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
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.
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
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
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