Method for reducing side effects from administration of phosphodiesterase-4 inhibitors
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Publication Number
US-12685727-B2
Publication Date
2026-07-21
Expiration Date
Abstract
A method for altering the PK profile of a pharmaceutical formulation containing a PDE-4 inhibitor, such as roflumilast, to reduce the spike in Cmax. The spike in Cmax is reduced by topically administering the PDE-4 inhibitor in combination with one or more phosphate ester surfactants. Reducing the spike in Cmax will reduce gastrointestinal side effects and result in better patient compliance.
Core Innovation
The invention describes topical cream formulations containing the PDE-4 inhibitor roflumilast and phosphate ester surfactants, including dicetyl phosphate and ceteth-10 phosphate, for treating inflammatory dermatosis. The claims center on a cream comprising roflumilast, diethylene glycol monoethyl ether, and an emulsifier blend comprising cetostearyl alcohol and those phosphate esters. The background section is not included in the provided content, so the problem it identifies is not explicitly described in patent.
The described formulation slows roflumilast absorption, reduces Cmax peaks, maintains systemic exposure, and produces a flatter steady-state profile with relatively stable 24-hour plasma concentrations after 28 days. In a reported phase 1/2a plaque-psoriasis study, roflumilast cream improves target-plaque severity-area endpoints compared with vehicle. The treatment is described as generally well tolerated, with no reported diarrhea or vomiting in the study.
Claims Coverage
The two independent claims cover two inventive features directed to the topical treatment of inflammatory dermatosis using the specified roflumilast cream.
Topical roflumilast cream with a reduced peak-to-trough ratio
A method of treating inflammatory dermatosis by topical administration of a cream comprising roflumilast, diethylene glycol monoethyl ether, and an emulsifier blend comprising cetostearyl alcohol, dicetyl phosphate, and ceteth-10 phosphate, wherein the roflumilast blood-plasma peak-to-trough ratio is reduced to below 2 after four weeks. [procedural detail omitted for safety]
Topical roflumilast cream with reduced Cmax
A method of treating inflammatory dermatosis by topical administration of a cream comprising roflumilast, diethylene glycol monoethyl ether, and an emulsifier blend comprising cetostearyl alcohol, dicetyl phosphate, and ceteth-10 phosphate, wherein roflumilast Cmax is reduced relative to an oral roflumilast formulation marketed under the trademark DALIRESP. [procedural detail omitted for safety]
The independent claims cover the specified topical roflumilast cream in methods for treating inflammatory dermatosis, distinguished by pharmacokinetic outcomes of a reduced peak-to-trough ratio below 2 or reduced Cmax relative to oral roflumilast.
Stated Advantages
The formulation slows absorption, reduces Cmax peaks, maintains systemic exposure, and produces a flatter steady-state profile with relatively stable 24-hour plasma concentrations after 28 days.
In the reported plaque-psoriasis study, roflumilast creams improve target-plaque severity-area endpoints, including TPSS, TPA, and TPSS-TPA scores relative to vehicle.
Treatment is generally well tolerated, with no reported diarrhea or vomiting.
The claims specify a roflumilast blood-plasma peak-to-trough ratio below 2 after four weeks or a Cmax reduced relative to oral DALIRESP.
Documented Applications
Topical treatment of inflammatory dermatosis, including atopic dermatitis and psoriasis as identified in the dependent claims.
Evaluation of roflumilast cream in a phase 1/2a study for plaque psoriasis.
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