# US 11,077,063 B2 · Apparatus and method for cryogranulating a pharmaceutical composition > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,077,063 B2 - Document ID: US11077063B2 - Status: Granted - Kind: B2 - Application number: 16/675,471 - Filed: 2019-11-06 - Published: 2020-03-05 - Granted: 2021-08-03 - Earliest claimed: 2009-11-02 - Assignees: MannKind Corporation - Applicants: MannKind Corporation - Inventors: Edwin Amoro; Karel Vanackere; Michael A. White - Web page: https://patentgrep.com/patent/US11077063B2 ## CPC - A61K 9/1682: {Processes} - A61J 3/00: Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms - A61K 9/16: Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)} - A61K 9/1617: {Organic compounds, e.g. phospholipids, fats} - A61K 38/28: Insulins - B01J 2/06: in a liquid medium - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE - B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS ## Abstract Cryogranulation systems with improved dispenser assemblies are provided for use in manufacturing frozen pellets of pharmaceutical substances in a fluid medium. Methods of cryogranulating the pharmaceutical substance in the fluid medium are also provided. In particular embodiments, the dispenser assembly is used with suspensions or slurries of pharmaceutical compositions including biodegradable substances, such as proteins, peptides, and nucleic acids. In certain embodiments, the pharmaceutical substance can be adsorbed to any pharmaceutically acceptable carrier particles suitable for making pharmaceutical powders. In one embodiment, the pharmaceutical carrier can be, for example, diketopiperazine-based microparticles. The dispenser assembly improves the physical characteristics of the cryopellets formed and minimizes product loss during processing. ## Claims ### Claim 1 A cryogranulation system, comprising: at least one tray configured to carry a flow of a cooling agent; a mechanism configured to deliver the cooling agent to the at least one tray; a dispenser assembly configured to supply a pharmaceutical composition including diketopiperazine-based microparticles in a fluid medium into the flow of the cooling agent in the tray to produce, after interaction of the pharmaceutical composition with the cooling agent, pellets of the pharmaceutical composition, wherein the dispenser assembly includes first and second rows of dispenser ports, the rows of dispenser ports being disposed perpendicularly with respect to the flow of the cooling agent, wherein the dispenser ports of the first and second rows are angled with respect to vertical and wherein the dispenser ports of the first row are disposed at opposite angles with respect to the dispenser ports of the second row; and a transport assembly configured to separate the pellets from the cooling agent and to transport the pellets to a pellet receptacle. ### Claim 2 (depends on 1) A cryogranulation system as defined in claim 1, wherein the diketopiperazine-based microparticles comprise fumaryl diketopiperazine microparticles. ### Claim 3 (depends on 1) A cryogranulation system as defined in claim 1, wherein the diketopiperazine-based microparticles comprise fumaryl diketopiperazine microparticles loaded with a pharmaceutically active agent. ### Claim 4 (depends on 1) A cryogranulation system as defined in claim 1, wherein the dispenser ports of the dispenser assembly each include an upper conduit of a first inner diameter and a lower conduit of a second inner diameter. ### Claim 5 (depends on 1) A cryogranulation system as defined in claim 1, wherein the dispenser assembly includes a heater configured to prevent the pharmaceutical composition from freezing during dispensing. ### Claim 6 A cryogranulation system comprising: a dispenser assembly, a reservoir for holding a source of a cooling agent, a pump assembly for delivering a pharmaceutical suspension; a pump system for delivering the cooling agent, a transport system for transporting formed pellets to a receptacle and an exhaust system; wherein the dispenser assembly comprises a housing and a dispenser subassembly which comprises a first element having one or more inlet ports, a second element having a plurality of dispenser ports; and a securing mechanism for holding the first and second elements together; said dispenser subassembly adaptable to said housing and having an internal volume for receiving and dispensing the pharmaceutical suspension to be pelletized, wherein the dispenser ports of the dispenser subassembly each include an upper conduit of a first inner diameter and a lower conduit of a second inner diameter, wherein the dispenser ports of the dispenser subassembly include first and second rows of dispenser ports, the rows being disposed perpendicularly with respect to the flow of cooling agent, wherein the first and second rows of dispenser ports are angled with respect to vertical, wherein the dispenser ports of the first row are disposed at opposite angles with respect to the dispenser ports of the second row, and wherein the dispenser assembly includes a heater configured to prevent the pharmaceutical suspension from freezing during dispensing.