Subcutaneous delivery of high concentration formulations
OwnerMariana DIMITROVA, Matthew J. HUDDLESTON +1inventors
InventorsMariana DIMITROVA, Matthew J. HUDDLESTON, Ql WANG
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Abstract
The present disclosure provides high concentration low viscosity defibrotide formulations administered via an automated injection device. The device is calibrated for optimum flow rate and administration of the high concentration low viscosity formulation.
Claims39
A method of preparing and/or administering a high concentration defibrotide formulation to a patient via an automated injection device,
- wherein the automated injection device includes
- a) a housing defining a central portion, wherein the housing has a circular profile and includes a spiral recess;
- b) a bladder positioned within the housing, the bladder including a first end, a second end, and a wall extending between the first end and the second end, the bladder being expandable, wherein the bladder wall includes an area of increased thickness along a side of the bladder wall, wherein the area of increased thickness deflects less than a remaining portion of the bladder wall during administration to affect the movement of the distal end of the bladder along an arcuate path;
- and
- c) a cannula disposed within the central portion of the housing and configured to be movable between multiple positions, including a pre-dispense position where the cannula is not in fluid communication with the bladder, and a dispense position where the cannula is in fluid flow communication with the bladder;
- wherein the high concentration defibrotide formulation comprises between 100 mg/mL to about 400 mg/mL of defibrotide, and a viscosity reducer at a concentration of between about 5 mM and about 100 mM, wherein the formulation has a viscosity between about 5 and about 70 cP when measured at a temperature of between 15° C. and 25° C., and an osmolality between about 240 mOsm/kg and about 1000 mOsm/kg, and is formulated for parenteral delivery to the patient;
- and wherein an inner diameter of the cannula ranges from about 0.08 mm to about 0.41 mm and further wherein the administering includes:
- disposing the cannula in the dispense position;
- introducing the high concentration defibrotide formulation under pressure to expand the bladder such that the second end of the bladder moves along an arcuate path around the central portion of the housing and an elastic force in the wall of the bladder expels the high concentration defibrotide formulation from the bladder and through the cannula at a flowrate between about 0.5 ml/hour to about 700 ml/hour.
The method of claim 24, wherein the high concentration defibrotide formulation is administered at a dosing regimen that provides improved patient quality of life by requiring a reduced administration volume and/or allowing less-frequent administration and/or a shorter duration of administration and/or convenience of administration on an outpatient basis.
An automated injection device for delivery of a high concentration defibrotide formulation, wherein the automated injection device includes
- a) a housing defining a central portion, wherein the housing has a circular profile and includes a spiral recess within which a second end of a bladder is positioned and moves along upon contraction and expansion;
- b) a bladder positioned within the housing, the bladder including a first end, a second end, and a wall extending between the first end and the second end, the bladder being expandable, wherein the bladder wall includes an area of increased thickness along a side of the bladder wall, where the area of increased thickness deflects less than a remaining portion of the bladder wall during administration to affect the movement of the distal end of the bladder along an arcuate path;
- c) a cannula disposed within the central portion of the housing and configured to be movable between multiple positions, including a pre-dispense position where the cannula is not in fluid communication with the bladder, and a dispense position where the cannula is in fluid flow communication with the bladder,
- wherein the bladder comprises a fluid formulation of a high concentration defibrotide formulation comprising between 100 mg/mL to about 400 mg/mL of defibrotide, and a viscosity reducer at a concentration of between about 5 mM and about 100 mM, wherein the formulation has a viscosity between about 5 and about 70 cP when measured at a temperature of between 15° C. and 25° C., and an osmolality between about 240 mOsm/kg and about 1000 mOsm/kg, and is formulated for parenteral delivery to the patient and wherein the inner diameter of the cannula ranges from about 0.08 mm to about 0.41 mm to result in a flowrate between about 0.5 ml/hour to about 700 ml/hour.
Dependencies are inferred from the claim text.