Controlled extended release of serotonin receptor anatagonist; alleviating sleep apnea; kits
Inventors
Rariy, Roman V. • Heffernan, Michael
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8512751-B2
Publication Date
2013-08-20
Expiration Date
Abstract
Pharmaceutical compositions are provided for the pharmacological treatment of breathing disorders and, more specifically, to compositions containing agents having serotonin receptor modulating activity for the alleviation of sleep apnea (central and obstructive) and other sleep-related breathing disorders wherein the active ingredients are released such as to extend effective blood plasma concentrations across the period of sleep.
Core Innovation
The invention provides a pharmaceutical composition for sleep-related breathing disorders using a serotonin receptor modulating agent, including an ondansetron composition. The treatment targets central sleep apnea and obstructive sleep apnea and provides dosing over a sleep period by using modified release dosing.
A core aspect is an ondansetron composition having an immediate release dose and a delayed release dose that results in a continuous period of therapeutically effective blood plasma ondansetron levels initiated by a first pulse shortly after administration and extended by a delayed second pulse. The described release timing creates a continuous period from about 6 to 14 hours from administration.
The disclosure further describes formulation strategies for the immediate and delayed ondansetron components, including delayed release and enteric/delayed coatings with polymers such as Eudragit L100, Eudragit S100, Eudragit L100-55, and Eudragit RL/RS, and dosage forms such as tablets, capsules, and layered constructions. The described examples include ondansetron-fluoxetine dosage forms with immediate/delayed/pulsatile/extended release concepts.
Claims Coverage
The document includes one independent claim covering a two-pulse immediate-then-delayed ondansetron dosing composition with defined plasma-level and exposure constraints, plus additional dependent claim refinements. The independent claim contains the central inventive features of the pulse-based modified release profile and the specified blood plasma concentration limits.
Two-pulse immediate and delayed release ondansetron with continuous therapeutic plasma exposure
A pharmaceutical composition comprising an immediate release dose of ondansetron and a delayed release dose of ondansetron, wherein release results in a therapeutically effective level of ondansetron in blood plasma for a continuous period initiated by a first pulse at from 0 to 2 hours from administration, followed by a delayed second pulse that extends the period to from 6 to 14 hours from administration.
Blood plasma ondansetron concentration limits for the modified release profile
The composition is defined such that ondansetron blood plasma levels have a Cmax below approximately 400 ng/mL, and the mean blood plasma concentration of ondansetron released from the composition is approximately 20 ng/mL at 14 hours from administration, approximately 10 ng/mL at 20 hours from administration, and approximately 8 ng/mL at 24 hours from administration.
Defined first and second pulse release timing windows
The release profile includes a first pulse released within 30 minutes after administration and a second pulse released between 1 and 4 hours after administration.
Continuous period duration constraint
The composition provides a continuous period after administration lasting for 7 to 12 hours.
SSRI selection for combined serotonin receptor modulation
The pharmaceutical composition further includes an SSRI selected from fluoxetine, paroxetine, milnacipran, sertraline, citalopram, escitalopram, or fluvoxamine.
Across the independent claim focus and dependent refinements, the inventive coverage centers on an immediate-release ondansetron dose followed by a delayed second pulse to sustain therapeutically effective blood plasma levels across a defined sleep-period window, while meeting specific pharmacokinetic concentration limits and optionally combining with selected SSRIs.
Stated Advantages
Sustains therapeutically effective ondansetron blood plasma levels for a continuous period initiated by a first pulse and extended by a delayed second pulse from 6 to 14 hours from administration.
Maintains ondansetron blood plasma exposure while limiting Cmax to below approximately 400 ng/mL and achieving specified mean plasma concentrations at later time points (14, 20, and 24 hours).
Enables combined serotonin receptor modulation via an SSRI selected from named agents.
Documented Applications
Pharmaceutical treatment of sleep-related breathing disorders, including central sleep apnea and obstructive sleep apnea, using serotonin receptor modulating agents and ondansetron dosing profiles over the sleep period.
Use of ondansetron in combination with SSRIs such as fluoxetine in treatment contexts involving sleep-related breathing disorders.
Interested in licensing this patent?