount of about 5 to 40 mg. In various aspects, the RAS inhibitor (e.g., an ACE inhibitor such as perindopril) is present in the polypill formulation at an amount of about 2 to 8 mg. In various aspects, the RAS inhibitor (e.g., an ACE inhibitor such as trandolapril) is present in the polypill formulation at an amount of about 1-4 mg. In various aspects, the RAS inhibitor (e.g., an ACE inhibitor such as captopril) is present in the polypill formulation at an amount of about 6.25 to 50 mg per dose. In various aspects, the polypill formulation comprises a RAS inhibitor (e.g., an ACE inhibitor) at an amount of about 1 mg, about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2 mg, about 2.25 mg, about 2.5 mg, about 2.75 mg, about 3 mg, about 3.25 mg, about 3.5 mg, about 3.75 mg, about 4 mg, about 4.25 mg, about 4.5 mg, about 4.75 mg, about 5 mg, about 5.25 mg, about 5.5 mg, about 5.75 mg, about 6 mg, about 6.25 mg, about 6.5 mg, about 6.75 mg, about 7 mg, about 7.25 mg, about 7.5 mg, about 7.75 mg, about 8 mg, about 8.25 mg, about 8.5 mg, about 8.75 mg, about 9 mg, about 9.25 mg, about 9.5 mg, about 9.75 mg, or about 10 mg. In various aspects, the polypill formulation comprises a RAS inhibitor (e.g., an ACE inhibitor) at an amount of about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, or about 100 mg.

[0083] In various aspects, the RAS inhibitor (e.g., an ARB) is present at an amount of about 4 to 800 mg, about 4 to 400 mg, about 10 to 400 mg, or about 25 to 320 mg. In various aspects, the RAS inhibitor (e.g., an ARB such as losartan) is present at an amount of about 25 to 150 mg. In various aspects, the RAS inhibitor (e.g., an ARB such as candesartan) is present at an amount of about 4 to 32 mg. In various aspects, the RAS inhibitor (e.g., an ARB such as valsartan) is present at an amount of about 40 to 320 mg. In various aspects, the RAS inhibitor (e.g., an ARB such as irbesartan) is present at an amount of about 75 to 300 mg. In various aspects, the RAS inhibitor (e.g., an ARB such as telmisartan) is present at an amount of about 20 to 80 mg. In various aspects, the RAS inhibitor (e.g., an ARB such as olmesartan) is present at an amount of about 10 to 40 mg. In various aspects, the RAS inhibitor (e.g., an301612543 - 24 -Atty. Docket No. UTSD.P4571WO / 1001378524ARB such as eprosartan) is present at an amount of about 400 to 800 mg. the In various aspects, the RAS inhibitor (e.g., an ARB) is present at an amount of about 4 mg, about 5 mg about 10 mg, about 20 mg, about 25 mg, about 30 mg, about 32 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 75 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 770 mg, about 780 mg, about 790 mg, or about 800 mg. In various aspects, the RAS inhibitor (e.g., an ARB) is present at an amount of about 25 mg, 50 mg, 100 mg, 150 mg, 160 mg, or 320 mg.

[0084] In various aspects, a polypill formulation may comprise a sodium-glucose cotransporter 2 inhibitor (SGLT2i). In various aspects, the SGLT2i may comprise empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, ipragliflozin, tofogliflozin, luseogliflozin, or sotagliflozin, or combinations thereof. In various aspects, the SGLT2i may comprise empagliflozin. In some aspects, the polypill formulation may not comprise a SGLT2L

[0085] In various aspects, the SGLT2 inhibitor (or a pharmaceutically acceptable salt thereof) is present in the polypill in an amount effective to treat HFrEF, optionally selected from about 1-50 mg for high-potency SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) or about 50-500 mg for agents for lower-potency SGLT1 / SGLT2 agents (e.g., sotagliflozin), with the final selection adjusted based on the specific active’s potency and pharmacokinetics.

[0086] In some aspects, the SGLT2i may be present in the polypill at an amount of about 1 to 50 mg, about 5 to 25 mg, about 8 to 15 mg, or about 9 to 11 mg. In some aspects, the SGTL2i (e.g., empagliflozin, dapagliflozin) may be present in the polypill at a dose of about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, about 25 mg, about 26 mg, about 27 mg, about 28 mg, about 29 mg, about 30 mg, about 31 mg, about 32 mg, about 33 mg, about 34 mg, about 35 mg, about 36 mg, about 37 mg, about 38 mg, about 39 mg, about 40 mg, about 41 mg, about 42 mg, about301612543 - 25 -Atty. Docket No. UTSD.P4571WO / 100137852443 mg, about 44 mg, about 45 mg, about 46 mg, about 47 mg, about 48 mg, about 49 mg, about 50 mg. In various aspects, the SGTL2i (e.g., empagliflozin, dapagliflozin) may be present in the polypill at a dose of about 5 mg, about 10 mg, about 12.5 mg, about 15 mg, about 20 mg, or about 25 mg. In various aspects, the SGTL2i (e.g., empagliflozin, dapagliflozin) may be present in the polypill at a dose of 10 mg.

[0087] In some aspects, the the SGLT2i (e.g., a SGLT1 / SGLT2 agent such as sotagliflozin), may be present in the polypill at an amount of about 100 to 500 mg, about 150 to 450 mg, about 200 to 400mg. In some aspects, the SGLT2i (e.g., a SGLT1 / SGLT2 agent such as sotagliflozin), may be present in the polypill at an amount of about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, about 500 mg. For example, in various aspects, the SGLT2i (e.g., a SGLT 1 / SGLT2 agent such as sotagliflozin), may be present in the polypill at a dose of about 200 mg, about 300 mg, or about 400 mg.

