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