Anil Kurian, MN1 and Benjamin Barankin, MD, FRCPC2

1 McMaster University, Hamilton, ON, Canada
2 Toronto Dermatology Centre, Toronto, ON, Canada

Introduction

For decades, physicians have relied on conventional delivery vehicles, such as creams and ointments, for the topical treatment of cutaneous skin conditions. However, patient dissatisfaction with older topical therapy delivery methods can result in reduced patient compliance and ultimately poor control of their skin condition. As such, newer delivery vehicles in dermatology are being developed to improve clinical efficacy, reduce side-effects, and ultimately improve patient adherence. Newer vehicles include gel, foam, and spray preparations. The newer topical delivery agents have the potential to limit the progression of cutaneous disorders requiring oral systemic therapy, which can expose the patient to greater risk for adverse side-effects than topical therapy alone.

Vehicle Selection

In determining the most appropriate topical treatment regime for various skin disorders, physicians must undertake patient-specific assessments, including disease severity, patient preference, skin type, formulation availability, and delivery vehicle considerations. Active agents are formulated in a variety of vehicles (Table 1) to address the possible combinations. In general, patients with drier skin may favour creams for their moisturizing effect, while those with oilier skin may prefer gels or solutions. In addition to ease of spreadability, the use of foams may be particularly well suited for application over larger areas and hair bearing sites.

Delivery VehicleProsCons
Creams
  • oil and water base makes it suitable for use on most skin areas
  • tend to be less irritating
  • emollient properties
  • most suitable for patients with dry or sensitive skin
  • may result in an oily feel due to thicker consistency
Foams
  • minimal residue after application
  • quick drying, ease of application, lack of fragrance
  • no difference in cost compared to cream/solution after controlling for body surface area (BSA)
  • spreads easily, especially helpful if treating larger BSA
  • leaves minimal residue on skin surface
  • small number of application site reactions (e.g., burning, stinging, pruritus)
Gels
  • contain high water content
  • cooling effect upon application
  • significant long-term efficacy compared to conventional treatments
  • fast onset of action, good safety profile, high patient satisfaction
  • burning, itching, dryness, irritation, peeling, or redness of skin (<1% of patients)
Lotions
  • can have either water or alcohol base
  • are the most versatile
  • can be used for all skin types
  • have a lighter feel, which patients prefer
  • preferred for treatment of large or hairy areas, or skin sites subject to chafing (e.g., axilla, foot, groin).
  • can cause skin irritation (e.g., burning and dryness)
Ointments
  • effective for patients with very dry skin
  • many are preservative-free
  • provides higher potency and greater drug penetration
  • effective on thickened skin lesions
  • insoluble in water, so are difficult to wash off
  • can be perceived by patients as being greasy or messy to apply
Shampoos
  • short contact application (about 15 minutes)
  • reduced side-effects
  • can be used for extended periods of time
  • high patient satisfaction, which may increase adherence and treatment efficacy
  • small number of cases with burning, skin atrophy, and telangiectasia
Solutions
  • easy to spread
  • leaves minimal residue
  • usually contains an alcohol base that can cause stinging or exacerbate dryness and irritation
Sprays
  • can treat large areas of affected skin (up to 15-20% BSA)
  • improved quality of life scores when compared with other formulations
  • few cases of erythema, scaling, dryness, stinging/burning, and lack of smoothness

Table 1: Pros/cons of some newer and conventional topical delivery vehicles used in dermatology

Some Newer Therapeutics with Advanced Delivery

Foams for Dermatoses

  • Steroid foam preparations are newer formulations that provide commonly prescribed topical steroids in a low residue vehicle1 for the treatment of steroid-responsive dermatoses (e.g., allergic reactions, atopic dermatitis, and psoriasis).
  • In Canada, desonide foam 0.05% is indicated for the treatment of mild to moderate atopic dermatitis in patients =1 year of age.
  • Foam formulations of corticosteroids offer cosmetic advantages over traditional topical vehicles (ointments and creams), including quality of life variables such as minimal residue after application, quick drying, ease of application, and no odour.
  • Other findings included that patients using foam preparations spent less time applying medication as compared with other forms of topicals, and that no significant difference in cost was found between foam and cream/solution after controlling for body surface area.2
  • In preliminary studies, steroid foams have also been shown to be more efficacious treatment vehicles by demonstrating more rapid penetration and greater total absorption than conventional delivery modes (i.e., lotions and creams).1
  • Additionally, foam formulations are also considered to have a better acceptability profile in patients, with a greater positive effect on quality of life, than traditional topical formulations.
  • These advantages may lead to improved compliance and efficacy of treatment. The most frequently reported adverse events with steroid foam preparations are application-site reactions, such as burning, stinging, or itching.
  • However, ethanol-free steroid foam formulations are also being developed to minimize side-effects.2