[0088] In various aspects, a polypill formulation may comprise a mineralocorticoid receptor antagonist (MRA). In various aspects, the MRA may comprise spironolactone, eplerenone, finerenone, canrenone, esaxerenone, apararenone, ocedurenone, or combinations thereof. In various aspects, the MRA may comprise spironolactone. In some aspects, the polypill formulation may not comprise a MRA.

[0089] In various aspects, the mineralocorticoid receptor antagonist (MRA) (or a pharmaceutically acceptable salt thereof) may be present in the polypill in an amount effective to treat HFrEF, optionally selected from about 5 to 100 mg for steroidal MRAs (e.g., spironolactone, eplerenone) or about 2.5 to 40 mg for non-steroidal MRAs (e.g., finerenone, esaxerenone, apararenone, ocedurenone), with the final selection adjusted based on the specific active’s potency and pharmacokinetics.

[0090] In various aspects, the mineralocorticoid receptor antagonist (MRA) (e.g., a steroidal MRA such as spironolactone or eplerenone) may be present in the polypill in an amount of about 5 to 100 mg, about 12.5 to 50 mg, or about 25 to 50 mg. In various aspects, the mineralocorticoid receptor antagonist (MRA) (e.g., a steroidal MRA such as spironolactone or eplerenone) may be present in the polypill in an amount of about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, or about 100 mg. In some aspects, the mineralocorticoid receptor antagonist (MRA) (e.g., a steroidal MRA such as spironolactone or eplerenone) may be present in the polypill in an amount of about about 12.5 mg, about 13301612543 - 26 -Atty. Docket No. UTSD.P4571WO / 1001378524mg, about 13.5 mg, about 14 mg, about 14.5 mg, about 15 mg, about 15.5 mg, about 16 mg, about 16.5 mg, about 17 mg, about 17.5 mg, about 18 mg, about 18.5 mg, about 19 mg, about 19.5 mg, about 20 mg, about 20.5 mg, about 21 mg, about 21.5 mg, about 22 mg, about 22.5 mg, about 23 mg, about 23.5 mg, about 24 mg, about 24.5 mg, about 25 mg, about 25.5 mg, about 26 mg, about 26.5 mg, about 27 mg, about 27.5 mg, about 28 mg, about 28.5 mg, about 29 mg, about 29.5 mg, about 30 mg, about 30.5 mg, about 31 mg, about 31.5 mg, about 32 mg, about 32.5 mg, about 33 mg, about 33.5 mg, about 34 mg, about 34.5 mg, about 35 mg, about 35.5 mg, about 36 mg, about 36.5 mg, about 37 mg, about 37.5 mg, about 38 mg, about 38.5 mg, about 39 mg, about 39.5 mg, about 40 mg, about 40.5 mg, about 41 mg, about 41.5 mg, about 42 mg, about 42.5 mg, about 43 mg, about 43.5 mg, about 44 mg, about 44.5 mg, about 45 mg, about 45.5 mg, about 46 mg, about 46.5 mg, about 47 mg, about 47.5 mg, about 48 mg, about 48.5 mg, about 49 mg, about 49.5 mg, or about 50 mg. In various aspects, the mineralocorticoid receptor antagonist (MRA) (e.g., spironolactone) may be present in the polypill in an amount of about 12.5 mg, about 25 mg, or about 25 mg. In various aspects, the mineralocorticoid receptor antagonist (MRA) (e.g., spironolactone) may be present in the polypill in an amount of about 12.5 mg. In various aspects, the mineralocorticoid receptor antagonist (MRA) (e.g., eplerenone) may be present in the polypill in an amount of about 25 mg or about 50 mg. In various aspects, the mineralocorticoid receptor antagonist (MRA) (e.g., eplerenone) may be present in the polypill in an amount of about 25 mg. In various aspects, the mineralocorticoid receptor antagonist (MRA) (e.g., eplerenone) may be present in the polypill in an amount of about 50 mg.

[0091] In various aspects, the mineralocorticoid receptor antagonist (MRA) (e.g., a nonsteroidal MRA such as finerenone, esaxerenone, apararenone, ocedurenone) may be present in the polypill in an amount of about 2.5 to 40 mg, about 5 to 30mg, or about 10 to 20mg. In various aspects, the mineralocorticoid receptor antagonist (MRA) (e.g., a non-steroidal MRA such as finerenone, esaxerenone, apararenone, ocedurenone) may be present in the polypill in an amount of about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 4.5 mg, about 5 mg, about 5.5 mg, about 6 mg, about 6.5 mg, about 7 mg, about 7.5 mg, about 8 mg, about 8.5 mg, about9 mg, about9.5 mg, about 10 mg, about 10.5 mg, about 11 mg, about 11.5 mg, about 12 mg, about 12.5 mg, about 13 mg, about 13.5 mg, about 14 mg, about 14.5 mg, about 15 mg, about 15.5 mg, about 16 mg, about 16.5 mg, about 17 mg, about 17.5 mg, about 18 mg, about 18.5 mg, about 19 mg, about 19.5 mg, about 20 mg, about 20.5 mg, about 21 mg, about 21.5 mg, about 22 mg, about 22.5 mg, about 23 mg, about 23.5 mg, about 24 mg, about 24.5 mg, about 25 mg, about 25.5 mg, about 26 mg, about 26.5 mg, about 27 mg, about 27.5 mg, about 28 mg, about 28.5 mg, about 29 mg, about 29.5 mg, about 30 mg, about 30.5 mg, about 31 mg, about 31.5 mg, about 32 mg, about 32.5 mg, about 33 mg, about 33.5 mg, about301612543 - 27 -Atty. Docket No. UTSD.P4571WO / 100137852434 mg, about 34.5 mg, about 35 mg, about 35.5 mg, about 36 mg, about 36.5 mg, about 37 mg, about 37.5 mg, about 38 mg, about 38.5 mg, about 39 mg, about 39.5 mg, or about 40 mg. In various aspects, the mineralocorticoid receptor antagonist (MRA) (e.g., a non-steroidal MRA such as finerenone, esaxerenone, apararenone, ocedurenone) may be present in the polypill in an amount of about 10 mg or about 20 mg.

