Roflumilast formulations with an improved pharmacokinetic profile
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12016848-B2
Publication Date
2024-06-25
Expiration Date
Abstract
An improved a method of treating a patient having a disorder responsive to PDE-4 inhibition by administering roflumilast. The improvement involves administering the roflumilast topically in a composition having a roflumilast release profile that produces in the patient a flattened plasma concentration time curve and a reduced Cmax relative to oral administration of a PDE4-inhibiting amount of roflumilast. Such disorders include inflammatory disorders such as inflammatory dermatoses, including psoriasis, atopic dermatitis and seborrheic dermatitis. Such disorders also include inflammatory diseases in a variety of organs, especially the lungs (asthma, COPD). Because of reduced side effects with topical administration due to the improved pharmacokinetics (PK) characteristics, it may be possible to provide higher systemic exposures (AUCs) with topical administration, resulting in greater therapeutic efficacy than with the oral route of administration.
Core Innovation
The claim describes a topical roflumilast pharmaceutical composition formulated as an emulsion. The composition comprises roflumilast in an amount of 0.05–1.0% w/w, water, a hydrophobic component, a solvent comprising diethylene glycol monoethyl ether, and a surfactant. Following administration, the composition produces a plasma concentration-time curve with a delayed Tmax relative to oral administration of roflumilast, providing gradual absorption and reduced Cmax spikes.
The disclosure reports plasma concentration profile comparisons for topical roflumilast formulations, including ARQ-151, roflumilast N-oxide, and comparator profiles. Sustained exposure is demonstrated in preclinical comparisons and in a psoriasis study showing plaque improvement over four weeks. Additionally, hexylene glycol inhibits crystal growth and particle-size changes within the formulation.
Claims Coverage
The claims coverage identifies two inventive features within the independent claim directed to the topical roflumilast emulsion composition.
Topical roflumilast emulsion composition
A topical roflumilast pharmaceutical composition comprising roflumilast in an amount of 0.05–1.0% w/w, water, a hydrophobic component, a solvent comprising diethylene glycol monoethyl ether, and a surfactant, wherein the composition is an emulsion.
Delayed Tmax absorption profile
The topical roflumilast composition has an absorption profile that produces in a patient following administration a plasma concentration-time curve having a delayed Tmax relative to oral administration of roflumilast.
The independent claim combines the specified topical roflumilast emulsion formulation with an absorption profile that provides a delayed plasma Tmax relative to oral administration.
Stated Advantages
The topical formulation is associated with gradual absorption, reduced Cmax spikes, and a flatter plasma concentration-time profile than oral roflumilast.
Hexylene glycol inhibits crystal growth and particle-size changes.
The psoriasis study reports significant plaque improvement with the creams versus vehicle after four weeks.
Documented Applications
Topical administration of the roflumilast pharmaceutical emulsion composition to a patient.
Evaluation in a psoriasis study for plaque improvement using topical roflumilast creams.
Interested in licensing this patent?