Innovation in delivery of a topical combination treatment (enstilar®) for psoriasis vulgaris

Enstilar® foam spray (calcipotriol 50 microgram/g plus betamethasone dipropionate 500microgram/g) was recently approved in the US and in Europe for the topical treatment of psoriasis. Enstilar® has demonstrated improved clinical efficacy compared to other formulations of Cal/BD1.
The propellants of Enstilar® act as a solvent for the active pharmaceutical ingredients (APIs), evaporate rapidly upon application, leaving fully dissolved supersaturated APIs available for skin penetration.
The properties of a topical formulation are important for patient preference as well as drug delivery. Skin penetration of the API is proportional to the concentration of dissolved API on the skin. Supersaturation of API is known to improve skin penetration 2.
A novel approach was undertaken to investigate if supersaturation offers an explanation for the enhanced efficacy seen with Enstilar® spray foam.
Microscopy (200x), X-Ray Powder Diffraction (XRPD) and Raman-imaging was used to identify any crystalline particles of Cal/BD in foam and ointment, when applied and 18 hours after application no Cal/BD crystals could be identified in the foam. Microscopy and Raman identified Cal/BD crystals in the ointment. XRPD identified BD but not Cal crystals in ointment.
This study documents that the enhanced local bioavailability of Cal/BD in the foam spray vehicle results from supersaturation, a potential explanation for the improved clinical efficacy observed in clinical trials.
1. Paul et al; EADV 2015; Copenhagen, Denmark; Poster P1724
2. Cilurzo et al; Curr Pharm Design 2015;21(20):2733-44.

Mr Kasper Nørremark