PDE5 inhibitor powder formulations and methods relating thereto
Inventors
Xu, Zhen • SMYTH, HUGH • Gibbons, Aileen • Shreeniwas, Revati • Soni, Pravin • Deaton, Dan • Hannon, James • Lermer, Stephen • Curtis, Robert • Donovan, Martin J.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11911390-B2
Publication Date
2024-02-27
Expiration Date
Abstract
Novel dry powder compositions comprising and methods relating thereto are provided. The dry powder compositions comprise PDE5 inhibitors, such as vardenafil, or pharmaceutically acceptable salts or esters thereof. The dry powder compositions may optionally include an carrier/excipient. The concentration of active agent may be at least about 2% by weight. Methods of aerosolizing the dry powder compositions and using them to treat various diseases are also disclosed.
Core Innovation
The invention relates to a powder pharmaceutical composition comprising vardenafil hydrochloride as a PDE5 inhibitor, together with lactose particles arranged in two fractions. A first fraction consists of fine lactose particles, and a second fraction consists of lactose particles having an average diameter of about 5 μm to about 90 μm, with specified upper limits on the amount of vardenafil hydrochloride and the fine lactose particles.
The claimed composition defines quantitative particle-size and content relationships between the PDE5 inhibitor and the lactose fractions. Fine lactose particle sizing is characterized by an average diameter limitation, and the PDE5 inhibitor content is limited to up to about 20% by weight relative to the total weight of the overall pharmaceutical composition, while the first fine lactose fraction is present at up to about 10% by weight relative to the lactose in the composition.
The disclosed powder composition is framed as a pulmonary delivery formulation for aerosolization using an inhaler and dispersion chamber with an oscillating actuator. The document also supports the use of lactose and particle engineering concepts for aerosol performance, including metrics such as ED%, RF%, FPF(ED), and MMAD, tied to solid form characterization and stability considerations for vardenafil.
Claims Coverage
The independent claim covers a powder pharmaceutical composition with two lactose particle fractions and defined weight limits for vardenafil hydrochloride and the fine lactose fraction, anchored to a PDE5 inhibitor content constraint and lactose particle size fractioning. Dependent claims refine the composition by adding quantitative particle-size thresholds and micronized-particle definitions, and optionally adding specified excipients/force control agents.
Two-fraction lactose particle distribution
A powder pharmaceutical composition comprising vardenafil hydrochloride as a PDE5 inhibitor, a first fraction of fine lactose particles, and a second fraction of lactose particles having an average diameter of about 5 μm to about 90 μm.
Controlled PDE5 inhibitor loading and fine-lactose amount
The PDE5 inhibitor is present in an amount of up to about 20% by weight relative to the total weight of the overall pharmaceutical composition, and the first fraction of fine lactose particles is present in an amount of up to about 10% by weight relative to the total weight of the lactose in the composition.
Fine lactose particle size upper limit
The first fraction of fine lactose particles has an average diameter of less than about 7 μm.
Micronized PDE5 inhibitor particles
The PDE5 inhibitor (or its salt or ester) is present as micronized particles.
Micronized particle Dv50 upper bound
The Dv50 of the micronized particles is up to about 2 μm.
Optional excipients and force control agents
The composition further includes one or more specified excipients including calcium stearate, magnesium stearate, leucine or leucine derivatives, lecithin, human serum albumin, polylysine, polyarginine, or other force control agents.
Across the claim set, the coverage is centered on using vardenafil hydrochloride together with two lactose particle fractions defined by fine-lactose sizing and a coarse lactose average diameter range, while restricting PDE5 inhibitor and fine-lactose weight fractions. Additional dependent refinements narrow fine-lactose particle size, specify micronized PDE5 inhibitor particles, impose a Dv50 upper bound for the micronized particles, and optionally include enumerated excipients/force control agents.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?