Topical metronidazole is a widely used first line treatment for erythemotelangiectatic and inflammatory rosacea. Commonly, a moisturizer is also used to restore the skin barrier and reduce inflammation. The purpose of this study is to assess the whether the common practice of applying moisturizer prior to topical metronidazole affects this medication's stratum corneum penetrance in rosacea patients. Participants will have one research office visit that will consist of having a randomly assigned combination of metronidazole and one of four moisturizers applied to their face, followed by non-invasive tape stripping of skin at the 1 hour and 4 hour time points. These tape strip samples will be analyzed with liquid chromatography mass spectrometry (LC-MS) for assessment of metronidazole penetrance in the stratum corneum in the presence of moisturizers. The target population will be rosacea patients in the age range of 18-60 years of age. This study has minimal risks/safety issues as topical metronidazole is an already FDA approved medication with an indication for rosacea and all investigated moisturizers are over-the-counter formulations commonly used within the rosacea patient population. Tape stripping will remove 5 levels of superficial stratum corneum, and will not result in bleeding, scarring, or other prolonged cosmetic disfigurement. Small, transient bruising may result from tape strip collection. The collected samples will have no to minimal biohazard risk, as the collected specimen for analysis will only contain skin scale; samples will be extracted with organic solvents and decontaminated with a 0.2 micron nylon filter prior to analysis on the LC-MS instrumentation.

Rosacea is a debilitating spectrum of disease causing both socially embarrassing erythema and disfiguring rhinophyma. Treatment is challenging and life-long, often requiring clinicians to trial multiple medications, such as azelaic acid, metronidazole, or ivermectin to achieve disease control. The skin of rosacea patients inherently has impaired skin barrier function, resulting in inflammation and hypersensitivity to most therapeutics. Thus, many clinicians encourage patients to augment their topical medications with personal moisturizers to optimize the skin barrier. However, there is limited data to support that moisturizers do not affect drug epidermal penetrance and efficacy. To the investigator's knowledge, only a single trial assessing the effect of moisturizers on skin penetrance of azelaic acid has been published in the English literature. In the era of evidence-based medicine, it is critical to provide either the scientific data to support or to refute this medical dogma. The investigator's proposal addresses this gap in the basic science literature and will provide data to evaluate a long and widely-held dermatologist recommendation for the treatment of rosacea. The investigators anticipate that there may be preferred combinations of medication and moisturizers based upon the matched lipophilicities and other chemical properties of the occlusive agent and therapeutic drug. Identification of such combinations may lead to improved outcomes for those struggling with treatment-resistant rosacea and lead to additional pharmaceutical advances in the treatment of rosacea.

Drug formulation is critical to the successful treatment of dermatologic disease. An active ingredient must diffuse through the stratum corneum (SC) to reach the dermis to achieve its therapeutic effect. In addition to the intrinsic chemical properties of the active compound dictating the kinetics of the diffusion process, chemists tweak a topical formulation's vehicle, emulsifiers, and polymers to enhance drug SC penetrance and overcome the skin's evolutionary role as a barrier to the outside world. The combination of drug with additional topical moisturizers inherently changes the chemical environment that the active drug must diffuse through to reach the dermis. Moisturizers and other topical cosmetics are well established to affect dermal drug and toxin absorption. For example, moisturizers have been demonstrated to enhance dermal penetrance of herbicide 2,4-dichlorophenoxacetic acid in murine models. Similarly, occlusive moisturizers are often applied over steroids to enhance their anti-inflammatory efficacy, presumably through improved epidermal penetration. Increased penetrance is a case-by-case scenario, however, and considerable attention is dedicated to topical formulation to appropriately modulate therapeutic drug penetrance of the SC during the drug design process.

To the investigator's knowledge, the formulation and timing of moisturizer application on drug efficacy in rosacea is understudied. An extensive literature review revealed only a single study addressing this important question for the special case of azelaic acid with an in vitro Franz cell diffusion assay using donated trunk skin biopsies. In this study, a 14C radiolabeled 15% azelaic acid gel was applied to epidermis before or after the application of Dove Lotion, CeraVe Moisturizer Lotion, and Cetaphil Moisturizing Lotion. The penetrance of azelaic acid into the SC was then assessed up to 48 hours post-application using liquid scintillation spectrometry. Azelaic acid SC penetration was not statistically different between the moisturizers or timing of application, although trends towards decreased penetration was noted in 1 of 3 studied moisturizers. There are several limitations to this study. First, azelaic acid occupies a unique chemical space among rosacea therapies. Azelaic acid's lipophilicity (LogP), an important chemical property affecting epidermal drug penetrance, is 1.6 compared with 5.83, 0.0, -0.3 and -0.7 for ivermectin, metronidazole, monocycline, and doxycycline, respectively, suggesting that azelaic acid is between 1.4e2 times more lipophilic to 1.7e4 times less lipophilic than other therapies. Thus, azelaic acid is a poor standard with which to assess moisturizers' impact on SC drug penetrance. Second, truncal skin was used to assess azelaic acid SC penetrance. Consequently, the study's clinical relevance is limited as rosacea exclusively affects the face, where the skin is much thinner and transdermal absorption occurs more readily. Finally, although a tritium diffusion control was implemented to select skin samples with relatively intact barrier function, a Franz cell diffusion assay inherently utilizes dead, enzymatically inactive skin. Thus, the results of a Franz cell assay is not necessarily clinically relevant or reflective of physiologically active skin on patients. Further work is necessary to determine whether moisturizers affects drug SC penetrance in rosacea patients.

In prior work, the investigators made method advances that overcome many of the limitations of the Franz cell assay as it relates to clinical relevance. Specifically, the investigators have established a track record of assessing drug penetrance of topically delivered medications, e.g. tazarotene, allantoin, ketoconazole, and betamethasone dipropionate, in the SC using minimally invasive D-squame tape stripes of human subjects in combination with liquid chromatography mass spectrometry (LC-MS). In these studies, the investigators are able to assess drug penetrance with physiologically relevant skin and on skin affected by the disease of interest. Therefore, the methods the investigators propose for assessing metronidazole SC penetrance in the presence of moisturizers is now established as an efficient and reliable method for quantitating drug in the SC in a minimally invasive and clinically relevant context.

Inclusion Criteria:

1. Healthy, non-pregnant individual 18+ years of age;
2. Subjects willing to allow a series of tape pieces to be pressed and removed from their faces over an 4 hour period;
3. Subjects can remain calm and quiet at the research facility for 6 hours;
4. Subjects in general good health as determined from a medical history;
5. Subjects must read and sign the informed consent form after the nature of the study has been fully explained.

Exclusion Criteria:

1. Subjects with known allergies or sensitivities to ingredients contained in the test products;
2. Subjects with an allergy to latex or adhesives;
3. Subjects with excessive visible sun damage on the face, such that the dermatologist investigator considers the subject unsuitable for study entry;
4. Subjects with skin growths or other issues on the face that could interfere with the tape sampling;
5. Subjects who are currently participating in any other clinical study (i.e., dermal patch, use tests, investigational drug or devices, etc.);
6. Subjects viewed by the investigator as not being able to complete the study;
7. Subjects unwilling to refrain from using any type of lotion, medication, or other topical product to the face for a set amount of time prior to the study.