Topical dermatological products topically applied products intended for local action may have unintended systemic absorption variety of dosage forms. It covers the entire body and has a surface area of approximately 2 m 2 with thickness ranging from 0. This article covers the principles of topical treatments, vehicles used and a number of commonly used topical agents, including corticosteroids. Improved bioequivalence assessment of topical dermatological. Pharmacokinetic approach the application of pharmacokinetic approach in the be assessment of topical dermatological products is limited. Roberts, percutaneous absorption of salicylates from some commercially available topical products containing methyl salicylate or salicylate salts in rats, journal of pharmacy and pharmacology, 47, 11, 891896, 2011. However, such data is not readily available or even measured for most products. Topical be has been a topic of much discussion among researchers, industry, and agency table 1. Seven comprehensive sections examine topics including in vitro drug release, topical drugs products, clinical studies, and guidelines and workshop reports, among others.
Federal register draft guidance for industry on topical. Providing state of theart strategies for the control of irritation and infection, topical absorption of dermatological products is an indepth source for dermatologists, pharmacists, pharmacologists, cosmetic scientists, biochemists, toxicologists, public health officials, manufacturers of cosmetics and toiletries, and upperlevel. Oct 22, 2008 a dermatopharmacokinetic dpk approach, in which drug levels in the stratum corneum sc are measured as a function of time postapplication and postremoval of the product using tapestrip sampling in vivo in humans, has been considered for the comparative assessment of topical bioavailability. Blood flow as a technology in percutaneous absorption. Several studies have found an association of nonhodgkins lymphoma with the use of hair dyes. Download citation on jan 31, 2003, ulrich schafer and others published topical absorption of dermatological products find, read and cite all the research. Overthecounter topical musculoskeletal pain relievers used. In general, topical dermatological drug products are not intended for systemic absorption.
A topically applied drug is any medication that is applied to the bodys surface e. Pharmacokinetics related to topical applications of drugs describes the time dependent drug. Drug development in dermatology important considerations. Basic considerations in the dermatokinetics of topical formulations 425 temperature, formulation compositions etc and are discussed briefly. Pdf dermatological drugs, topical agents, and cosmetics. A dermatopharmacokinetic dpk approach, in which drug levels in the stratum corneum sc are measured as a function of time postapplication and postremoval of the product using tapestrip sampling in vivo in humans, has been considered for the comparative assessment of topical bioavailability. General categories include ophthalmic and otic preparations, mouth, throat, and anorectal preparations, spermicides and vaginal preparations, irrigating solutions. Many excipients used in topical drug products have dual or multiple functionalities. Oct 09, 2012 topical dermatologic products, which can be administered easily and are convenient in terms of portability, are used in treating a variety of disorders. Banga, professor and chair of the department of pharmaceutical sciences, mercer university the use of topical route for drug delivery relies on the formulation of effective dermatological products, which maximize drug availability at the. To minimize absorption, rinse hair thoroughly after use and remove all traces. Topical dermatological agents are applied directly on the skin to treat skin conditions. Principles of topical dermatologic therapy dermatologic. Pdf guidance for industry topical dermatological drug.
Topical absorption of dermatological products robert l. There are only a limited number of acceptable methods for determining be between the generic topical dermatological products and reference list products. Topical dermatologic products, which can be administered easily and are convenient in terms of portability, are used in treating a variety of disorders. Pdf challenges in evaluating bioequivalence of topical dermatological drug products.
The assessment of the cutaneous microcirculation by laser doppler and photoplethysmographic techniques 195 ethel tur 15. While topical prod ucts to treat dermatological ailments have been in existence from the earliest times, transdermal products, where skin is used as an alternative. Traditionally, topical therapy carrier vehicles were developed empirically by combining favorite and known ingredients affecting the percutaneous absorption of the drugactive ingredient. However, the most effective topical treatment for dermatophyte infections is a cream containing an imidazole such as miconazole, which is effective for longestablished lesions but is more expensive than compound benzoic acid ointment. In contrast to orally administered products, most topical dermatological products are meant to be locally active, which provide limited systemic absorption, thus precluding the application of common procedures for be determination of orally administered products i. The protocols followed in oral formulations could not be applied for topical dosage forms. Maibach university of california school of medicine san francisco, california marcel dekker, inc. Indications for use and common adverse effects of these topical agents are outlined. There was little consideration of cosmetic acceptability and limited knowledge of the skin penetration permeation of the drug at the target site. The pharmacokinetic approach has accelerated the development of highquality generic medicines with extraordinary cost savings, transforming the pharmaceutical industry and healthcare system in the usa. Bioequivalence of topical dermatological products springerlink. The quality of a pharmaceutical dosage form is the foremost criterion during the development of a product. Pharmacokinetic assessment of topical drug products has previously been plagued by bioanalytical assay limitations and the lack of a standardized study design. The human skin is a preferred route for the topical delivery of therapeutic molecules targeting local dermatological disorders.
