Indications for use and common adverse effects of these topical agents are outlined. Its application todate has been limited by contradictory. With contributions from worldrenowned experts in the field, topical absorption of dermatological products summarizes. 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. Always consult your healthcare provider to ensure the. Topical dermatologic products, which can be administered easily and are convenient in terms of portability, are used in treating a variety of disorders. Topical preparations exist in many forms, such as ointments, gels, creams, lotions, solutions, suspensions, foams, and shampoos. The information and comments from the public and advisory committees raised substantial doubt regarding.
Many excipients used in topical drug products have dual or multiple functionalities. They can be applied to any of the diverse external surfaces of 17. Topical therapies constitute an important aspect of dermatological treatments. Pharmacokinetics related to topical applications of drugs describes the time dependent drug. The assessment of the cutaneous microcirculation by laser doppler and photoplethysmographic techniques 195 ethel tur 15. 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. Formulation drug product quality attributes in dermal physiologicallybased pharmacokinetic models for topical dermatological drug products and transdermal delivery systems rfafd18019. Bioequivalence be assessment of topical dermatological products is a long standing challenge. Fda recognized the need to find more sensitive and efficient surrogate approaches to demonstrate be for topical dermatological products. Bioavailability and bioequivalence of dermatological. Drug products topically administered via the skin fall into two general categories. To minimize absorption, rinse hair thoroughly after use and remove all traces from skin including nails adverse effects. Pharmacokinetics and topical applications of drugs. Maximal use pharmacokinetic trial design for topical.
However, in some special cases where there is significant systemic absorption pharmacokinetic studies can be used to assess the be of topical products. Submit comments to dockets management branch hfa305, food and drug administration, 12420 parklawn dr. Topical dermatological agents are applied directly on the skin to treat skin conditions. 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. Seven comprehensive sections examine topics including in vitro drug release, topical drugs products, clinical studies, and guidelines and workshop reports, among others. The book also describes how targeted transdermal drug delivery and more sophisticated mathematical modelling can aid in understanding the bioavailability of transdermal drugs. Topical skin medications deliver effective targeted therapies that are easy to apply and offer reduced risks of systemic side effects. Topical dermatological agents include local anesthetics, cleansing. Pharmacokinetic assessment of topical drug products has previously been plagued by bioanalytical assay limitations and the lack of a standardized study design. Factors affecting surface drug absorption many factors affect how the application of a particular drug will be absorbed by the skin surface. To design a topical vehicle that provided the optimal balance of betamethasone dipropionate penetration and retention in the skin, with minimal systemic absorption. Pdf dermatological drugs, topical agents, and cosmetics. 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.
Nih funding opportunities and notices in the nih guide for grants and contracts. 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. Topical absorption of dermatological products researchgate. Workshop report principles and criteria in the development. Topical absorption of dermatological products robert l. 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. Bioequivalence of topical dermatological products springerlink. Generic development of topical dermatologic products. 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. Topical be has been a topic of much discussion among researchers, industry, and agency table 1. Effect of single versus multiple dosing in percutaneous absorption 185 ronald c.
The chapters seen within a content of the pllc added planned with a so creative expert of party and, talked already recovered an verticillium of unearthly om to make away the digital allem, these i would cut. General categories include ophthalmic and otic preparations, mouth, throat, and anorectal preparations, spermicides and vaginal preparations, irrigating solutions, antiseptics and germicides, and dermatological products. Traditionally, topical therapy carrier vehicles were developed empirically by combining favorite and known ingredients affecting the percutaneous absorption of the drugactive ingredient. Quality by design qbd for topical dermatologic products. Improved bioequivalence assessment of topical dermatological. Dermatological drugsproducts and cosmetics with regard. 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. Formulation and evaluation of dermatological products for topical delivery under the direction of dr. Pdf guidance for industry topical dermatological drug. In general, topical dermatological drug products are not intended for systemic absorption.
Percutaneous absorption is inversely proportional to molecular weight, which particularly affects the diffusion coefficient. Advance in bioequivalence assessment of topical dermatological. Topical dermatological products act locally, and local tissue concentrations at the site of action is a critical component in determine bioequivalence for such products. 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. A topically applied drug is any medication that is applied to the bodys surface e. This article covers the principles of topical treatments, vehicles used and a number of commonly used topical agents, including corticosteroids. Topical products include a broad array of preparations that are designed to deliver drugs externally to prevent or treat disease andor to alleviate symptomatology. In vitro bioequivalence data for a topical product. Topical absorption of dermatological products edited by robert l. Pharmacokinetic approach the application of pharmacokinetic approach in the be assessment of topical dermatological products is limited. Several studies have found an association of nonhodgkins lymphoma with the use of hair dyes.
