Method and formulation for improving roflumilast skin penetration lag time

Inventors

Osborne, David W.

Assignees

Arcutis Biotherapeutics Inc

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.

Core Innovation

The invention relates to topical administration of roflumilast to reduce roflumilast skin penetration lag time in a patient. It provides roflumilast compositions formulated with diethylene glycol monoethyl ether and an emulsifier blend comprising cetearyl alcohol, dicetyl phosphate and ceteth-10 phosphate, with the composition having a pH between 4.0 and 6.5. The roflumilast is present in an amount of 0.005-2% w/w in the stated compositions, and the compositions do not include hexylene glycol.

The invention addresses the problem that roflumilast shows skin penetration lag time, and that a lag time may limit onset when administered topically. In living mammal studies described in the partial content, emulsifier and pH are stated to unexpectedly shorten roflumilast skin penetration lag time.

Formulation approaches described include using a pH of about 4.0-6.5 and selecting an emulsifier blend with cetearyl alcohol, dicetyl phosphate and ceteth-10 phosphate. Example results in the partial content report that formulations with the specified pH range achieve skin penetration lag time of less than 1 hour, and additional example observations state that CES-containing creams yield measurable receptor levels at about 1 hour in excised human skin.

Claims Coverage

The provided independent claims are clm-00001 and clm-00006. Together they define multiple formulation components and physicochemical constraints intended to reduce roflumilast skin penetration lag time in a patient, with a key inventive focus on using a specified emulsifier blend and a specified pH range while excluding hexylene glycol.

The independent claim set defines topical methods that reduce roflumilast skin penetration lag time by using a specified emulsifier blend (cetearyl alcohol/dicetyl phosphate/ceteth-10 phosphate), a composition pH between 4.0-6.5, roflumilast at 0.005-2% w/w, and an explicit exclusion of hexylene glycol, with further formulation coverage including diethylene glycol monoethyl ether and, in one independent claim, isopropyl palmitate. The performance constraint includes skin penetration lag time of less than 60 minutes, and the method targets psoriasis or atopic dermatitis.

Stated Advantages

Documented Applications