Containing 350 illustrations, tables, and equations and covering aapsfda guidelines for the experimentation and analysis of in vivo and in vitro percutaneous absorption, this reference provides comprehensive coverage of the development, preparation, and application of topical and transdermal therapeutic systems. Oct 25, 2014 in general, topical dermatological drug products are not intended for systemic absorption. Topical therapies constitute an important aspect of dermatological treatments. Topical absorption of dermatological products edited by robert l. To minimize absorption, rinse hair thoroughly after use and remove all traces from skin including nails adverse effects. Principles and criteria in the development and optimization of topical. Topical drug bioavailability, bioequivalence, and penetration. Dermatological and transdermal formulations 1st edition. Fda recognized the need to find more sensitive and efficient surrogate approaches to demonstrate be for topical dermatological products.
Always consult your healthcare provider to ensure the. Workshop report principles and criteria in the development. Pharmacokineticsbased approaches for bioequivalence. Topical drugs, the mainstay of treatment in dermatology, are applied in the hope and expectation that any percutaneous absorption will be minimal and that systemic side effects will not occur. Pharmacokinetics and topical applications of drugs. Since the mid1990s the us food and drug administration has developed and implemented a pharmacokinetic maximal usage trial must design to help address these issues. Topical absorption of dermatological products researchgate. The information and comments from the public and advisory committees raised substantial doubt regarding.
Maximal use pharmacokinetic trial design for topical. Quality by design qbd for topical dermatologic products. Approaches for bioequivalence assessment of topical. While this is true for systemically absorbed drug products, the availability of generic versions of topical dermatological products remains constrained due to. Topical drug products exert their action at or on the surface of the skin stratum. Topical products include a broad array of preparations that are designed to deliver drugs externally to prevent or treat disease andor to alleviate symptomatology. With contributions from worldrenowned experts in the field, topical absorption of dermatological products summarizes. Bioequivalence be assessment of topical dermatological products is a long standing challenge. This article covers the principles of topical treatments, the vehicles used and a number of commonly used topical agents, including corticosteroids.
Its application todate has been limited by contradictory results and concerns that variability in. Previous studies have suggested an association between the use of hair dyes and some cancers. Often, even when a topical dermatological drug product is. The skin is involved in many functions, such as providing a protective barrier from the external environment e. Drug products topically administered via the skin fall into two general categories. They can be applied to any of the diverse external surfaces of 17. Flynn gl 1990 topical drug absorption and topical pharmaceutical systems. However, in some special cases where there is significant systemic absorption pharmacokinetic studies can be used to assess the be of topical products. Therefore, the utilization of in vivo pharmacokinetic pk studies, an established approach for be assessment of solid oral dosage forms, is often not appropriate for topical dosage forms. They may deliver medicines to prevent or treat skin disorders or have inert creams and ointments for routine skin care to maintain the skin, which may be susceptible to skin disorders. Comments and suggestions regarding this draft document should be submitted within 60 days of publication of the federal register notice announcing the availability of the draft guidance. Submit comments to dockets management branch hfa305, food and drug administration, 12420 parklawn dr.
Bioavailability of topical dosage forms suthakaran c. Feb 20, 2002 containing 350 illustrations, tables, and equations and covering aapsfda guidelines for the experimentation and analysis of in vivo and in vitro percutaneous absorption, this reference provides comprehensive coverage of the development, preparation, and application of topical and transdermal therapeutic systems. Advance in bioequivalence assessment of topical dermatological. Topical absorption of dermatological products basic and. To design a topical vehicle that provided the optimal balance of betamethasone dipropionate penetration and retention in the skin, with minimal systemic absorption. Formulation drug product quality attributes in dermal physiologicallybased pharmacokinetic models for topical dermatological drug products and transdermal delivery systems rfafd18019. Systemic absorption of topical corticosteroids may occur and cause adrenal suppression.
