P136
Pharmacology of salicylic acid (SA) in acne vulgaris
Otto Mills, PhD, Robert Wood Johnson Medical School, New Brunswick, NJ,
United States; Donald Adler, DO, private practice, Doylestown, PA, United States;
Robert Verdicchio, PhD, Verdi Enterprise, Succasunna, NJ
The role of SA is acne treatment is dependent upon several pharmacological actions
and its physiochemical properties. The SA molecule is a beta hydroxy acid and has a
3 PKa making it a weak organic acid although the acidity is below the acid mantle of
skin which is about 5.0. Many drugs designed for pharmaceutical application to skin
are weak acids or bases; however, of more importance is the PKa which is an
indication of both activity and disassociation of the proton from the carbonyl moiety.
The molecular size together with lipid solubility are important physiochemical
properties. The former promotes rapid penetration of SA into the follicle while lipid
solubility induces a peptizing effect on sebum and cellular material making up the
microcomodones. Based on a study of comedolytic activity in acne, it was stated that
SA seemed to ‘‘detach horny cells from each other by weakening the intracellular
cement. As a result, the comedo tends to undergo disorganization. SA penetrated
skin readily and increases turnover which also favors exfoliation of the comedo.’’
Another study used high pressure liquid chromatography (HPLC) to measure SA
penetration into harvested microcomodones and related this to clinical activity of
tested formulations. This presentation defines and details pharmacological activities
of SA as it pertains to the treatment of acne and also discusses combination therapy
with benzoyl peroxide.
100% is supported by JSJ Pharmaceuticals.
P137
A comparison of patterns of deposition of two formulations of benzoyl
peroxide on the skin and in the follicular ostia as visualized by scanning
electron microscopy
Mary C. Spellman, MD, private practice, San Francisco, CA, United States; Jose
Ramirez, PhD, JR Chemical, Milford, CT, United States
The overwhelming majority of topical benzoyl peroxide (BPO) formulations
are emulsions, comprised of large, highly insoluble macro-particles. The BPO is
entrapped in the vehicle, creating an obstacle to effective delivery to the infected
and inflamed follicle that is responsible for the clinical manifestations of acne
vulgaris. Commercially successful BPO formulations deliver approximately 0.03% to
1.0% of the available BPO to the follicle. A novel and proprietary BPO formulation is
expected to deliver nearly the full concentration of the BPO, effecting far greater
antimicrobial potency, and, as a consequence, greater reduction in acne lesion
counts. To evaluate the patterns of deposition of a commercially available generic
5% BPO on the skin and into the follicular ostia, and to compare with the novel 5%
BPO formulation, a scanning electron microscopy evaluation was performed. Thirty
minutes following gentle cleansing of the face, a replica of the skin surface was
created with a silicone elastomer. After recleansing, the same areas on the right
and left face were treated with either a single application of the control or the
proprietary BPO formulation, and 30 minutes thereafter, a silicone elastomer replica
was created. Scanning electron microscopy was performed on the 4 skin replicas
after the received negative image was converted to a positive image; the examiner
was blinded with regard to type of treatments or anticipated effects. Prior to
application of the BPO formulations, neither side demonstrated particulate matter
on the surface of the skin or in the follicles. The superficial squamous cells were
intact and regular in appearance. Following application of the control product, a
significant volume of residual material was clearly visible on the surface of intact
squamous cells; there was no evidence of similar material in the follicles.
Importantly, at the site of application of the novel BPO, there was no visible residue
on the skin surface, but there was well-defined globular material evident in the
follicular ostia. The patterns of deposition of BPO on the skin of a healthy adult
volunteer indicate that BPO from the novel formulation can successfully access the
follicular ostia and penetrate the follicle to the primary locale of the pathogenesis of
acne. Although this data is limited to that from a single exposure, clinical studies of
antimicrobial efficacy support the hypothesis that this formulation reaches the
follicle.
This study was funded by OMP, Inc.
AB22 J AM ACAD DERMATOL
P138
A sebum dissolving microgel complex enhances targeted delivery in
different acne treatment formulations
Jeff Wu, PhD, Johnson & Johnson Consumer & Personal Products Worldwide,
Skillman, NJ, United States; Theresa Chen, PhD, Neutrogena, Los Angeles, CA,
United States; Jeannette Chantalat, MS, Johnson & Johnson Consumer & Personal
Products Worldwide, Skillman, NJ, United States; Jue-Chen Liu, PhD, Johnson &
Johnson Consumer & Personal Products Worldwide, Skillman, NJ, United States
The presence of the excessive sebum produced by sebaceous glands and the
compacted keratinous material plays an important role leading to follicular
obstruction and formation of micro-comedos, which is the precursor to acne. It is
therefore essential to break through the sebum barrier to effectively target delivery
of acne medication into the pilosebaceous follicle. Through screening a wide range
of cosmetic ingredients, such as solvents, emollients, essential oils, and plant
extracts, for their sebum solublities, a novel microgel complex has been developed
and shown to enhance sebum solubilization and the delivery of acne medication (eg,
salicylic acid) deep into the skin. In clinical studies with subjects of mild to moderate
acne, both leave-on and rinse-off formulations (eg, spot treatment gel and foaming
cleanser) containing the microgel complex with 0.5% to 2% salicylic acid have
consistently demonstrated significant anti-acne efficacy. We present the new study
results that demonstrate the superior sebum dissolving capability in both in vitro
and ex vivo sebum models for the salicylic acid microgel complex in several product
forms. In addition, these results are correlated to the in vivo follicular delivery of
salicylic acid evaluated by follicular biopsy. The novel acne treatment microgel
technology has the follicular delivery enhancement advantage and the broad
applicability into different product forms for effective acne treatment.
Fully supported by Johnson & Johnson Consumer & Personal Products Worldwide.
P139
The hormonal treatment of acne: A practical guide
Elizabeth White, Wake Forest University Health Sciences, Winston Salem, NC,
United States; Steven Feldman, MD, PhD, Wake Forest University Health
Sciences, Winston Salem, NC, United States
Many therapies exist in the arsenal of drugs available to dermatologists in the
treatment of acne vulgaris. Among them, hormonal therapy stands out as a unique
and highly efficacious treatment modality. Although there may be some hesitancy on
the part of dermatologists to prescribe hormonal therapies, they can indeed be used
safely and appropriately in well-selected female patients. Herein, current issues
regarding the hormonal treatment of acne are presented, and a practical method for
implementing this therapy is proposed. Specifically, patient and drug selection,
risks, benefits, and monitoring are discussed with emphasis on practicality of use in
the clinical setting.
The Center for Dermatology Research is supported by an educational grant from
Galderma Laboratories, LP.
FEBRUARY 2007