Topical 5% Spironolactone Gel Versus 0.1% Adapalene Gel for Acne Vulgaris: A Randomized Split-Face Study

Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit that affects a large proportion of adolescents and young adults worldwide. The condition is characterized by the development of comedones, papules, pustules, and in severe cases nodules and cysts. The pathogenesis of acne involves multiple mechanisms including follicular hyperkeratinization, excessive sebum production stimulated by androgens, colonization with Cutibacterium acnes, and inflammatory responses within the pilosebaceous unit.

Topical retinoids are considered a cornerstone in the management of acne vulgaris due to their comedolytic and anti-inflammatory properties. Adapalene, a third-generation topical retinoid, is commonly used because of its efficacy and relatively favorable tolerability profile. Despite these advantages, some patients experience skin irritation, dryness, and erythema, which may limit adherence and treatment outcomes.

Spironolactone is an antiandrogen medication traditionally used orally for the treatment of hormonal acne, particularly in females. It acts by blocking androgen receptors and reducing sebaceous gland activity, thereby decreasing sebum production. However, systemic administration may be associated with potential adverse effects. Topical formulations of spironolactone have been proposed as an alternative approach to deliver antiandrogen effects locally while minimizing systemic exposure.

Recent advances in pharmaceutical technology, including nano-formulation delivery systems, may enhance the penetration and stability of topical medications and improve therapeutic outcomes. A topical 5% spironolactone gel nano-formulation may provide improved skin penetration and targeted delivery to the pilosebaceous unit.

The present study is designed as a split-face comparative clinical study to evaluate the efficacy and safety of topical 5% spironolactone gel nano-formulation compared with topical 0.1% adapalene gel in patients with acne vulgaris. In this design, each participant will apply spironolactone gel to one side of the face and adapalene gel to the other side according to the study protocol. This approach allows direct comparison of the two treatments within the same individual and minimizes inter-individual variability.

Eligible participants diagnosed with acne vulgaris will be recruited from dermatology clinics. Baseline clinical assessment will include evaluation of acne severity, lesion counts, and skin examination. Participants will receive instructions regarding the application of each topical treatment and follow-up visits will be scheduled throughout the study period to monitor treatment response and detect possible adverse events.

The primary outcome will be the change in acne lesion counts and clinical severity after the treatment period. Secondary outcomes will include evaluation of treatment tolerability, improvement in inflammatory and non-inflammatory lesions, and documentation of local adverse reactions such as erythema, dryness, burning sensation, or irritation.

The findings of this study may contribute to the growing body of evidence regarding topical antiandrogen therapy for acne and may support the use of spironolactone nano-formulation as an effective and safe topical treatment option for patients with acne vulgaris.

Inclusion criteria

Age: 18-45 years old.

• Patients with mild to moderate bilateral acne vulgaris on the face.
• Presence of non-inflammatory acne (open and closed comedones).
• Presence of inflammatory papules and pustules.

Exclusion criteria

• Pregnancy and lactation.
• Patients taking oral contraceptive pills or any hormonal treatment.
• Patients who were using topical or systemic medications for acne in the last two months prior to starting therapy.
• Patients who had received laser resurfacing, chemical peeling, mesotherapy, or any similar facial interventions.