Gel for Acne

  • Many new topical acne formulations have aqueous-based gel vehicle delivery systems that do not contain alcohol and are suitable for use in all skin types.
  • A once-daily formulation of clindamycin 1% + benzoyl peroxide (BP) 5% in a gel vehicle improves absorption and cosmetic acceptability, and facilitates ease of use, especially over larger or hair-bearing areas.3
  • Recent study findings demonstrate that this fix-dose combination not only has the potential to inhibit antimicrobial resistance,4 but also to improve both treatment tolerability and safety.5
  • The nonmedicinal constituents in this anti-acne compound include both glycerin (humectant) and dimethicone (emollient) to reduce both epidermal barrier impairment and cutaneous irritation, and increase hydration.

Gel for Scalp Psoriasis

  • Calcipotriol 0.005% + betamethasone dipropionate 0.05% in a lipophilic gel is specially formulated for the treatment of scalp psoriasis.6
  • A study comparing this two-compound gel with calcipotriol alone was conducted and the proportion of patients with ‘clear’ or ‘minimal’ disease at week 8 was significantly greater in the gel group (68.6%) as compared to the group receiving calcipotriol monotherapy (31.4%).7 Additionally, the rate of improvement was more rapid and adverse events were less with the two-compound gel.
  • The results further showed that the two-compound scalp formulation demonstrated significant efficacy after only a 1 week period, with a faster onset of effect than either of the individual components in the same vehicle.

Spray for Psoriasis

  • All of the newer topical clobetasol propionate (CP) formulations produce clearing or near-clearing of psoriasis for a large proportion of patients within 2-4 weeks, with response, safety, and tolerability rates that are at least comparable to those observed with older topical CP ointments and creams.8
  • CP spray is the only CP 0.05% formulation currently approved for treatment up to 4 weeks for those moderate-to-severe plaque psoriasis patients whose benefit/risk ratio supports the additional 2 weeks of treatment.
  • Previous studies have indicated that the additional 2 weeks of therapy with CP spray greatly increased efficacy without adversely affecting the safety profile of the drug.9
  • The CP spray may have an important role in the treatment of large areas of affected skin (up to 15-20% body surface area), expanding the range of topical treatment in psoriasis patients and improving quality of life scores at the end of treatment when compared with other formulations.9

Conclusion

Patient dissatisfaction with traditional topical modes of delivery in dermatology have led to the recent introduction of newer delivery vehicle formulations to improve clinical efficacy, reduce side-effects, and better address and promote patient adherence. Newer therapeutic options formulated as gels, foams, sprays, and shampoos have shown to be clinically efficacious, while exhibiting a high degree of patient satisfaction associated with their use. The newer topical delivery agents will also likely reduce the number of patients prematurely progressing to oral systemic therapies to control their cutaneous conditions, which can pose a more adverse side-effect profile than topical therapy alone.

References

  1. Reid DC, et al. Expert Opin Pharmacother 6(10):1735-40 (2005 Aug).
  2. Stein L. J Am Acad Dermatol 53(1 Suppl 1):S39-49 (2005 Jul).
  3. Tan JK. Skin Therapy Lett 7(5):1-2 (2002 May).
  4. Jackson JM, et al. J Drugs Dermatol 9(2):131-6 (2010 Feb).
  5. Zouboulis CC, et al. Cutis 84(4):223-9 (2009 Oct).
  6. Guenther LC. Skin Therapy Lett 14(4):1-4 (2009 May).
  7. Kragballe K, et al. Br J Dermatol 161(1):159-66 (2009 Jul).
  8. Feldman SR, et al. Am J Clin Dermatol 10(6):397-406 (2009).
  9. Mraz S, et al. J Dermatolog Treat 19(6):354-9 (2008).