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.

A droplet generating method includes the steps of providing a micro-pipe having an outlet end; providing a liquid driving device to generate a flow of a first liquid; locating and positioning the micro-pipe which extends along a vertical longitudinal axis; connecting the liquid driving device with the micro-pipe so that the first liquid flows and is emitted out from the outlet end; providing a container, which is positioned at least in-part below the micro-pipe and adapted to contain a second liquid including a liquid surface disposed at a position located between a highest and a lowest positions; and either vertically or horizontally vibrating the micro-pipe, and thereby forming a plurality of droplets of the first liquid emitted from the outlet end at a position below the liquid surface of the second liquid.

A droplet generating method includes the steps of providing a micro-pipe having an outlet end; providing a liquid driving device to generate a flow of a first liquid; locating and positioning the micro-pipe which extends along a vertical longitudinal axis; connecting the liquid driving device with the micro-pipe so that the first liquid flows and is emitted out from the outlet end; providing a container, which is positioned at least in-part below the micro-pipe and adapted to contain a second liquid including a liquid surface disposed at a position located between a highest and a lowest positions; and either vertically or horizontally vibrating the micro-pipe, and thereby forming a plurality of droplets of the first liquid emitted from the outlet end at a position below the liquid surface of the second liquid.

A droplet generating method includes: providing a micro-pipe for dispensing a first liquid and a container containing a second liquid; providing a moving and locating device for positioning the micro-pipe over the container; providing a liquid driving device connecting to the micro-pipe through a connecting tube; providing a vibrating equipment connected to the micro-pipe for vibrating the micro-pipe; forming a relative periodic vibration between the micro-pipe and the container so that the outlet end of the micro-pipe is displaced to touch the second liquid in the container during a relative periodic vibration; and dispensing the first liquid in the micro-pipe out from the outlet end of the micro-pipe during the relative periodic vibration to generate a plurality of droplets of the first liquid in the second liquid which is induced by a force of the second liquid imposed on the first liquid at the outlet end.

A droplet generating method includes: providing a micro-pipe for dispensing a first liquid and a container containing a second liquid; providing a moving and locating device for positioning the micro-pipe over the container; providing a liquid driving device connecting to the micro-pipe through a connecting tube; providing a vibrating equipment connected to the micro-pipe for vibrating the micro-pipe; forming a relative periodic vibration between the micro-pipe and the container so that the outlet end of the micro-pipe is displaced to touch the second liquid in the container during a relative periodic vibration; and dispensing the first liquid in the micro-pipe out from the outlet end of the micro-pipe during the relative periodic vibration to generate a plurality of droplets of the first liquid in the second liquid which is induced by a force of the second liquid imposed on the first liquid at the outlet end.

The invention provides methods for the preparation of particles including one or more agents, e.g., therapeutic or diagnostic agents. The particles can be formed by creating droplets of a first liquid, e.g., including an agent, and removing the first liquid, e.g., through its dispersal in a second liquid and/or evaporation, to solidify the droplets. Advantageously, the process of forming the particles does not significantly alter the structure or activity of the agents and may enhance the stability of the agents. For example, the particles may be stored for long periods of time without significant loss of activity, and in some embodiments, without the need for refrigeration. These particles may be used to generate stabilized pharmaceutical compositions for storage or other logistical purposes, pharmaceutical suspensions, pharmaceutical powder formulations (e.g., inhalable powders, injectable powders), creams or other topical pastes, nutraceuticals, or cosmetics.

The invention provides methods for the preparation of particles including one or more agents, e.g., therapeutic or diagnostic agents. The particles can be formed by creating droplets of a first liquid, e.g., including an agent, and removing the first liquid, e.g., through its dispersal in a second liquid and/or evaporation, to solidify the droplets. Advantageously, the process of forming the particles does not significantly alter the structure or activity of the agents and may enhance the stability of the agents. For example, the particles may be stored for long periods of time without significant loss of activity, and in some embodiments, without the need for refrigeration. These particles may be used to generate stabilized pharmaceutical compositions for storage or other logistical purposes, pharmaceutical suspensions, pharmaceutical powder formulations (e.g., inhalable powders, injectable powders), creams or other topical pastes, nutraceuticals, or cosmetics.

A spray drying process and apparatus for drying a spray dryable liquid composition to a spray dried powder is described, in which the spray dryable liquid composition contains no carrier. The spray dryable liquid composition is processed at a solids concentration not exceeding 80% by weight, based on total weight of the spray dryable liquid composition, being atomized to generate an atomized spray of liquid particles of the spray dryable liquid composition into a spray drying chamber, in which the atomized spray is contacted with a stream of drying fluid flowed at temperature not exceeding 100° C. into the spray drying chamber, to form the spray dried powder.

A spray drying process and apparatus for drying a spray dryable liquid composition to a spray dried powder is described, in which the spray dryable liquid composition contains no carrier. The spray dryable liquid composition is processed at a solids concentration not exceeding 80% by weight, based on total weight of the spray dryable liquid composition, being atomized to generate an atomized spray of liquid particles of the spray dryable liquid composition into a spray drying chamber, in which the atomized spray is contacted with a stream of drying fluid flowed at temperature not exceeding 100° C. into the spray drying chamber, to form the spray dried powder.

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.