The original hydroethanolic foam formulations to reach the market represented the culmination of many years of research. In fact, studies on corticosteroid foam formulations date back to the 1970s,36 but foam formulations did not reach the market until 2000. Like aerosol sprays, aerosol foams fit the “Other” category of topical dosage forms.
Foam formulations tend to be user-friendly and elegant for use in treating scalp dermatoses. Compared to traditional clobetasol propionate solution, Olux (clobetasol propionate 0.05%, Stiefel/GlaxoSmithKline) was shown to provide enhanced absorption of clobetasol propionate in cadaver skin.37 Enhanced absorption may be attributable to the fact that the foam creates a super-saturated solution when applied to the skin. When the propellants and alcohols—constituting a significant proportion of the formulation— evaporate, the resulting solution left on the skin may have up to a 10-fold higher concentration of active drug compared to the initially dispensed foam. The tremendous resulting gradient creates a driving force that delivers the drug through the stratum corneum.
The rapid absorption of active drug from the foam vehicles is demonstrated through comparison of pharmacodynamic profiles of hydroethanolic foams compared to other vehicles. In trials comparing absorption of betamethasone valerate from Luxiq (betamethasone valerate 0.12%, Stiefel/ GlaxoSmithKline) foam to betamethasone 0.1 lotion, foam provided nearly six-times the rate of absorption of betamethasone as the lotion. The peak rate of absorption for the lotion at 35 hours was similar to the rate of absorption for the foam at 2.5 hours.38 This rapid absorption may be of clinical benefit. In actual use, very little of any topically applied formulation would be expected to remain on the skin at four or six hours, thus reducing the total amount of drug actually delivered to the site of treatment. Foams appear to obviate those concerns.
The hydroethanolic foam was originally designed and proposed for use on hair bearing areas, and engineered so as not to leave any residue on hairy areas; the nonvolatile components left on the skin are quickly absorbed and do not crystallize.
Although patients rated their experience with hydroethanolic foams favorably in clinical trials, and the incidence of adverse events was low, these formulations were associated with potential application site stinging and burning.39 To address these issues, triphasic emollient foams—consisting of oil, water, and organic solvent— were developed (VersaFoam EF).
As the name suggests, emollient foams contain petrolatum and long-chain fatty acids that lay on the skin to create physical barriers to transepidermal water loss. The foams are thermolabile. The alcohols maintain the structure of the foam at room temperature, but at about 88 or 90 degrees, the lattice collapses and the alcohol evaporates. The active drug is solublized along with the emollient components in the residue of the vehicle. Evidence suggests that components of the formulation, likely alcohol, serve as penetration enhancers to facilitate rapid drug delivery across the skin membrane via the intracellular route.40
Verdeso foam (desonide 0.05%, Stiefel/GlaxoSmithKline) has a similar emollient foam formulation that spreads easily and, as indicated in the package insert, is associated with minimal local application site burning and stinging.
The newest foam vehicle formulation to come to market, Extina (ketoconazole 2%, Stiefel/GlaxoSmithKline), was designed to facilitate treatment of seborrheic dermatitis, which frequently occurs in hair-bearing areas. In trials comparing ketoconazole 2% foam to vehicle foam, ketaconazole 2% cream, or cream vehicle, ketoconazole 2% foam provided a more rapid onset of action compared to active cream, as demonstrated by two-week pruritus and 2-grade+ improvement from baseline scores. With the exception of stinging, likely attributable to ethanol in the foam vehicle, ketaconazole foam had similar rates of other adverse events compared to ketoconazole cream or vehicle cream.41
Sides Media.