Many drug types fall under the umbrella of topical drugs, including lotions, creams, ointments. In contrast to orally administered products, most topical dermatological products are meant to be locally active, which provide limited systemic absorption, thus precluding the application of common procedures for be determination of orally administered. Topical skin medications deliver effective targeted therapies that are easy to apply and offer reduced risks of systemic side effects. Indications for use and common side effects of these topical agents are mentioned. Bioavailability and bioequivalence of dermatological. Basic considerations in the dermatokinetics of topical. The assessment of the bioequivalence be of topical dermatological formulations is a long standing challenge. Overthecounter topical musculoskeletal pain relievers. Overcoming barriers and improving patient access to topical dermatological drugs. Dermatological drugs topical antifungal drugs ringworm benzoic acid and methylrosanilinium chloride gentian violet. Demonstrating dermatological bioequivalence beyond the in vivo clinical endpoint bioequivalence study john r peters, md. Topical absorption of dermatological products taylor. Dermatological drugsproducts and cosmetics with regard.
Online topical absorption of dermatological products. Providing stateoftheart strategies for the control of irritation and infection, topical absorption of dermatological products is an indepth source for dermatologists, pharmacists, pharmacologists, cosmetic scientists, biochemists, toxicologists, public health officials, manufacturers of cosmetics and toiletries, and upperlevel. Topical preparations exist in many forms, such as ointments, gels, creams, lotions, solutions, suspensions, foams, and shampoos. The book also describes how targeted transdermal drug delivery and more sophisticated mathematical modelling can aid in understanding the bioavailability of transdermal drugs. Effect of single versus multiple dosing in percutaneous absorption 185 ronald c. Trends in the topical delivery of dermatology medications. Its application todate has been limited by contradictory.
Extensive and generalized infections of the skin, nails and scalp should be. To establish the be of most topical dermatological products, barring dermatological corticosteroids, the only. Morra et al 10 studied 12 volunteers 6 women, 6 men who applied either 5 g of methyl salicylate ointment 12. Topical dermatological products act locally, and local tissue concentrations at the site of action is a critical component in determine bioequivalence for such products. Factors affecting surface drug absorption many factors affect how the application of a particular drug will be absorbed by the skin surface. Topical solutions topical solutions are liquid preparations, that usually are aqueous but often contain other solvents such as alcohol and polyols that contain one or more dissolved chemical substances intended for topical application to the skin, or, as in the case of lidocaine oral topical solution usp, to the oral mucosal surface. However, determination of topical be for locally acting drugs in skin is more complicated than solid dosage forms. Online topical absorption of dermatological products basic. Topical dermatological agents include local anesthetics, cleansing agents, antiinflammatory agents, antiinfective agents, emollients, astringents, agents to treat acne, antivirals, antifungals, agents for psoriasis such as topical corticosteroids, and so on. Transdermal and topical products are increas ing in importance and their use in therapy is becoming more widespread.
Historically, there were limited options for alternate approaches to clinical endpoint be studies. Concept paper on guideline on quality and equivalence of. Quality by design qbd for topical dermatologic products opinions expressed in this presentation are those of the speaker and do not necessarily reflect the views or policies of the fda andre s. Topical corticosteroids 16 bases and vehicles objectives following completion of this material the student should. This chapter discusses the adverse effects of dermatological drugs, topical agents, and cosmetics such as hair dyes, henna, pimecrolimus, and minoxidil. Occlusive dressings applied over topical corticosteroids to increase absorption are sometimes used to treat psoriasis, atopic dermatitis, skin lesions resulting from systemic lupus erythematosus, and chronic hand dermatitis, among other conditions. D director division of chemistry i fdacderoffice of generic drugs andre. Nih funding opportunities and notices in the nih guide for grants and contracts. General categories include ophthalmic and otic preparations, mouth, throat, and anorectal preparations, spermicides and vaginal preparations, irrigating solutions, antiseptics and germicides, and dermatological products. Bioequivalence of topical dermatological drug products. Table 1 regulatory information pertaining to be of topical dermatological drug products1 year comments. Bioequivalence of topical dermatological drug products kasha pc and banga ak department of pharmaceutical sciences, college of pharmacy and health sciences, 3001 mercer university drive, mercer university, atlanta, ga 30341 to whom correspondence should be addressed. Quality by design approaches for topical dermatological dosage forms arunprasad sivaraman, ajay k banga department of pharmaceutical sciences, college of pharmacy, mercer university, atlanta, ga, usa abstract. The systemic absorption of otc formulations also has been studied.
Demonstrating dermatological bioequivalence beyond the in vivo clinical endpoint bioequivalence study. Bioequivalence assessment of locally acting topical dosage forms is challenging. All comments should be identified with the docket number listed in the. Indications for use and common adverse effects of these topical agents are mentioned.
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