Abstract: An injectable formulation of therapeutic agent may comprise the therapeutic agent and a stabilizer such that a substantial portion of the stabilizer remains in the therapeutic device to stabilize the therapeutic agent when the therapeutic agent is released from the therapeutic device. The injectable formulation may comprise one or more of binding agent particles or erodible material particles, such that the formulation can be injected into the therapeutic device. The binding agent particles can bind reversibly to the therapeutic agent so as to modulate release of the therapeutic agent, and the erodible material particles can generate protons of an acid so as to increase stability of the therapeutic agent and may modulate release of the therapeutic agent. The therapeutic agent can be combined with one or more of the stabilizer, the binding agent particles or the erodible particles to increase stability of the therapeutic agent and may modulate release.

Abstract: Methods and apparatus provide treatment with a first therapeutic agent and a second therapeutic agent for an extended time. The first therapeutic agent may comprise a VEGF inhibitor and the second therapeutic agent may comprise an antiinflammatory, such as a non-steroidal anti-inflammatory, for example a cyclooxygenase inhibitor. One or more of the first therapeutic agent or the second therapeutic agent can be injected into the eye, for example injected into a therapeutic device implanted into the eye to release the injected therapeutic agent for an extended time.

Abstract: An injectable formulation of therapeutic agent may comprise the therapeutic agent and a stabilizer such that a substantial portion of the stabilizer remains in the therapeutic device to stabilize the therapeutic agent when the therapeutic agent is released from the therapeutic device. The injectable formulation may comprise one or more of binding agent particles or erodible material particles, such that the formulation can be injected into the therapeutic device. The binding agent particles can bind reversibly to the therapeutic agent so as to modulate release of the therapeutic agent, and the erodible material particles can generate protons of an acid so as to increase stability of the therapeutic agent and may modulate release of the therapeutic agent. The therapeutic agent can be combined with one or more of the stabilizer, the binding agent particles or the erodible particles to increase stability of the therapeutic agent and may modulate release.

Abstract: The present disclosure relates to stable formulations of receptor tyrosine kinase inhibitors (TKI), e.g., pazopanib; methods of preparation thereof; and use of the disclosed formulations in sustained delivery of the active agent to a target site. The disclosure further relates to methods of converting one polymorphic Form of a TKI to another polymorphic Form and/or an amorphous form.

Abstract: An injector apparatus comprises an elongate structure having one or more openings positionable near a penetrable barrier of an implantable device so as to receive fluid of the implantable device. The apparatus comprises a needle and a sheath extending over at least a portion of the needle. The elongate structure may comprise a distal tip to penetrate tissue and the penetrable barrier, and a distal opening near the tip to release therapeutic fluid into the implantable chamber. In many embodiments the distal tip, the distal opening, and the plurality of openings are separated from a stop that engages a tissue of the patient and limit penetration depth such that the distal opening and the plurality of openings are located along an axis of the implantable device to increase an efficiency of the exchange.

Abstract: Methods and apparatus provide treatment with a first therapeutic agent and a second therapeutic agent for an extended time. The first therapeutic agent may comprise a VEGF inhibitor and the second therapeutic agent may comprise an antiinflammatory, such as a non-steroidal anti-inflammatory, for example a cyclooxygenase inhibitor. One or more of the first therapeutic agent or the second therapeutic agent can be injected into the eye, for example injected into a therapeutic device implanted into the eye to release the injected therapeutic agent for an extended time.

Abstract: Described are implantable therapeutic devices, systems and methods to treat a patient. The device includes a hollow refillable housing for implantation within the posterior segment of an eye through a penetration in the sclera including a proximal retention structure protruding outward from a proximal end region of the housing, an access portion opening, and a penetrable barrier positioned at least in part within the access portion opening, the penetrable barrier configured to be repeatedly penetrated. A rigid porous structure is positioned within a region of the housing away from the access portion opening into a reservoir chamber extends along an axis between the penetrable barrier and the porous structure includes a volume sized to deliver therapeutic amounts of a therapeutic agent to the eye for an extended period of time. A cover is coupled to at least an upper surface of the proximal retention structure.

Abstract: Described herein is an apparatus to insert an implantable therapeutic device into a patient. The apparatus includes a proximal handle and a distal placement portion coupled to the proximal handle and configured to hold the implantable therapeutic device. The distal placement portion includes a first side having a first engagement structure at a distal end of the first side, the first engagement structure configured to surround at least a first portion of a proximal end region of the implantable therapeutic device. The distal placement portion includes a second, opposite side having a second engagement structure at a distal end of the second side, the second engagement structure configured to surround at least a second, opposite portion of the proximal end region of the implantable therapeutic device.

Abstract: An apparatus to treat a patient comprises a container to receive fluid of a device implanted in the eye. The fluid of the device can be analyzed to determine a component of the vitreous humor of the eye.

Abstract: The present disclosure relates to stable formulations of receptor tyrosine kinase inhibitors (TKI), e.g., pazopanib; methods of preparation thereof; and use of the disclosed formulations in sustained delivery of the active agent to a target site. The disclosure further relates to methods of converting one polymorphic Form of a TKI to another polymorphic Form and/or an amorphous form.