[0092] In various aspects, a polypill formulation is provided comprising: a first pill comprising a beta blocker, a second pill comprising a sodium-glucose co-transporter 2 inhibitor (SGLT2i), and a third pill comprising a mineralocorticoid receptor antagonist (MRA), and a gel capsule encapsulating the first, second, and third pills. In aspects, the first pill comprises metoprolol succinate, the second pill comprises empagliflozin, and the third pill comprises spironolactone. In aspects, the first pill comprises 25 mg, 50 mg, 100 mg, or 150 mg metoprolol succinate, the second pill comprises 10 mg empagliflozin, and the third pill comprises 12.5 mg spironolactone. In various aspects, the first pill comprises 25 mg of metoprolol succinate, the second pill comprises 10 mg of empagliflozin, and the third pill comprises 12.5 mg of spironolactone. In various aspects, the first pill comprises 50 mg of metoprolol succinate, the second pill comprises 10 mg of empagliflozin, and the third pill comprises 12.5 mg of spironolactone. In various aspects, the first pill comprises 100 mg of metoprolol succinate, the second pill comprises 10 mg of empagliflozin, and the third pill comprises 12.5 mg of spironolactone. In various aspects, the first pill comprises 150 mg of metoprolol succinate, the second pill comprises 10 mg of empagliflozin, and the third pill comprises 12.5 mg of spironolactone.

[0093] The polypill formulations may further comprise other pharmaceutically appropriate excipients or carriers, especially excipients or carriers appropriate for oral administration. In various aspects, excipients or carriers appropriate for oral administration may comprise fillers or diluents such as lactose, microcrystalline cellulose, mannitol, dicalcium phosphate, and starch; binders such as povidone (PVP), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), pregelatinized starch, and acacia; disintegrants such as croscarmellose sodium, sodium starch glycolate, crospovidone, and starch; lubricants such as magnesium stearate, stearic acid, sodium stearyl fumarate, and talc; glidants such as colloidal silicon dioxide and talc; coating agents or film formers such as HPMC, methacrylic acid copolymers (e.g., Eudragit), cellulose acetate, and polyvinyl alcohol; plasticizers such as polyethylene glycol (PEG), triethyl citrate, and dibutyl sebacate; surfactants or wetting agents such as sodium lauryl sulfate, polysorbate 80, and poloxamers; solubilizers such as cyclodextrins (e.g., - cyclodextrin, hydroxypropyl-p-cyclodextrin), PEG, and povidone; matrix formers or sustained-release agents such as HPMC, ethylcellulose, xanthan gum, and Carbopol; sweeteners or flavoring agents such as sucralose, aspartame, saccharin, sorbitol,301612543 - 28 -Atty. Docket No. UTSD.P4571WO / 1001378524and flavorings (e.g., peppermint); coloring agents or opacifiers such as titanium dioxide, iron oxides, and FD&C dyes; antioxidants such as butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), and ascorbyl palmitate; preservatives such as parabens (e.g., methylparaben, propylparaben) and benzoic acid or sodium benzoate; capsule or shell materials such as gelatin, HPMC, pullulan, and starch-based shells; liquids for oral solutions or suspensions such as purified water, glycerin, propylene glycol, and medium-chain triglycerides (e.g., for softgels); and suspending or thickening agents such as xanthan gum, sodium carboxymethyl cellulose (NaCMC), and microcrystalline cellulose / sodium CMC blends (e.g., Avicel RC / CL).

[0094] The polypill formulations may further comprise one or more other active pharmaceutical ingredients.IV. Methods of Treating

[0095] The present disclosure is further directed to methods of treating a disease or condition using a polypill formulation described herein. The polypill formulation may be prepared using the medication dispensing system described in Section I and / or may be any polypill formulation described in Section II. As shown in the Examples below, it has been advantageously shown that administering therapies for certain conditions that require multiple medications using a polypill formulation leads to better compliance and improved clinical outcomes.

[0096] In various aspects, the disease or condition may be a cardiovascular disease or condition. In further aspects, the disease or condition comprises heart failure. In further aspects, the disease or condition comprises heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), acute decompensated heart failure, chronic heart failure, right-sided heart failure, left-sided heart failure, high-output heart failure, low-output heart failure, or combinations thereof. In various aspects, the disease or condition comprises heart failure with reduced ejection fraction.

[0097] In various aspects, the methods of treating the disease or condition may comprise administering the polypill formulation disclosed herein one or more times a day to a subject in need thereof. In some aspects In some aspects, administering the polypill formulation comprises a once-daily regimen, for example, administering one capsule in the morning; in some aspects, administering the polypill formulation comprises a twice-daily regimen, for example, administering one capsule in the morning and one capsule in the evening approximately 12 hours apart; in some aspects, administering the polypill formulation comprises a three-times-daily regimen, for example, administering one capsule in the301612543 - 29 -Atty. Docket No. UTSD.P4571WO / 1001378524morning, one capsule in the afternoon, and one capsule in the evening at approximately 8-hour intervals. In some aspects, administering the polypill formulation comprises a titration schedule transitioning from once-daily to twice-daily dosing over 1-4 weeks based on tolerability. In some aspects, administering the polypill formulation comprises a patient-tailored schedule coordinated with meals (e.g., morning with or without food, evening with or without food) or bedtime to optimize tolerability and adherence; and in some aspects, administering the polypill formulation comprises dose splitting across morning and evening capsules to distribute individual active components according to pharmacokinetic, pharmacodynamic, or safety considerations.

