Implantable device for long-term delivery of drugs
Inventors
Martin, Francis J. • Kang, Ling-Ling
Assignees
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Publication Number
US-10391288-B2
Publication Date
2019-08-27
Expiration Date
Abstract
A device for sustained delivery of a poorly water soluble drug is described. A drug reservoir within the device, when in operation, contains an aqueous suspension of the drug mixed with a suspension of an excipient that, in one embodiment, generates acidic groups for a sustained period of time to maintain a desired pH in the aqueous suspension that in turn provides a constant concentration of a soluble form of the drug.
Core Innovation
The invention describes an implantable drug-delivery device and methods for delivering a therapeutic dose of a sparingly water soluble drug into an environment of use by using a device that includes a porous partition and an internal reservoir. The reservoir contains a formulation that, when hydrated, forms an aqueous suspension and includes a sparingly water soluble drug in both a soluble form and an insoluble form. The porous partition allows the soluble form of the drug to be released across the partition while retaining the insoluble form within the reservoir-side region.
The formulation further includes a solubility-modifying excipient that generates acidic groups for a period of between about 2-12 months. This acid generation maintains reservoir pH such that a concentration of drug in the soluble form is maintained, thereby supporting substantially constant-rate release. In the described approach, the delivery is dependent on pH of the drug formulation rather than on pore size and porosity-related effects of the porous partition.
The described system is configured so that delivery across the porous partition is driven by a maintained soluble drug concentration gradient, including diffusion across the porous partition, while insoluble material is retained. The partial content also states that delivery is independent of pore size of the porous partition with said porosity, using device geometry and partition configurations to support diffusion-based release and subcutaneous implantation.
Claims Coverage
The partial content includes two independent claims: one for delivering a sparingly water soluble drug into an environment of use, and one for treating a patient. Both center on pH-dependent delivery of a sparingly water soluble drug across a porous partition with delivery independent of pore size/porosity, enabled by a solubility-modifying excipient that generates acidic groups for 2-12 months and a reservoir formulation containing both soluble and insoluble drug forms.
Porous partition and reservoir formulation releasing soluble drug while retaining insoluble drug
A device comprising a porous partition with pores having a pore size and with a porosity, a reservoir and a formulation contained in the reservoir, wherein the formulation comprises a sparingly water soluble drug having a soluble form and an insoluble form and is configured so that, when the formulation is hydrated, a concentration of drug in the soluble form is released across the porous partition and a concentration of drug in the insoluble form is retained by the porous partition.
Solubility-modifying excipient generating acidic groups for 2-12 months
The formulation further comprises a solubility-modifying excipient that generates acidic groups for a period of between about 2-12 months to provide, when the formulation is hydrated, a concentration of drug in the soluble form for release across the porous partition while the insoluble-form drug concentration is retained by the porous partition.
Therapeutic dosing dependent on formulation pH and independent of porous partition pore size
Delivering a therapeutic dose of the drug for the period wherein delivering the therapeutic dose is dependent on pH of the drug formulation and independent of pore size of the porous partition with said porosity.
Implanting the device in a patient
A method for treating a patient wherein the device comprising the porous partition and reservoir formulation is implanted and delivering the therapeutic dose for the period is dependent on pH of the drug formulation and independent of pore size of the porous partition with said porosity.
Across the independent claims, the core claim coverage is the combination of a porous partition that releases the soluble-form fraction while retaining the insoluble-form fraction, a solubility-modifying excipient generating acidic groups for 2-12 months to maintain the soluble-form concentration, and therapeutic delivery that is dependent on formulation pH and independent of porous partition pore size/porosity.
Stated Advantages
Maintains an effectively constant soluble drug concentration for release across the porous partition over about 2-12 months.
Delivery is independent of pore size/porosity effects and is instead driven by maintained soluble concentration gradient; delivery depends on pH of the drug formulation.
Limited release without the solubility-modifying excipient versus improved near-zero-order release with formulations containing the solubility-modifying excipient.
Improved plasma levels in rats for at least one example drug.
Documented Applications
Delivering a sparingly water soluble drug into an environment of use using an implantable device that releases a therapeutic dose over about 2-12 months.
Treating a patient with a sparingly water soluble drug using an implanted device, including embodiments where implantation is subcutaneous.
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