Abstract: Roflumilast crystals have been shown to increase in size during storage. The size of the roflumilast crystals can affect the bioavailability and efficacy of a pharmaceutical composition. The growth of roflumilast crystals can be inhibited during storage by including hexylene glycol in the composition. The resulting composition has improved bioavailability and efficacy and can be used to inhibit phosphodiesterase 4 in a patient in need of such treatment.

Abstract: The disclosure relates to stable topical pharmaceutical compositions of SHR0302 (also known as ARQ-250). In certain embodiments, pharmaceutical compositions of SHR0302 having a pH of less than about 4.6 have improved stability and do not exhibit crystal formation of the API. In certain embodiments, pharmaceutical compositions of SHR0302 comprising about 20% to about 30% dimethyl sulfoxide (DMSO) have improved stability and do not exhibit crystal formation of the API. The improved formulations of SHR0302 can exhibit acceptable commercial product shelf life and do not exhibit loss of potency of the API after prolonged storage.

Abstract: Methods of treating a skin disorder or condition, including psoriasis, atopic dermatitis, and seborrheic dermatitis, in a patient by topically administering to the patient a pharmaceutical composition comprising roflumilast. The methods rapidly (e.g., within 24 or 48 hours) reduce itch experienced by a patient, for example itch as measured by the Worst Itch Numerical Rating Scale (WI-NRS). The method can also reduce itch as measured by the WI-NRS by 4 or more points.

Abstract: Methods of treating a skin disorder or condition, including psoriasis, atopic dermatitis, and seborrheic dermatitis, in a patient by topically administering to the patient a pharmaceutical composition comprising roflumilast. The methods rapidly (e.g., within 24 or 48 hours) reduce itch experienced by a patient, for example itch as measured by the Worst Itch Numerical Rating Scale (WI-NRS). The method can also reduce itch as measured by the WI-NRS by 4 or more points.

Abstract: Methods of treating a skin disorder or condition in a patient by topically administering to the patient a pharmaceutical composition comprising roflumilast. The methods of treatment include administering the roflumilast composition once a day for a period of time followed by administering the roflumilast composition twice weekly as a maintenance dosing regimen.

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.

Abstract: An improved method is provided for 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.

Abstract: The disclosure relates to stable topical pharmaceutical compositions of SHR0302 (also known as ARQ-250). In certain embodiments, pharmaceutical compositions of SHR0302 having a pH of less than about 4.6 have improved stability and do not exhibit crystal formation of the API. In certain embodiments, pharmaceutical compositions of SHR0302 comprising about 20% to about 30% dimethyl sulfoxide (DMSO) have improved stability and do not exhibit crystal formation of the API. The improved formulations of SHR0302 can exhibit acceptable commercial product shelf life and do not exhibit loss of potency of the API after prolonged storage.

Abstract: The present invention is a method and composition comprising laureth-4 in topical formulations, wherein the laureth-4 increases the penetration of active ingredients across the skin. In a particularly preferred embodiment, the active ingredient is SHR0302.

Abstract: Pharmaceutical compositions for the topical administration of a drug to the pilosebaceous unit and methods for administering the same. As disclosed herein, the inventors of the present invention have made the surprising discovery that pharmaceutical compositions comprising small particles of an active pharmaceutical ingredient can be administered to the pilosebaceous unit. The pharmaceutical composition can comprise SHR0302 or spironolactone as an active pharmaceutical ingredient.

Abstract: The present invention is a method and composition for the treatment of skin conditions where the epidermal barrier has decreased function such as when the patient is suffering from eczema, in particular, Atopic Dermatitis. Epidermal barrier function can be significantly improved and the extraction of epidermal lipids can be reduced by using formulations containing high Krafft temperature surfactants, preferably, anionic surfactants.

Abstract: Topical pharmaceutical compositions comprising roflumilast and solvents that are capable of dissolving high amounts of roflumilast. The pharmaceutical compositions are capable of dissolving high amounts of roflumilast relative to other commonly used solvents in approved topical pharmaceutical compositions. The solvents are particularly useful when combined with water to maintain high levels of dissolved roflumilast, which is highly insoluble in water.

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.

Abstract: An improved method is provided for 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.

Abstract: Roflumilast crystals have been shown to increase in size during storage. The size of the roflumilast crystals can affect the bioavailability and efficacy of a pharmaceutical composition. The growth of roflumilast crystals can be inhibited during storage by including hexylene glycol in the composition. The resulting composition has improved bioavailability and efficacy and can be used to inhibit phosphodiesterase 4 in patient in need of such treatment.

Abstract: The present invention is a method and composition comprising laureth-4 in topical formulations, wherein the laureth-4 increases the penetration of active ingredients across the skin. In a particularly preferred embodiment, the active ingredient is SHR0302.

Abstract: The present invention is directed to methods for improving the therapeutic outcome of treatment with roflumilast. The therapeutic outcome is improved by consistent delivery and/or a longer plasma half-life of a topically administered roflumilast composition. The roflumilast composition preferably includes dicetyl phosphate, ceteth-10 phosphate, diethylene glycol I monoethyl ether, and/or hexylene glycol.

Abstract: The present invention is a method and composition for the treatment of skin conditions where the epidermal barrier has decreased function such as when the patient is suffering from eczema, in particular, Atopic Dermatitis. Epidermal barrier function can be significantly improved and the extraction of epidermal lipids can be reduced by using formulations containing high Krafft temperature surfactants, preferably, anionic surfactants.

Abstract: Pharmaceutical compositions for the topical administration of a drug to the pilosebaceous unit and methods for administering the same. As disclosed herein, the inventors of the present invention have made the surprising discovery that pharmaceutical compositions comprising small particles of an active pharmaceutical ingredient can be administered to the pilosebaceous unit. The pharmaceutical composition can comprise SHR0302 or spironolactone as an active pharmaceutical ingredient.

Abstract: Decreasing skin penetration lag times will improve the bioavailability of a topically administered roflumilast composition. A shorter skin penetration lag time provides quicker onset of disease relief and more consistent bioavailability as there is less transference to clothing or other people. The skin penetration lag time for roflumilast can be reduced by formulating a roflumilast composition to have a pH between 4.0-6.5 and/or combining roflumilast with an emulsifier blend comprising cetearyl alcohol, dicetyl phosphate and ceteth-10 phosphate.