Topical Vehicle Formulations in the Treatment of Acne

adherence is directly related to poor treatment outcomes and patient dissatisfaction. A common cause of non-adherence is local cutaneous irritation, due to either the ingredients in the vehicle or the active drug itself.⁵ As we review the current treatments for acne, it should be noted that the goals of formulations are as follows: reduce irritation, enhance therapeutic outcome, and promote patient adherence.^6,7 These goals can be accomplished by reducing the concentration of the active drug, delayed release of the active drug, and adding other ingredients to the formulation vehicle to repair the damaged epidermal barrier and offset the irritating effects of the drug.³Vehicles and Acne TherapyAcne is a complex and chronic skin disease that commonly affects adolescents and adults. The etiology is multifactorial and the pathogenesis likely involves hormonal function, increased sebum production, follicular hyperkeratinization, proliferation of Propionibacterium acnes (P. acnes), and the propagation of various inflammatory cascades.^8,9 In fact, inflammation can persist throughout the course of lesion development and resolution, as evidenced by persistent inflammatory hyperpigmentation and erythema.⁹ Given that acne is a chronic disease with a negative impact on psychosocial function and quality of life at all stages in the acne lesion cycle, it is critical to initiate effective therapy as early as possible to provide better treatment outcomes.However, as described above, designing acne drug formulations is a complex and multifaceted process. Combination therapy is often required to address the different pathophysiologic associations with acne. This is challenged by the need to address the subsequent adverse events associated with the formulations, such as irritation and dryness. Fixed combination formulations for acne have simplified therapeutic decisions with once-a-day application, leading to improved adherence.⁵ New formulations and delivery techniques, like microspheres and hydrating bases, have also been implemented to help reduce irritation, attributing to greater patient satisfaction.Common Acne TherapiesTopical treatment is the mainstay of acne therapy. The most commonly prescribed topical medications for acne include benzoyl peroxide, clindamycin, and retinoids.¹⁰ Despite their effectiveness in treating mild to moderate acne vulgaris, these topical medications are found to be irritating, and are historically associated with poor tolerability and diminished patient adherence.^6,7 Current guidelines for treating acne vulgaris emphasize using both topical retinoids and benzoyl peroxide for maintenance therapy.⁷Benzoyl peroxide (BPO) is a major workhorse in the treatment of acne. It is classified as a non-antibiotic antibacterial agent that is bactericidal against P. acnes due to its potent oxidizing activity.11,12 It is effective against inflammatory and non-inflammatory lesions; however many benzoyl peroxide preparations are limited by their adverse events of dryness and irritation. Given the development of bacterial resistance to P. acnes, the utility of benzoyl peroxide has increased because P. acnes has not yet developed resistance to topical benzoyl peroxide.¹³ As a result, BPO is often used in conjunction with both topical and systemic antibiotics, such as topical clindamycin, to reduce the development of P. acnes resistance.¹²Antibiotic sensitivities to P. acnes arose in the 1980s with the introduction of topical formulations of erythromycin and clindamycin.¹⁴ Clindamycin is a bacteriostatic agent for P. acnes and also exhibits anti-inflammatory activities.11,15 Both BPO and clindamycin are currently the most widely prescribed antimicrobials for the treatment of acne, and they are even more effective when combined.^16,17 In a clinical trial comparing combination clindamycin phosphate 1% and benzoyl peroxide 5% gel formulation with matching clindamycin 1% gel monotherapy, total P. acnes count and clindamycin-resistant P. acnes count were significantly reduced after 16 weeks of treatment with the use of combination gel as compared to clindamycin alone. Moreover, in the group using the combination gel, the reduction in total P. acnes and clindamycin resistance P. acnes counts correlated with a reduction in total acne lesions.¹⁷Current guidelines also emphasize the use of topical retinoids for treatment and maintenance therapy of mild to moderate acne vulgaris.⁷ The mechanism of action of topical retinoids is anti-comedolytic; they regulate keratinization and target the microcomedone to reduce the formation of new acne lesions and can significantly interrupt disease progression.18 Similarly to combination antimicrobial treatments, combination retinoid and BPO treatments have also been developed in recent years. In accordance with the general goals of topical formulations used in acne, the aim of combination retinoids/BPO formulations is to reduce irritation, enhance therapeutic outcomes and promote patient adherence.⁶ This has been done by reducing the concentration of active drug, providing for delayed release of the active drug, or incorporating ingredients into the formulation vehicle that repairs the impaired epidermal barrier and offsets the irritating effect of the drugs.⁵Minimizing irritation with BPO and TretinoinHydrophase Base FormulationsBenzoyl peroxide 4% in a hydrophase base and benzoyl peroxide 8% in a hydrophase base are both topical preparations that come in the form of a creamy wash and a gel. The hydrophase formulation is thought to reduce the irritation associated with the use of benzoyl peroxide.¹¹ Both the wash and the gel preparations are indicated for use in mild to moderate acne. They can be used as an adjunct with other acne treatment regimens, including antibiotics, retinoic acid products, and sulfur/salicyclic acid containing preparations.^11,19