[0098] In some aspects, the methods of treating the disease or condition may comprise administering the polypill formulation disclosed herein and administering one or more additional active pharmaceutical ingredients that are not in the polypill formulation.

[0099] An “individual” or “subject,” as used interchangeably herein, is a mammal. In certain aspects, the individual or subject is a human.

[0100] It is to be understood that the specific order or hierarchy of steps in the methods depicted throughout this disclosure are instances of example approaches and can be rearranged while remaining within the disclosed subject matter. For instance, any of the operations discussed throughout this disclosure may be omitted, repeated, performed in parallel, performed in a different order, and / or combined with any other of the operations discussed throughout this disclosure.

[0101] While the present disclosure has been described with reference to various implementations, it will be understood that these implementations are illustrative and that the scope of the present disclosure is not limited to them. Many variations, modifications, additions, and improvements are possible. More generally, implementations in accordance with the present disclosure have been described in the context of particular implementations. Functionality may be separated or combined differently in various implementations of the disclosure or described with different terminology. For example, any component disclosed herein can be combined with any other component disclosed herein. These and other variations, modifications, additions, and improvements may fall within the scope of the disclosure as defined in the claims that follow.EXAMPLESExample 1: Introduction to Examples

[0102] Heart failure (HF) represents a major public health challenge, affecting more than 6 million Americans with 5-year mortality rates approaching 50%. Guideline-directed medical301612543 - 30 -Atty. Docket No. UTSD.P4571WO / 1001378524therapy (GDMT) improves clinical outcomes among patients with HF with reduced ejection fraction (HFrEF). Contemporary GDMT involves the use of four medication classes: beta blockers, renin-angiotensin-system inhibitors (RASi), sodium-glucose co-transporter 2 inhibitors (SGLT2i), and mineralocorticoid receptor antagonists (MRAs). The use of these medications in combination reduces all-cause mortality by approximately 50% compared with conventional two-drug therapy. Nonetheless, overall utilization of GDMT is low. Only 15% of patients hospitalized with HFrEF receive any dose of quadruple GDMT, and uptitration to optimal doses is even more rare. Recent evidence from the STRONG-HF trial underscores the clinical relevance of these implementation gaps. In that trial, achievement of optimal GDMT following HF hospitalization was associated with a 34% lower risk of all-cause death or HF readmission.

[0103] Suboptimal utilization of GDMT stems from both provider-level and patient-level barriers. Provider-level factors include therapeutic inertia and concerns about adverse effects. Patient-level barriers include polypharmacy burden, complex dosing regimens, and high medication costs. Several implementation strategies have been tested to improve use of GDMT, primarily targeting provider-level barriers through virtual consultations, clinician education, dedicated GDMT clinics, and feedback reports with continuous quality improvement. These interventions have demonstrated heterogeneous effects on GDMT uptake, with some having only a modest increase and others showing no improvement. Furthermore, data regarding the impact of such interventions on clinical outcomes are lacking. Lastly, most tested interventions do not adequately address patient-level barriers to GDMT, highlighting the need for new approaches.

[0104] The “polypill” combines multiple medications into a single pill and may be a promising strategy for improving utilization of evidence-based medications. It has been evaluated for the primary or secondary prevention of ASCVD but not in individuals with HF. Reasons that single pill therapies have not been examined previously in HF might include concerns about reduced flexibility for dosing individual medications; the perceived risks of all-or-none treatment; and increased side effect profiles. Further, the benefits and risks of starting all components of GDMT concurrently, compared with sequential initiation, have not been assessed prospectively.

[0105] The following Examples describe a randomized controlled trial to evaluate whether a polypill-based strategy leads to improved left ventricular function compared with enhanced usual care in patients with HFrEF.

[0106] It was surprisingly found in this randomized trial, that a polypill strategy for patients with HFrEF improved cardiac function, quality of life, and clinical outcomes compared with301612543 - 31 -Atty. Docket No. UTSD.P4571WO / 1001378524enhanced usual care. The polypill approach facilitated improved utilization and adherence to GDMT by addressing structural barriers related to prescription complexity and pill burden. These findings support the use of polypill strategies to optimize GDMT implementation in HFrEF.Example 2: Study Population

[0107] Between 2021 and 2025, 475 patients who met eligibility criteria for the study were identified (FIG. 6). From this group, 262 patients agreed to participate in a screening examination, and 212 were randomized to either polypill therapy (n = 108) or enhanced usual care (n = 104). A total of 190 participants (90%) attended all study visits, with similar completion rates in the polypill arm (88%) and enhanced usual care arms (91%). Three participants had recovered systolic function (LVEF > 55%) by the time of the first (baseline) MRI and were excluded from the primary analyses. A follow-up MRI at 6 months was obtained for 187 participants (95 in the polypill arm and 92 in the enhanced usual care arm).

