INTRODUCTION
Acne and rosacea represent a combined patient population of up to 66 million in the U.S. alone.1,2 These stubborn inflammatory conditions often require repeat or prolonged courses of oral antibiotics that may cause unwanted side effects. This has led to the heavy use of topical antibiotics, often as monotherapy, which in turn contributes to alarmingly high resistance rates reported across the globe.3,4,5,6,7,8,9 P. acnes resistance against erythromycin and clindamycin in Spain has reached 91%,10 and in India it has reached 90%, 98%, and 100% for clindamycin, erythromycin, and azithromycin respectively.11 The resistance rates found in one small U.S. study were 100% for erythromycin and clindamycin, 97% for tetracycline, and 83% for doxycycline.12 Although dermatologists represent about 1% of the U.S. physician population, the specialty is responsible for nearly 5% of all antibiotic prescriptions.13 Over a ten-year period between 2003 and 2013, U.S. dermatologists prescribed antibiotics 8-9 million times annually, accounting for at least 20% of all prescriptions written by dermatologists.14,15,16,17,18 Up to two-thirds of these antibiotic prescriptions were written for the treatment of acne vulgaris.To address the growing resistance problem, the American Academy of Dermatology recently published guidelines for acne treatment, including the use of antimicrobial benzoyl peroxide as a first-line monotherapy or in combination therapy with antibiotics and retinoids. While benzoyl peroxide helps reduce antibiotic resistance,19 barriers to use include failure of the physician to prescribe, poor insurance coverage, and side effects such as stinging, burning, itching, dryness, irritation, and bleaching of fabrics.20 Complex treatment regimens pose additional compliance issues, especially amongst teenagers. The new class of topical minocycline therapies may aid in simplifying regimens and reducing antibiotic resistance, without sacrificing outcomes.Topical Minocycline for AcneMinocycline is a second-generation tetracycline antibiotic and is the most commonly prescribed oral medication for acne vulgaris.21 It has the lowest rate of antibiotic resistance in its class,18,19,21 but is associated with multiple side effects including headache, dizziness, nausea, hyperpigmentation of skin and teeth, autoimmune hepatitis, systemic lupus erythematosus, and ANCA vasculitis.22 Topical minocycline seeks to avoid these side effects via transepidermal delivery and low rates of systemic absorption.Minocycline is a hydrophilic salt that must penetrate the stratum corneum,23 travel against the flow of sebum, and enter the pilosebaceous unit, where inflammation and acne begin. While oral minocycline contains stable, dry end products in salt form, topical minocycline in a semi-solid or liquid form is not stable and will degrade the active pharmaceutical ingredient (API). Lipid-based formulations, on the other hand, do stabilize tetracycline salts but exist in a suspension that may reduce API solubility and bioavailability. Therefore, higher doses of API are required in lipid formulations to maintain a concentration gradient that will drive transepidermal delivery. Hydrophilic gels containing ethanol fully solubilize minocycline and rapidly
