Dry powder treprostinil for the treatment of pulmonary hypertension
Inventors
Roscigno, Robert Frank • Farrer, Brian T. • Sprague, Jacob J. • Maynor, Benjamin
Assignees
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Publication Number
US-10898494-B2
Publication Date
2021-01-26
Expiration Date
Abstract
A dry powder inhalation treatment for pulmonary arterial hypertension includes a dose of dry particles comprising greater than 25 micrograms of treprostinil enclosed in a capsule. The dry particles can include treprostinil, a wetting agent, a hydrophobicity modifying agent, a pH modifying agent and a buffer. A method of treating a patient having pulmonary arterial hypertension includes providing a patient a dry powder inhaler, providing the patient at least one capsule for use in the dry powder inhaler, the capsule including at least 25 micrograms of treprostinil.
Core Innovation
The invention concerns a dry powder composition comprising treprostinil or a pharmaceutically acceptable salt thereof for treatment of pulmonary hypertension, including pulmonary arterial hypertension, by inhalation using a dry powder inhaler. The formulation provides treprostinil as capsule-delivered dry particles with controlled aerodynamic properties and uniform particles.
The dry powder particles comprise a non-reducing sugar, trehalose, a wetting agent, polysorbate 80, a hydrophobicity modifying agent, L-leucine, a pH modifying agent, sodium citrate, and a buffer, sodium chloride. The invention uses these components to form molded dry particles suitable for dry powder inhaler dosing.
The invention also describes breath-count based administration over one to four breaths and, in another approach, four to sixteen breaths for total daily dosing. Early formulation characterization using aerodynamic size and fine particle fraction is described, together with extensive excipient and treprostinil dose ranges that map to tested dose levels in clinical and nonclinical studies.
Claims Coverage
The independent claims are clm-00001, clm-00010, clm-00012, and clm-00013. Across these claims, the inventive features center on treating pulmonary hypertension with treprostinil dry powder compositions delivered by a dry powder inhaler over defined breath ranges and particle configurations, including specific excipient classes and a uniform-particle higher daily dose approach.
Breath-delivered treprostinil dry powder for pulmonary hypertension
Administration of a dry powder composition comprising from about 100 micrograms to about 300 micrograms treprostinil or a pharmaceutically acceptable salt thereof to a patient by inhalation using a dry powder inhaler over one to four breaths to treat pulmonary hypertension.
Capsule- and inhaler-based treprostinil dry powder with excipient classes
Providing a patient a dry powder inhaler; providing the patient at least one capsule for use in the dry powder inhaler, wherein the at least one capsule contains a dry powder composition comprising at least 100 micrograms of treprostinil, a non-reducing sugar, a wetting agent, a hydrophobicity modifying agent, a pH modifying agent and a buffer; and instructing the patient to utilize the dry powder inhaler to inhale the dry powder composition from each capsule in one to two breaths.
Particle-configured treprostinil dry powder dose over defined breaths
Dosing the patient having pulmonary hypertension with a dry powder dose of treprostinil, wherein the dose of treprostinil is from about 100 micrograms to about 300 micrograms and delivered over one to four breaths, wherein the dry powder dose is configured into particles, wherein each particle comprises the treprostinil, a non-reducing sugar, a wetting agent, a hydrophobicity modifying agent, a pH modifying agent and a buffer.
Uniform-particle treprostinil dry powder delivered over four to sixteen breaths
Administering a dry powder composition comprising between about 400 micrograms treprostinil and about 1200 micrograms treprostinil to a patient over a day through four to sixteen breaths to treat pulmonary hypertension, wherein the dry powder composition is configured as uniform particles.
Collectively, the independent claims require treating pulmonary hypertension with treprostinil dry powder delivered by a dry powder inhaler over specified breath ranges, with the dry powder configured as particles, including uniform particles in one claim, that include specific excipient classes.
Stated Advantages
Improved usability versus nebulized treprostinil.
Fewer side effects than a nebulized dose of 54 micrograms of treprostinil.
Documented Applications
Treatment of pulmonary hypertension/pulmonary arterial hypertension (PAH) in a patient using dry powder inhalation with treprostinil delivered from capsules through a dry powder inhaler.
Use of a dry powder inhaler and capsules configured with molded dry particles for inhalation over one to four breaths, and in other ranges over four to sixteen breaths.
Example device use is described as RS00 Model 8 dry powder inhalation device, with HPMC capsule size 3.
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