[0108] Baseline characteristics were similar between treatment groups (Table 1). The median age was 53 years, 78% were male, 54% were Black, and 33% were Hispanic. A total of 68% were uninsured or relied on county indigent health programs. Approximately half (53%) presented with new-onset (acute) HF, and 79% had non-ischemic cardiomyopathy. Median baseline LVEF by cardiac MRI was 26% (IQR: 19.6-34.2).Table 1: Baseline characteristics by study group301612543 - 32 -Atty. Docket No. UTSD.P4571WO / 1001378524301612543 - 33 -Atty. Docket No. UTSD.P4571WO / 1001378524> >Example 3: Primary and Secondary Endpoints

[0109] At 6 months, the primary endpoint, LVEF by MRI, was higher in individuals randomized to the polypill compared with those randomized to enhanced usual care (40% vs 37%; adjusted between-group difference, 3.4 percentage points; 95% Cl, 0.41 to 6.34; p=0.026;Table 2). Similar findings were noted in secondary analyses utilizing echocardiographic LVEF (45% vs 42%; difference, 3.4 percentage points, 95% Cl, 0.52 to 6.18; p=0.021).Table 2: Treatment effects of polypill vs enhanced usual care among participants with heart failure with reduced ejection fraction.<301612543 - 34 -Atty. Docket No. UTSD.P4571WO / 1001378524<>> >

[0110] Individuals treated with the polypill also had a reduction in clinical events, with rate of HF hospitalization or ED visit for HF of 37.1 events per 100 person-years, versus 85.8 events per 100 person-years for individuals in the enhanced usual care arm (adjusted rate ratio, 0.40, 95% Cl, 0.23 to 0.70; p=0.001). A similar pattern of treatment effects was observed in time-to-event analyses for HF events or mortality (adjusted hazard ratio, 0.41 ; 95% Cl, 0.20 to 0.83; p=0.001; FIG. 7A). The polypill strategy was also associated with a lower rate of all-cause hospitalization (adjusted rate ratio, 0.47; 95% Cl, 0.29-0.76; p = 0.002).

[0111] The KCCQ-OSS at 6 months was 71.9 (95% Cl, 60.5 to 83.3) in the polypill arm compared with 63.2 (95% Cl, 51.8 to 74.6) in the enhanced usual care arm (adjusted difference, 8.7 points; 95% Cl, 2.8 to 14.6; p=0.004; FIG. 7B). No significant differences were observed in performance on the 6MWD or levels of NT-proBNP between the two arms.

[0112] In a win-ratio analysis of the prespecified composite outcome, the polypill strategy was superior to enhanced usual care, with a win ratio of 1.72 (95% Cl, 1.65 to 1.80; p<0.001) (Table 2, FIG. 7C). The treatment benefit was driven primarily by improvements in quality of life (>5-point improvement in KCCQ-OSS: 32.9% wins vs 15.6% losses) and in total HF hospitalizations or ED visits for HF (8.9% wins vs 5.1% losses).301612543 - 35 -Atty. Docket No. UTSD.P4571WO / 1001378524

[0113] In the polypill arm, 79% of participants were fully adherent (detectable serum levels of all tested medications) compared with 54% in the enhanced usual care arm (adjusted odds ratio, 4.15; 95% Cl, 2.04 to 8.45; p<0.001).

[0114] The treatment effect for the primary endpoint appeared to be similar across prespecified subgroups, including race, sex, ethnicity, and HF chronicity (FIG. 9).Example 4: Sensitivity analyses

[0115] In an analysis of the primary endpoint that included the 25 participants lacking followup MRI data, the difference in LVEF at 6 months remained significant (difference, 3.1%; 95% Cl, 0.14 to 6.15; p = 0.04). Similarly, the inclusion of the three participants with a baseline recovered EF did not alter the findings (difference, 3.2%, 95% Cl, 0.1 to 6.4; p = 0.04). Excluding participants with suboptimal short-axis images at baseline or follow-up also yielded similar results (LVEF difference, 3.1%, 95% Cl, 0.05 to 6.21; p=0.047; Table 3).Table 3. Sensitivity analyses for the primary outcome.Example 5: Utilization of GDMT By Study Group

[0116] Utilization of individual GDMT classes by study group over time is illustrated in FIGS.10A-10D. At baseline, the utilization of quadruple GDMT at any dose was similar between groups (44% in the polypill arm versus 52% in the enhanced usual care arm). Following randomization, quadruple GDMT utilization increased overtime in both arms, with the largest gains occurring within the first month (96% in the polypill arm versus 71% in enhanced usual care at 1 month). The polypill arm achieved and maintained significantly higher quadruple GDMT utilization at any dose at all post-randomization timepoints, and at 6 months, participants in the polypill arm had 16-fold higher odds of receiving quadruple GDMT compared to enhanced usual care (aOR 17.0, 95% Cl 3.57, 81.1, p<0.001, FIG. 8). A similar pattern of results was noted for quadruple GDMT utilization at the optimal doses. While301612543 - 36 -Atty. Docket No. UTSD.P4571WO / 1001378524baseline rates were low and comparable between groups (4.6% versus 5.8%), the polypill arm achieved and maintained significantly higher optimal GDMT utilization at all postrandomization timepoints, with 70.5% at 6 months compared with 42% in enhanced usual care (adjusted odds ratio, 3.86; 95% Cl, 2.0 to 7.45; p<0.001). Similarly, the mHFC score demonstrated consistently greater improvement in the polypill arm at all post-randomization time points, increasing from a mean of 62.0 at baseline to 91.7 at 6 months, compared with an increase from 65.7 to 80.8 in the enhanced usual care arm (p < 0.001).Example 6: Safety Outcomes

[0117] Serious adverse events were less frequent in the polypill arm compared with enhanced usual care. One death occurred in each arm (Table 4). Physician-directed treatment discontinuations were infrequent. The polypill was discontinued in 1 participant (0.9%) in the polypill arm, and 2 (1.8%) participants also had their RASi discontinued (Table 5). In the enhanced usual care arm, physician / care team-directed discontinuations included betablockers in 1 participant (1.0%), RASi in 3 (2.9%), SGLT2i in 2 (1.9%), and MRA therapy in 1 (1.0%). The number of temporary treatment interruptions with successful rechallenge was similar between groups (Table 5).Table 4. Adverse events across the study groups> > < > >301612543 - 37 -Atty. Docket No. UTSD.P4571WO / 1001378524Table 5. Care team or study team directed treatment pauses and discontinuation across study groupsExample 7: MethodsTrial Design