Abstract: A delivery device that allows for the sustained release of an agent, particularly useful for the sustained release of a therapeutic agent to limited access regions, such as the posterior chamber of the eye and inner ear. The delivery device is minimally invasive, refillable and may be easily fixed to the treatment area. The delivery device includes a hollow body with an inlet port at its proximal end for insertion of the agent, a reservoir for holding the agent and a delivery mechanism for the sustained delivery of the agent from the reservoir to the patient.

Abstract: Methods and apparatus provide a therapeutic fluid to devices implanted in the body, for example to containers of devices implanted in the eye of a patient. The methods and apparatus may comprise an injector to increase an amount of therapeutic agent injected into the device implanted in the eye, or a structure to receive the therapeutic fluid within the device implanted in the eye, or combinations thereof. The device implanted in the eye may comprise a reservoir chamber having a fluid with a density different than the therapeutic fluid, and the apparatus can be adapted to at least partially separate the implanted device fluid from therapeutic fluid within the reservoir chamber to increase and amount of therapeutic fluid placed in the reservoir chamber.

Abstract: An implantable device for delivering a therapeutic agent to treat an ear of a patient includes a body having a distal end region and a proximal end region. The body defines, at least in part, a reservoir configured to contain the therapeutic agent. The device includes a shaft attached to the distal end region of the body and a lumen extending through the shaft having at least one inlet at a proximal end region in fluid communication with the reservoir and at least one outlet at a distal end region. Upon implantation of the body in a region of the ear, a length of the shaft is sufficient to extend from the body to at least the round window membrane of the ear. The device is configured to deliver the therapeutic agent to the ear from the reservoir via passive diffusion. Related devices and methods are described.

Abstract: An apparatus to treat a patient comprises a container to receive fluid of a device implanted in the eye. The fluid of the device can be analyzed to determine a component of the vitreous humor of the eye.

Abstract: Described are implantable therapeutic devices, systems and methods to treat a patient. The device includes a hollow refillable housing for implantation within the posterior segment of an eye through a penetration in the sclera including a proximal retention structure protruding outward from a proximal end region of the housing, an access portion opening, and a penetrable barrier positioned at least in part within the access portion opening, the penetrable barrier configured to be repeatedly penetrated. A rigid porous structure is positioned within a region of the housing away from the access portion opening into a reservoir chamber extends along an axis between the penetrable barrier and the porous structure includes a volume sized to deliver therapeutic amounts of a therapeutic agent to the eye for an extended period of time. A cover is coupled to at least an upper surface of the proximal retention structure.

Abstract: The present disclosure relates to stable formulations of receptor tyrosine kinase inhibitors (TKI), e.g., pazopanib; methods of preparation thereof; and use of the disclosed formulations in sustained delivery of the active agent to a target site. The disclosure further relates to methods of converting one polymorphic Form of a TKI to another polymorphic Form and/or an amorphous form.

Abstract: Described are implantable devices having reservoirs for the sustained release of therapeutic agents. The devices are configured to be at least partially implanted in an eye and include a retention structure and a penetrable element coupled to and extending within at least a portion of the proximal end region of the device. The device includes a porous drug release element is positioned in fluid communication with an outlet of the device and a reservoir having a volume configured to contain one or more therapeutic agents in fluid communication with the outlet through the porous drug release element. The device is at least partially inserted along an axis of insertion.

Abstract: Methods and apparatus provide a therapeutic fluid to devices implanted in the body, for example to containers of devices implanted in the eye of a patient. The methods and apparatus may comprise an injector to increase an amount of therapeutic agent injected into the device implanted in the eye, or a structure to receive the therapeutic fluid within the device implanted in the eye, or combinations thereof. The device implanted in the eye may comprise a reservoir chamber having a fluid with a density different than the therapeutic fluid, and the apparatus can be adapted to at least partially separate the implanted device fluid from therapeutic fluid within the reservoir chamber to increase and amount of therapeutic fluid placed in the reservoir chamber.

Abstract: A therapeutic device that can release a therapeutic agent comprising a porous structure coupled to a container comprising a reservoir. The reservoir can comprise a volume sized to release therapeutic amounts of the therapeutic agent for an extended time when coupled to the porous structure and implanted in a patient. The porous structure may comprise a first side coupled to the reservoir and a second side to couple to the patient to release the therapeutic agent. The length of the channels extending from the first side to the second side may comprise an effective length greater than a distance across the porous structure from the first side to the second side. The therapeutic device may comprise a penetrable barrier to inject therapeutic agent into the device when implanted in the patient.

Abstract: Described herein is an apparatus to insert an implantable therapeutic device into a patient. The apparatus includes a proximal handle and a distal placement portion coupled to the proximal handle and configured to hold the implantable therapeutic device. The distal placement portion includes a first side having a first engagement structure at a distal end of the first side, the first engagement structure configured to surround at least a first portion of a proximal end region of the implantable therapeutic device. The distal placement portion includes a second, opposite side having a second engagement structure at a distal end of the second side, the second engagement structure configured to surround at least a second, opposite portion of the proximal end region of the implantable therapeutic device.