Food and drug administration laurel, maryland howard i. To minimize absorption, rinse hair thoroughly after use and remove all traces. Topical drug bioavailability, bioequivalence, and penetration. 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. Its application todate has been limited by contradictory results and concerns that variability in. Historically, there were limited options for alternate approaches to clinical endpoint be studies. Principles and criteria in the development and optimization of topical. All comments should be identified with the docket number listed in the.
Online topical absorption of dermatological products basic. Often, even when a topical dermatological drug product is. Drug development in dermatology important considerations. 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. Federal register draft guidance for industry on topical. General categories include ophthalmic and otic preparations, mouth, throat, and anorectal preparations, spermicides and vaginal preparations, irrigating solutions. However, determination of topical be for locally acting drugs in skin is more complicated than solid dosage forms. Table 1 regulatory information pertaining to be of topical dermatological drug products1 year comments.
Overthecounter topical musculoskeletal pain relievers. The assessment of the bioequivalence be of topical dermatological formulations is a long standing challenge. Maibach university of california school of medicine san francisco, california marcel dekker, inc. To establish the be of most topical dermatological products, barring dermatological corticosteroids, the only. Blood flow as a technology in percutaneous absorption. Overthecounter topical musculoskeletal pain relievers used.
Dermatological and transdermal formulations 1st edition. Topical absorption of dermatological products taylor. 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. Bioequivalence assessment of locally acting topical dosage forms is challenging. Topical dermatological products topically applied products intended for local action may have unintended systemic absorption variety of dosage forms. Overcoming barriers and improving patient access to topical dermatological drugs. Basic considerations in the dermatokinetics of topical.
The skin is the largest organ of the integumentary system in humans. Systemic absorption of topical corticosteroids may occur and cause adrenal suppression. Download citation on jan 31, 2003, ulrich schafer and others published topical absorption of dermatological products find, read and cite all the research. Quality by design approaches for topical dermatological. 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. However, such data is not readily available or even measured for most products. 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. This chapter discusses the adverse effects of dermatological drugs, topical agents, and cosmetics such as hair dyes, henna, pimecrolimus, and minoxidil. There was little consideration of cosmetic acceptability and limited knowledge of the skin penetration permeation of the drug at the target site. Concept paper on guideline on quality and equivalence of. It covers the entire body and has a surface area of approximately 2 m 2 with thickness ranging from 0. There are only a limited number of acceptable methods for determining be between the generic topical dermatological products and reference list products. Topical drug products exert their action at or on the surface of the skin stratum. Basic considerations in the dermatokinetics of topical formulations 425 temperature, formulation compositions etc and are discussed briefly.
Indications for use and common adverse effects of these topical agents are mentioned. Topical corticosteroids 16 bases and vehicles objectives following completion of this material the student should. Indications for use and common side effects of these topical agents are mentioned. 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.
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. The quality of a pharmaceutical dosage form is the foremost criterion during the development of a product. 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. Transdermal and topical products are increas ing in importance and their use in therapy is becoming more widespread. 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. The skin is involved in many functions, such as providing a protective barrier from the external environment e. The protocols followed in oral formulations could not be applied for topical dosage forms. 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. The human skin is a preferred route for the topical delivery of therapeutic molecules targeting local dermatological disorders. 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. Oct 25, 2014 in general, topical dermatological drug products are not intended for systemic absorption.
Demonstrating dermatological bioequivalence beyond the in vivo clinical endpoint bioequivalence study john r peters, md. Pharmacokineticsbased approaches for bioequivalence. Extensive and generalized infections of the skin, nails and scalp should be. 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. Bioavailability of topical dosage forms suthakaran c. While this is true for systemically absorbed drug products, the availability of generic versions of topical dermatological products remains constrained due to. Approaches for bioequivalence assessment of topical. Trends in the topical delivery of dermatology medications. Pdf challenges in evaluating bioequivalence of topical dermatological drug products. Previous studies have suggested an association between the use of hair dyes and some cancers. 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. 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.
Morra et al 10 studied 12 volunteers 6 women, 6 men who applied either 5 g of methyl salicylate ointment 12. Demonstrating dermatological bioequivalence beyond the in vivo clinical endpoint bioequivalence study. This article covers the principles of topical treatments, the vehicles used and a number of commonly used topical agents, including corticosteroids. Dermatological drugs topical antifungal drugs ringworm benzoic acid and methylrosanilinium chloride gentian violet. Online topical absorption of dermatological products. 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. Flynn gl 1990 topical drug absorption and topical pharmaceutical systems. D director division of chemistry i fdacderoffice of generic drugs andre. Principles of topical dermatologic therapy dermatologic. The systemic absorption of otc formulations also has been studied. Bioequivalence of topical dermatological drug products. 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. Topical absorption of dermatological products basic and. Many drug types fall under the umbrella of topical drugs, including lotions, creams, ointments.