[0118] D The POLY-HF trial was a two-center, open-label, randomized controlled trial funded by the National Institute on Minority Health and Health Disparities. It was conducted between November 2021 and October 2025. The trial protocol was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center and monitored by an independent data safety and monitoring board. Details of the trial design have previously been published, and the trial was registered on clinicaltrials.gov (NCT04633005).Setting and Trial Participants

[0119] The study was conducted at two hospitals in Dallas, Texas: Parkland Hospital, a safety-net county hospital serving predominantly uninsured patients, and Clements University Hospital at UT Southwestern Medical Center. Participants were recruited during hospitalizations for HF or at outpatient cardiology visits. Eligibility requirements included age301612543 - 38 -Atty. Docket No. UTSD.P4571WO / 1001378524>18 years, symptomatic HFrEF with LVEF by screening echocardiogram < 40%, and not receiving the target dose of quadruple GDMT. Key exclusion criteria included serum creatinine >2.5 mg / dL for men or >2.0 mg / dL for women, contraindications to HFrEF GDMT, or inability to undergo cardiac magnetic resonance imaging (OMR). All participants provided written informed consent.Randomization and Treatment Intervention

[0120] Participants were randomly assigned 1:1 to polypill-based therapy or enhanced usual care using block randomization stratified by acute versus chronic HF status and Black versus non-Black race. Polypills were created by over-encapsulating the following individual medications in an inert gel capsule: empagliflozin 10 mg, spironolactone 12.5 mg, metoprolol succinate (25, 50, 100, or 150 mg). The Food and Drug Administration provided an Investigational New Drug exemption for the polypills used in this study. The polypill was assembled by an external pharmacy (Pharmacy Solutions, Arlington, TX).

[0121] The rationale for polypill dosing and components has been detailed previously. Dose selection was influenced by data from BIOSTAT-CHF, which demonstrated that patients achieving at least 50% of target doses had outcomes similar to those reaching 100% of target doses. Spironolactone was included at a 12.5 mg dose based on evidence demonstrating effective aldosterone blockade and low risk of hyperkalemia, similar to placebo. Empagliflozin was included at 10 mg, consistent with EMPEROR-Reduced. Four doses of metoprolol succinate were available, to allow uptitration to the most commonly utilized doses.

[0122] At randomization, participants assigned to the polypill arm were switched from an individual beta-blocker, MRA, and / or SGLT2i to a polypill containing these therapies. Participants received an initial 30-day polypill prescription at randomization. Participants continued RASi therapy separately. RASi were not included in the polypill to allow use of sacubitril / valsartan, which is dosed twice daily and thus not well-suited for inclusion in a once-daily polypill. In the enhanced usual care arm, the study team collaborated with participants' primary care or cardiology providers to initiate and optimize individual GDMT components. Patients were provided beta-blockers, MRAs, and SGLT2i medications at no cost, to minimize differences in the cost of GDMT between study arms.Follow-up and Assessments

[0123] Participants attended in-person visits at months 1, 3, and 6. Participants received 30-day medication refills until titration to maximally tolerated doses of GDMT was achieved; then, 60- or 90-day supplies were dispensed. At the 6-month visit, participants in the polypill arm were transitioned to equivalent doses of individual GDMT components to ensure continuity of care after trial completion. At each visit, vital signs and blood samples were obtained for301612543 - 39 -Atty. Docket No. UTSD.P4571WO / 1001378524measurement of the metabolic panel and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ), and functional capacity was measured using the 6-minute walk test. Medication adherence was assessed using therapeutic drug monitoring (TDM) with quantitative liquid chromatography-tandem mass spectrometry (LC-MS / MS) to measure serum levels of metoprolol and spironolactone, as previously reported.

[0124] Cardiac magnetic resonance imaging (CMR) was performed at baseline and 6 months on a 3T system (Achieva; Philips Medical Systems, Best, Netherlands) at the Advanced Imaging Research Center, LIT Southwestern Medical Center. Short-axis imaging was used for primary LVEF analysis at baseline and follow-up. In participants with suboptimal short-axis images at either baseline or follow-up (n=10), long-axis images were used for EF assessment. Images were analyzed in a core laboratory using standardized software (CVI42, Circle Cardiovascular Imaging, Calgary, Canada) by two cardiologists with advanced training and board certification in CMR (KY and VZ) who were blinded to treatment assignment. Echocardiography was performed according to standard protocols in a core lab at LIT Southwestern at baseline and 6 months. In a subset of participants who did not undergo protocol-specified baseline echocardiography, clinical screening echocardiograms obtained at index hospitalization were utilized for LVEF assessment.Outcomes

[0125] The primary outcome was LVEF at 6 months assessed by CMR. Pre-specified secondary outcomes included the following: HF hospitalization or all-cause mortality, HF hospitalization or emergency department visit for worsened HF, LVEF by echocardiography, quality of life (KCCQ Overall Summary Score [KCCQ-OSS]), exercise capacity (6-minute walk distance; 6MWD), adherence (TDM), and NT-proBNP. Also calculated was a win-ratio-based composite endpoint that included the following outcomes in hierarchical order: all-cause mortality, >5-point improvement in KCCQ-OSS, total HF hospitalizations or emergency department visits for HF, >5% improvement in LVEF from baseline to 6 months by CMR, and adherence by TDM. For TDM, participants were classified as adherent if they had detectable serum levels of all tested medications and non-adherent if any tested medication was undetectable.

