Bioerodible implant for long-term drug delivery and associated methods of manufacture and use
Inventors
BAILLIE, John H. • BAILLIE, Ruth • Blouin, George • Farahani, Newsha • MARX, Christopher
Assignees
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Publication Number
US-10188602-B2
Publication Date
2019-01-29
Expiration Date
Abstract
A drug delivery system is provided in the form of a controlled release, bioerodible pellet for subdermal implantation. The pellet is bioerodible, and provides for the sustained release of a pharmacologically active agent over an extended time period. As such, the drug delivery system finds significant utility in chronic drug administration. Bioerosion products are water soluble, bioresorbed, or both, obviating the need for surgical removal of the implant. Methods for manufacturing and using the drug delivery system are also provided.
Core Innovation
The document describes a bioerodible controlled-release pellet system for chronic drug delivery that is subdermally implantable. It addresses delivery performance by reducing a release tail and maintaining an effective vs sub-effective drug delivery period, while avoiding surgical removal and achieving pharmacologically active agent release over an extended period.
The core-and-shell architecture tunes controlled release by placing a pharmacologically active agent in a shell composition and/or a core composition, with the shell and core formed as concentric regions around an elongated segment. The document further characterizes composition behavior, including lipophilic pellet components and hydrophilic components, and discusses limits relating to aqueous solubility and bioerosion products being water soluble/bioresorbable.
The document also provides a method of making a core-and-shell type pellet using a pin/tube/funnel assembly, where a shell composition is cooled and hardened around an upper segment, and then a molten core composition is drawn into the hardened shell. It further describes manufacturing assemblies for monolithic pellets and core-and-shell pellets and includes reported dissolution and in vivo plasma relationships correlating released drug exposure with pellet geometry and excipient selection.
Claims Coverage
The partial content identifies one independent claim that covers a method for making a core-and-shell type pellet for controlled release using a specific pin/tube/funnel arrangement. Additional dependent claims refine active-agent placement, quantitative distribution thresholds, active-agent solubility limits, and enumerated therapeutic agent categories.
Pin/tube/funnel shell formation by drawing a molten shell into a concentric space
Providing an elongated pin with axially aligned cylindrical adjacent segments of different diameters, providing a pelleting tube sized to provide a sealing fit between the inner surface and the lower segment, and providing a funnel; inserting the pin tip into the lower tube opening and moving the pin toward the funnel until the lower segment is within the tube and the upper segment protrudes; placing a molten shell composition in the funnel; gradually withdrawing the lower segment to lower the upper segment into the tube while simultaneously drawing the shell composition into a concentric space between the upper segment and the inner surface; and allowing the shell composition to cool and harden into a shell formed around the upper segment within the concentric space.
Core formation by drawing molten core composition into the hardened shell
Placing a molten core composition into the funnel and gradually lowering the upper segment within the tube to draw the core composition into the shell to form a core, wherein the shell composition and/or core composition contain a pharmacologically active agent.
Active-agent localization in the core with a quantitative threshold
The method such that at least about 80 wt.% of the pharmacologically active agent in the pellet is in the core.
Active-agent localization in the shell with a quantitative threshold
The method such that at least about 80 wt.% of the pharmacologically active agent in the pellet is in the shell.
Core and shell each containing at least a quantitative amount of the active agent
The method directed to a pellet whose core and shell each contain at least about 20 wt.% of a pharmacologically active agent.
Pharmacologically active agent aqueous solubility limitation
The method including using a pharmacologically active agent with aqueous solubility of less than about 50 mg/mL.
Enumerated anticancer agent categories
The method further specifying that the anticancer agent is selected from an anti-metabolite, an anti-microtubule agent, a cytotoxic antibiotic, a topoisomerase inhibitor, an aromatase inhibitor, a GnRH analogue, a hormone receptor antagonist, a hormonal agent, an anti-angiogenic agent, an anti-metastatic agent, and a combination thereof.
Overall, the claim coverage emphasizes making a core-and-shell controlled-release pellet by forming a cooled hardened shell around an upper segment and then drawing a molten core composition into that shell, with additional refinements specifying where the pharmacologically active agent resides using quantitative wt.% thresholds, applying an aqueous solubility limit, and narrowing anticancer agents to a specified list.
Stated Advantages
Avoids surgical removal and reduces a release tail while supporting an effective vs sub-effective drug delivery period.
Documented Applications
Chronic drug delivery using subdermal implantation for pharmacologically active agents.
Antipsychotics.
Antivirals/HIV.
Anti-inflammatories.
Anticonvulsants.
Anticancer.
Hormones/contraception.
Vitamins.
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