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 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: 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 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: 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: 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 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: 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: Therapeutic agent delivery formulations for the sustained release of therapeutic agents from a Port Delivery System (PDS) implant is described in this application.

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 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 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: A therapeutic device to release a therapeutic agent comprises a porous structure coupled to a container comprising a reservoir. The reservoir comprises a volume sized to release therapeutic amounts of the therapeutic agent for an extended time when coupled to the porous structure and implanted in the 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: 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 (105) and therapeutic agent delivery formulations for the sustained release of therapeutic agents. In one aspect, described is a device to treat an ocular condition of an eye. The device has a proximal region. A tubular body (115) is coupled to the proximal region and has an outer diameter configured to be inserted at least in part into the eye. A reservoir (130) is in fluid communication with the tubular body and has a volume sized to receive an amount of a formulation of a therapeutic agent. One or more outlets (135) are in fluid communication with the reservoir and configured to release therapeutic amounts of the therapeutic agent into the eye for an extended time when the one or more outlets are positioned inside the eye.