[0126] Use of GDMT was characterized in several ways: quadruple GDMT utilization (prescription of all four GDMT classes at any dose); optimal GDMT utilization (prescription of all four GDMT classes with beta-blocker >50% of target doses, ACEi / ARB at >50% of target dose or any dose ofARNi, any dose of SGLT2i, and any dose of MRA), and the modified Heart Failure Collaboratory (HFC) score. Safety outcomes included serious adverse events,301612543 - 40 -Atty. Docket No. UTSD.P4571WO / 1001378524hyperkalemia (serum potassium >5.5 mmol / L and > 6.0 mmol / L), systolic blood pressure < 90 mm Hg, all-cause hospitalizations, or death. A complete list of all prespecified outcomes is provided in the study design manuscript.Statistical Analysis

[0127] It was estimated that a total sample size of 175 participants would provide >90% power to detect a 5-percentage point difference in LVEF between treatment groups at a two-sided significance level of 0.05. Assuming 15% loss to follow-up and 6% rate of potential suboptimal MRI quality, 212 participants were enrolled to maintain adequate power.

[0128] For study outcomes of LVEF, KCCQ-OSS, and 6MWD, treatment group differences were assessed using a mixed model for repeated measures (MM RM) with treatment group, time point, and treatment group*time interaction as fixed effects, and participant as a random effect with adjustment for age, sex, race / ethnicity, New York Heart Association functional class, HF etiology (ischemic vs non-ischemic), HF chronicity (acute vs chronic), estimated glomerular filtration rate, and baseline NT-proBNP. The primary outcome analysis for MRI-based EF included all participants with a depressed LVEF by MRI at baseline (LVEF <55%, N = 209). Participants with missing MRI data on follow-up were censored at the 6-month visit. Treatment effects are presented as least squares mean (LSM) differences with 95% confidence intervals. The composite outcome was analyzed using win-ratio methodology, with each participant in the polypill group compared with each participant in the enhanced usual care group in pairwise fashion according to the pre-specified hierarchy.

[0129] Clinical endpoints were analyzed using the Andersen-Gill model for recurrent events with robust variance estimation accounting for within-subject correlation. Both unadjusted and adjusted models were fitted, with adjustment for covariates similar to the primary outcome. Results were presented as hazard ratios with 95% confidence intervals. The rate of HF hospitalization or ED visit was also analyzed using Poisson regression models with persontime as an offset. Person-time was calculated from the randomization date to the final study visit for participants who completed the study, to the date of loss to follow-up (defined as the date they missed their scheduled follow-up visit), or to the date of death for those who died. Both unadjusted and adjusted models were fitted, with a similar adjustment as the primary outcome. Results were presented as rate ratios with 95% confidence intervals.

[0130] Among other outcomes, NT-proBNP was analyzed using an MMRM with the same adjustment strategy as for the primary outcome and presented as geometric means with 95% confidence intervals, and between-group comparisons were expressed as geometric mean ratios. Medication adherence by TDM was assessed as a binary outcome (adherent vs. non-301612543 - 41 -Atty. Docket No. UTSD.P4571WO / 1001378524adherent) using logistic regression. Results were presented as odds ratios with 95% confidence intervals.

[0131] Several sensitivity analyses were performed to assess the robustness of the study findings for the primary outcome. First, an analysis was performed that included the 3 participants with recovered LVEF (>55%) at the baseline MRI examination. Second, for participants with missing MRI-based EF on follow-up (N=25), sensitivity analyses were performed using the last observation carried forward approach to account for missing data. Third, an additional sensitivity analysis was performed, excluding participants without optimal-quality short-axis image MRI scans at baseline and follow-up (N=10). All analyses were conducted using R version 4.4.1 (R Foundation for Statistical Computing, Vienna, Austria). Statistical significance was defined as a two-sided p-value <0.05.301612543 - 42 -

Claims

Atty. Docket No. UTSD.P4571WO / 1001378524CLAIMSWhat is claimed is:

1. A medication dispensing system comprising:a pharmaceutical inventory system;a packaging inventory system;a medication packing system operable to:receive one or more empty capsules from the packaging inventory system,fill the one or more empty capsules with a quantified pharmaceutical received from the pharmaceutical inventory system, resulting in one or more filled capsules, andfill an empty container received from the packaging inventory system with the filled capsules, resulting in a filled container;a labelling system operable to provide a personalized label corresponding to the quantified pharmaceutical; anda user interface operable to receive a patient identifier from a user of the medication dispensing system, and the quantified pharmaceutical and the personalized label are based on the patient identifier received at the user interface.

2. The medication dispensing system of claim 1 ,wherein,the pharmaceutical inventory system, the packaging inventory system, the medication packaging system, and the labelling system are at least partly contained within a housing of the medication dispensing system.

3. The medication dispensing system of claim 2,wherein,the housing includes wheels providing mobility to the medication dispensing system.

4. The medication dispensing system of claim 1 ,wherein,the pharmaceutical inventory system stores a plurality of different medications, and301612543 - 43 -Atty. Docket No. UTSD.P4571WO / 1001378524the medication packing system is operable to fill an empty capsule with the plurality of different medications, based on a plurality of prescriptions associated with the patient identifier, such that the one or more filled capsules includes a polymedication pill corresponding to the plurality of prescriptions.

5. The medication dispensing system of claim 4,wherein,the user interface is operable to receive a plurality of different patient identifiers from a plurality of patients, andthe medication packing system is operable to fulfill a plurality of different prescriptions, using different quantified pharmaceuticals from the pharmaceutical inventory system, based on the plurality of different patient identifiers.

