Implantable medical devices for extended release of therapeutic agents
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Publication Number
US-10688056-B2
Publication Date
2020-06-23
Expiration Date
Abstract
The invention pertains to implantable medical devices for controlled delivery of therapeutic agents. Some devices according to the invention have a titanium reservoir, and a porous titanium oxide based membrane to control the rate of release of the therapeutic agent. The reservoir contains a formulation of the active agent, including a stabilizer for the active agent, wherein the stabilizer is provided in an extended release configuration.
Core Innovation
An implantable drug delivery system is described that uses a metal capsule suitable for implantation, with a reservoir encapsulated by the metal capsule. The reservoir contains a pharmaceutical composition including a water soluble therapeutic agent with an equilibrium solubility at room temperature of more than 1.0×10^-3 M and a stability enhancing agent. The system further includes at least one nanoporous membrane in fluid contact with the reservoir, where the stability enhancing agent is a low solubility acid with a maximum solubility no greater than 5% w/v.
The disclosure addresses stability of a water soluble therapeutic agent by providing the stability enhancing agent as a low solubility acid in an implantable extended-release configuration. The stability enhancing agent is formulated to maintain a stabilizing microenvironment that reduces premature depletion during release of the therapeutic agent. In particular, the extended-release configuration is described as providing slower release of the therapeutic agent than release of the stabilizer, thereby supporting retention of the therapeutic agent’s stability attributes over time.
The document describes compositions and components including nanoporous membrane structures such as titania nanotube membranes and nanochannels, and a capsule/reservoir arrangement in which the therapeutic agent and stability enhancing agent are co-formulated. Examples include peptides and proteins, including exenatide as a GLP-1 receptor agonist, and stability enhancing agents such as biodegradable polymer stabilizer configurations and low solubility acids/antioxidants within extended-release configurations. A forced-degradation study is described showing improved retention of exenatide purity with co-formulated material compared to exenatide alone under conditions including air/oxygen, with analysis by HPLC.
Claims Coverage
The document includes two independent claims. Collectively, the claim set covers an implantable drug delivery system and a method of treating a disease by administering the system, each centered on a water soluble therapeutic agent with an equilibrium solubility at room temperature above 1.0×10^-3 M together with a low solubility acid stabilizing agent having a maximum solubility no greater than 5% w/v provided in connection with at least one nanoporous membrane and, for treatment, an extended release configuration.
Metal capsule reservoir with water soluble therapeutic agent and low solubility acid stabilizer
An implantable drug delivery system including a metal capsule suitable for implantation, a reservoir encapsulated by the metal capsule with a pharmaceutical composition containing a water soluble therapeutic agent with an equilibrium solubility at room temperature of more than 1.0×10^-3 M and a stability enhancing agent, where the stability enhancing agent is a low solubility acid with a maximum solubility no greater than 5% w/v.
Nanoporous membrane in fluid contact with reservoir and extended release stabilizer configuration
At least one nanoporous membrane in fluid contact with the reservoir, wherein the stability enhancing agent is provided in an extended release configuration.
Across the independent claims, the inventive coverage requires an implantable metal capsule with an encapsulated reservoir holding a water soluble therapeutic agent (equilibrium solubility at room temperature >1.0×10^-3 M) and a stability enhancing low solubility acid (maximum solubility ≤5% w/v). The system further requires at least one nanoporous membrane in fluid contact with the reservoir, and the treatment method claim specifies that the stability enhancing agent is provided in an extended release configuration.
Stated Advantages
Supports retention of therapeutic agent stability by providing a stabilizing microenvironment and reducing premature depletion.
Improves exenatide purity retention over time in a forced-degradation study with co-formulated material compared to exenatide alone.
Documented Applications
Treating a disease in a subject in need thereof by administering a therapeutically effective amount of a water soluble therapeutic agent contained within the implantable drug delivery system.
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