Safety and Efficacy of Micronized Tretinoin Gel (0.05%) in Treating Adolescent Acne

June 2011 | Volume 10 | Issue 6 | Original Article | 647 | Copyright © June 2011

Helen M Torok MDa and Radhakrishan Pillai PhDb

aTrillium Creek Dermatology, Medina, OH bDow Pharmaceutical Sciences, Inc., Petaluma, CA

Abstract

Tretinoin is widely used in the treatment of acne. Despite significant advances in formulation development, irritation and dryness can be particularly bothersome, especially during the first 3-4 weeks, impacting adherence. Dose titration and adjunct use of moisturizers have been commonly employed. Co-prescribing with benzoyl peroxide (BPO) or a BPO/antibiotic combination is also common practice. The tretinoin molecule is unstable and can be degraded by BPO, further complicating treatment regimens.

Lately, formulation technology has focused on providing more efficient penetration of the tretinoin into the skin layers so that lower concentrations of tretinoin might afford better tolerability, but maintain good efficacy; incorporating moisturizing excipients to minimize irritation; and providing greater stability to the tretinoin molecule. This approach would be particularly relevant in a pediatric acne population where efficacy/tolerability balance is important and treatment regimens must take into account lifestyles, but little data exist on the use of tretinoin in this patient population.

A micronized formulation of tretinoin (0.05%) gel has been developed that provides a more efficient delivery of tretinoin, because of its optimal particle size, no degradation by BPO and better cutaneous tolerability than tretinoin microsphere (0.1%) gel without compromising efficacy in a pediatric population.

J Drugs Dermatol. 2011;10(6):647-652.

INTRODUCTION

Tretinoin is a widely used drug in the topical treatment of acne, photo-aged skin, psoriasis and other skin disorders. Originally approved by the U.S. Food and Drug Administration (FDA) in 1971 as a topical acne treatment, it improves acne by increasing the turnover of follicular epithelial cells, thus normalizing keratinization; extrusion of comedones ensues.1-3 Corneocyte shedding also accelerates, inhibiting the formation of new comedones.4,5
The first formulation of tretinoin consisted of a high concentration of active ingredient in a penetrating hydroalcoholic solution. Excessive skin irritation was common. Subsequently, tretinoin became available in cream and gel vehicles in a variety of concentrations, but irritation and dryness was still a major drawback in some patients and generally dose dependent.6 The cutaneous tolerability associated with the use of tretinoin led to the development of a number of new topical delivery systems; including the incorporation of large polymers into tretinoin formulations and incorporating tretinoin itself into microspheres.
Including large polymers in tretinoin formulations was based on the concept that tretinoin irritation may be reduced if the drug is prevented from migrating into deeper layers of the epidermis. Indeed, patch test studies show that tretinoin cream and gel formulations containing polyolprepolymer-2 produce less irritation than do the formulations without the large polymer.7
Encapsulating tretinoin molecules in microspheres aimed to reduce irritation by releasing the drug in a controlled manner. Microspheres are porous beads, with pore sizes ranging from 10-25 µm in diameter. The tretinoin penetrates the bead pores and, after application, is released gradually into the skin. The penetration properties of the microspheres depend on the size of the particles. Particles larger than 10 µm have been shown to remain on the skin surface.8 It has been shown that 0.1% tretinoin microsphere gel is less irritating than is 0.1% tretinoin cream.9 A disadvantage of 0.1% tretinoin microsphere gel is its rough or "gritty' texture when spread onto the skin, due to the nature of the microsponges and to the fact that some patients