6. The medication dispensing system of claim 1 , further comprising:a plurality of cassettes of the pharmaceutical inventory system, a first individual cassette of the plurality of cassettes stores a first drug in bulk form, and a second individual cassette of the plurality of cassettes stores a second drug in bulk from, the second drug being a different drug than the first drug.

7. The medication dispensing system of claim 6,wherein,the pharmaceutical inventory system includes one or more sensors to detect a quantity of a stored drug in an individual cassette of the plurality of cassettes.

8. The medication dispensing system of claim 7, further comprising:an access door to the plurality of cassettes, operable responsive to a determination that the quantity of the stored drug in the individual cassette is below a predetermined threshold value.

9. The medication dispensing system of claim 1 ,wherein,the labelling system applies the personalized label to the filled container or the empty container.

10. The medication dispensing system of claim 1 ,wherein,301612543 - 44 -Atty. Docket No. UTSD.P4571WO / 1001378524the labelling system prints the personalized label and distributes, to the user, the personalized label separate from the filled container.

11. The medication dispensing system of claim 1 ,wherein,the packaging inventory system includes a first color-coded capsule corresponding to a first dosage time period and a second color-coded capsule corresponding to a second dosage time period.

12. A medication dispensing device comprising:a pharmaceutical inventory system;a packaging inventory system;a medication packing system operable to:receive one or more empty capsules from the packaging inventory system, fill the one or more empty capsules with a quantified pharmaceutical received from the pharmaceutical inventory system, resulting in one or more filled capsules, and fill an empty container received from the packaging inventory system with the filled capsules, resulting in a filled container;a labelling system operable to provide a personalized label corresponding to the quantified pharmaceutical;a housing at least partly enclosing the pharmaceutical inventory system, the packaging inventory system, the medication packing system, and the labelling system; anda user interface, coupled to the housing, operable to receive a patient identifier from a user of the medication dispensing system, and the quantified pharmaceutical and the personalized label are based on the patient identifier received at the user interface.

13. The medication dispensing device of claim 12, further comprising:a code scanner operable to detect the patient identifier.

14. The medication dispensing device of claim 12, further comprising:a refrigeration system operable to maintain a predefined temperature at the pharmaceutical inventory system.

15. The medication dispensing device of claim 14, further comprising:a battery power system operable to provide power to the refrigeration system.301612543 - 45 -Atty. Docket No. UTSD.P4571WO / 100137852416. The medication dispensing device of claim 13, further comprising:one or more cameras coupled to the housing and operable to generate video data of an exterior area proximate to the medication dispensing device.

17. The medication dispensing device of claim 16,wherein,the patient identifier is included in at least one of:a bar code;a QR code;a written or printed prescription on paper; ora prescription data transmission received at a communication system of the medication dispensing device.

18. A method of dispensing medication to a patient, the method comprising:storing medication at a pharmaceutical inventory system of a medication dispensing device;storing a plurality of empty capsules and a plurality of empty containers at a packaging inventory system of the medication dispensing device;receiving, at a user interface of the medication dispensing device, a patient identifier from a user of the medication dispensing system;filling, using a medication packing system of the medication dispensing device, one or more capsules of the plurality of empty capsules with a quantified pharmaceutical received from the pharmaceutical inventory system, resulting in one or more filled capsules, the quantified pharmaceutical being based on the patient identifier;filling, using the medication packing system, an empty container received from the packaging inventory system with the filled capsules, resulting in a filled container; andproviding, using a labelling system of the medication dispensing device, a personalized label corresponding to the quantified pharmaceutical.

19. The method of claim 18, further comprising:dispensing the filled container to the user via a dispensing outlet formed into a housing of the medication dispensing device.

20. The method of claim 18, further comprising:301612543 - 46 -Atty. Docket No. UTSD.P4571WO / 1001378524detecting, using one or more sensors, that an amount of a particular pharmaceutical stored at the pharmaceutical inventory system is below a predetermined threshold value, and generating a notification indicating that the amount of the particular pharmaceutical is below the predetermined threshold value.

21. A polypill formulation formed by medication dispensing system of claim 1.

22. The polypill formulation of claim 21, comprising a beta blocker, a renin-angiotensin-system (RAS) inhibitor, a sodium-glucose co-transporter 2 inhibitor (SGLT2i) and / or a mineralocorticoid receptor antagonist (MRA).

23. The polypill formulation of claim 22, wherein the beta blocker comprises metoprolol, optionally metoprolol succinate; the SGLT2i comprises empagliflozin; the MRA comprises spironolactone; or any combination thereof.

24. The polypill formulation of claim 23, comprising: (a) 10 mg of empagliflozin, (b) 12.5 mg of spironolactone, and (c) 25 mg, 50 mg, 100 mg, or 150 mg of metoprolol succinate.

25. A polypill formulation comprising:(a) a first pill comprising a beta blocker,(b) a second pill comprising a sodium-glucose co-transporter 2 inhibitor (SGLT2i), and (c) a third pill comprising a mineralocorticoid receptor antagonist (MRA), and(d) a gel capsule,wherein the gel capsule of (d) encapsulates the first, second, and third pills of (a), (b), and (c).

26. The polypill formulation of claim 25, comprising:(a) 25 mg, 50 mg, 100 mg, or 150 mg of metoprolol succinate(b) 10 mg of empagliflozin, and / or(c) 12.5 mg of spironolactone.

27. A method of treating a disease or condition in a subject, the method comprising administering a polypill formulation of any one of claims 21 to 26 to the subject.

28. The method of claim 27, wherein the disease or condition comprises heart failure, optionally wherein the disease or condition comprises heart failure with reduced ejection fraction (HFrEF).301612543 - 47 -

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