Diketopiperazine microparticles with defined specific surface areas
Inventors
Grant, Marshall L. • Stowell, Grayson W. • Menkin, Paul • Freeman, Jr., John J.
Assignees
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Publication Number
US-12383552-B2
Publication Date
2025-08-12
Expiration Date
Abstract
Disclosed herein are diketopiperazine microparticles having a specific surface area of less than about 67 m2/g. The diketopiperazine microparticle can be fumaryl diketopiperazine and can comprise a drug such as insulin.
Core Innovation
The described invention relates to an inhalation system using a dry powder inhaler and a dry powder formulation comprising crystalline microparticles of fumaryl diketopiperazine having a specific surface area of between about 35 m2/g and about 67 m2/g. The formulation further comprises a prostaglandin adsorbed to the microparticles. The inhaler includes a flow path passing through an area of powder containment and a flow path bypassing the area of powder containment, with defined proportions of total flow through and bypassing the powder containment area in use.
The core concept is that controlling the specific surface area (SSA) of fumaryl diketopiperazine microparticles changes aerodynamic performance, including respirable fraction on fill (RF/fill), and also affects drug adsorption onto the microparticle surfaces. The disclosed discussion links SSA to how crystal size and nucleation-growth develop during pH-induced crystallization and during freeze-drying or lyophilization, and describes how SSA relates to RF/fill and to temperature.
The invention also addresses adsorption behavior for active agents such as peptides and hormones, including insulin and other listed active agents, by adsorption onto microparticle surfaces, with attention to how SSA supports adsorption while avoiding adverse adsorption-related effects described for insulin. Example studies described include measurement of SSA and measurement of aerodynamic performance using impactor approaches, alongside comparisons across unloaded versus active-agent-loaded formulations and across different dry powder inhaler delivery systems.
Claims Coverage
The document provides two independent claims. Each independent claim centers on an inhalation system that combines crystalline fumaryl diketopiperazine microparticles with a specified SSA range and a prostaglandin adsorbed to the microparticles, together with a dry powder inhaler flow-path arrangement involving powder containment and bypass flow.
Specific surface area FDKP microparticles with prostaglandin adsorbed and containment/bypass flow split
An inhalation system comprising a dry powder inhaler and dry powder formulation comprising crystalline microparticles of fumaryl diketopiperazine having a specific surface area of between about 35 m2/g and about 67 m2/g, and a prostaglandin adsorbed to the microparticles, wherein the inhaler has a flow path passing through an area of powder containment and a flow path bypassing the area of powder containment, wherein in use 10-70% of the total flow exiting the inhaler passes through the area of powder containment and 90-30% of the total flow exiting the inhaler bypasses the area of powder containment.
Combining containment and bypass flow prior to exiting the mouthpiece for FDKP prostaglandin formulation
An inhalation system comprising a dry powder formulation comprising crystalline microparticles of fumaryl diketopiperazine, having a specific surface area of between about 35 m2/g and about 67 m2/g, and a prostaglandin adsorbed to the microparticles, and a dry powder inhaler comprising a mouthpiece and a powder containment area wherein the inhaler has a flow path passing through the powder containment area and a flow path bypassing the powder containment area wherein the flow through the powder containment area and the flow bypassing the powder containment area combine prior to exiting the mouthpiece.
Across the independent claims, the inventive coverage is directed to crystalline fumaryl diketopiperazine microparticles with a specified SSA range, a prostaglandin adsorbed to the microparticles, and a dry powder inhaler flow-path configuration involving powder containment and bypass flow.
Stated Advantages
Improves aerodynamic performance, including higher respirable fraction on fill (RF/fill), by controlling the specific surface area (SSA) of the fumaryl diketopiperazine microparticles.
Supports drug adsorption onto the microparticle surfaces through SSA-dependent behavior of the crystalline microparticles.
Documented Applications
Pulmonary drug delivery using an inhalation system with a dry powder inhaler and dry powder formulation comprising crystalline fumaryl diketopiperazine microparticles.
Dry powder inhaler testing and aerodynamic performance evaluation using SSA measurements and impactor-based respirable fraction on fill measurements.
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