Advances in Retinoid Formulation

Topical retinoids are first-line therapy for the treatment of all types of acne. These agents may be used as monotherapy for mild comedonal acne or as part of a combination regimen for other forms of the disease.

Retinoids exert several effects on the skin. They reduce inflammation, promote collagen production, and normalize the follicular hyperkeratinization that leads to comedone formation. Tazarotene is a third-generation retinoid that is selective for the RAR-β and RAR-γ subtypes. It is a prodrug that is rapidly converted to its active form, tazarotenic acid, in the skin.

Addressing Irritation

While they are effective, topical retinoid use is limited by potential skin irritation, especially during the first two to four weeks as the skin undergoes a retinization period and adjusts to use of the retinoid. This irritation is caused by topical retinoids disturbing corneocyte cohesion and contributing to barrier disruption. The skin may develop dryness, redness, burning, stinging, and peeling.

A variety of treatment strategies have been employed to reduce potential retinoid irritation. Concurrent use of moisturizers, intermittent application, and dilution of the drug in a moisturizer before application are tactics commonly used by patients. It is important for patients to stick to their regimen, because non-adherence, even as a result of side effects, ultimately results in poor outcomes.

The Latest Option

Arazlo lotion (tazarotene 0.045%, Ortho Dermatologics) was FDA approved in December 2019 for the topical treatment of acne vulgaris in patients aged nine or older. It is the first tazarotene-based acne treatment available in lotion form, with proven efficacy and favorable tolerability. Arazlo lotion is formulated with a patented polymeric emulsion technology that enhances penetration and minimizes cutaneous side effects.¹ Tazarotene and moisturizing ingredients (light mineral oil, diethyl sebacate) are solubilized within oil droplets, evenly dispersed throughout the formula using a honeycomb mesh technology. This allows for the simultaneous delivery of tazarotene and moisturizing ingredients and results in improved cutaneous tolerance of the retinoid. In one study, 93 percent of patients who used the vehicle alone agreed that it left their skin feeling more moisturized and hydrated than what they were currently using.²

The FDA approval for Arazlo was based on data from two Phase 3 multicenter, randomized, double-blind, vehicle-controlled clinical trials comprising 1,614 patients with moderate to severe acne. In both studies, all primary efficacy endpoints were met with statistical significance (p<0.001), and the drug was generally well-tolerated in the clinical study population.³

In a Phase 2, head-to-head study, Arazlo and Tazorac (tazarotene) Cream 0.1% showed similar treatment success rates and similar reductions in both inflammatory and non-inflammatory lesions over 12 weeks. Arazlo was associated with about half the number of adverse events and fewer treatment-related adverse events than Tazorac.⁴

Change Agent

Advances in formulation technology are allowing for better delivery, stability, and tolerability of many of the active ingredients we have used in the past. However, this is much more than wine in a new bottle. When the bottle has improved so much, it truly changes the wine as well. The same can be said for tazarotene. In this novel polymeric emulsion, Arazlo lotion changes the way that tazarotene interacts with the skin, minimizing potential adverse events and improving outcomes.

1.Tanghetti EA, et al. Optimized formulation for topical application of a fixed combination halobetasol/tazarotene lotion using polymeric emulsion technology J Dermatol Treat. 2019. Sep 26:1-8. doi: 10.1080/09546634.2019.1668907

2.Company data on file

3.Tanghetti EA, et al. Tazarotene 0.045% Lotion for Once-Daily Treatment of Moderate-to-Severe Acne Vulgaris: Results from Two Phase 3 Trials. J Drugs Dermatol. 2020;19(1): doi:10.36849/JDD.2020.3977.

4. Tanghetti EA , et. Al. A Phase 2 multicenter, double-blind, randomized, vehicle- controlled clinical study to compare the safety and efficacy of a novel tazarotene 0.045% lotion and tazarotene 0.1% cream in the treatment of moderate-to-severe acne vulgaris. J Drugs Dermatol. 2019;18(6):542-548.