Cutaneous Pharmacokinetics of Topically Applied Novel Dermatological Formulations.

Novel formulations are developed for dermatological applications to address a wide range of patient needs and therapeutic challenges. By pushing the limits of pharmaceutical technology, these formulations strive to provide safer, more effective, and patient-friendly solutions for dermatological concerns, ultimately improving the overall quality of dermatological care. The article explores the different types of novel dermatological formulations, including nanocarriers, transdermal patches, microsponges, and microneedles, and the techniques involved in the cutaneous pharmacokinetics of these innovative formulations. Furthermore, the significance of knowing cutaneous pharmacokinetics and the difficulties faced during pharmacokinetic assessment have been emphasized. The article examines all the methods employed for the pharmacokinetic evaluation of novel dermatological formulations. In addition to a concise overview of earlier techniques, discussions on novel methodologies, including tape stripping, in vitro permeation testing, cutaneous microdialysis, confocal Raman microscopy, and matrix-assisted laser desorption/ionization mass spectrometry have been conducted. Emerging technologies like the use of microfluidic devices for skin absorption studies and computational models for predicting drug pharmacokinetics have also been discussed. This article serves as a valuable resource for researchers, scientists, and pharmaceutical professionals determined to enhance the development and understanding of novel dermatological drug products and the complex dynamics of cutaneous pharmacokinetics.

Novel Approach for the Bioequivalence Assessment of Topical Cream Formulations: Model-Based Analysis of Tape Stripping Data Correctly Concludes BE and BIE.

PURPOSE: The purpose of this study was (a) to suggest a novel dermatopharmacokinetic (DPK) approach from which pharmacokinetic parameters relevant to the bioequivalence (BE) assessment of a topical formulation can be deduced while circumventing the need for numerous measurements and assumptions, and (b) to investigate whether this approach enables the correct conclusion of BE and bioinequivalence (BIE). METHODS: Bioequivalent and bioinequivalent formulations of acyclovir were compared versus a reference product (Zovirax®). Tape Stripping was conducted at only one dose duration during the uptake phase to generate drug content in stratum corneum versus time profiles, each time point corresponding to one stripped layer. Nonlinear mixed effect modeling (ADAPT5®) (MLEM algorithm) was used to fit the DPK data and to estimate the rate (Kin) and extent (FS) of drug absorption/input into the skin. Results were evaluated using the average BE approach. RESULTS: Estimated exposure metrics were within the usual BE limits for the bioequivalent formulation (FS: 102.4 [90%CI: 97.5-107.7]; Kin: 94.2 [90%CI: 83.7-106.0]), but outside those limits for the bioinequivalent formulation (FS: 43.4 [90%CI: 27.9-67.6]; Kin: 54.5 [90%CI: 36.6-81.1]). CONCLUSIONS: The proposed novel DPK approach was shown to be successful, robust and applicable to assess BE and BIE correctly between topical formulations.

Caffeic Acid in Dermatological Formulations: In Vitro Release Profile and Skin Absorption.

AIM AND OBJECTIVE: Caffeic acid (CA) is a cinnamic acid derivative, found in many vegetable products, with powerful antioxidant activity, the ability to increase collagen production and capacity to prevent premature aging of the skin. The classic emulsions of CA are widely used by the consumer to provide a pleasant, refreshing sensorial experience; however, preparations developed in the form of dry film are presented as a technological alternative due to its facile and safe transportation. The aim of this study was to evaluate the release, permeation, and retention of CA in a film and emulsion through in vitro experiments. MATERIAL AND METHODS: The release evaluation of CA from the emulsion and the film was performed using modified Franz diffusion cells, with an area of 1.77 cm², using Microette equipment (Hanson Research) with a cellulose membrane. The evaluation of the permeation of CA from the formulations was conducted using a similar technique of release, except that a biological membrane was used. RESULTS: High release of active compound and reduced permeation was observed, indicating that CA was able to be retained in the epidermis/dermis, where it should have the desired action. The concentration of caffeic acid in the skin was higher for the film formulation than for the emulsion. This demonstrates a greater efficiency of this type of innovative release system, besides its facile and safe transportation. CONCLUSION: The formulations tested in this paper can release caffeic acid with a Higuchi kinetic profile, in which release of active ingredient occurs by a diffusion process. The film formulations exhibited a lower permeation rate and higher retention in the skin, which is essential for a cosmetic product. The concentration of CA in the skin was also higher for the film formulation when compared to the emulsion. This demonstrates a greater efficiency of this type of innovative release system, in addition to its easy and safe transportation. Therefore, it is possible to suggest CA as a promising substance for dermal use due to its antioxidant, anti-inflammatory, antimicrobial, and collagen production stimulating activity.

Honey in dermatology and skin care: a review.

Honey is a bee-derived, supersaturated solution composed mainly of fructose and glucose, and containing proteins and amino acids, vitamins, enzymes, minerals, and other minor components. Historical records of honey skin uses date back to the earliest civilizations, showing that honey has been frequently used as a binder or vehicle, but also for its therapeutic virtues. Antimicrobial properties are pivotal in dermatological applications, owing to enzymatic H2 O2 release or the presence of active components, like methylglyoxal in manuka, while medical-grade honey is also available. Honey is particularly suitable as a dressing for wounds and burns and has also been included in treatments against pityriasis, tinea, seborrhea, dandruff, diaper dermatitis, psoriasis, hemorrhoids, and anal fissure. In cosmetic formulations, it exerts emollient, humectant, soothing, and hair conditioning effects, keeps the skin juvenile and retards wrinkle formation, regulates pH and prevents pathogen infections. Honey-based cosmetic products include lip ointments, cleansing milks, hydrating creams, after sun, tonic lotions, shampoos, and conditioners. The used amounts range between 1 and 10%, but concentrations up to 70% can be reached by mixing with oils, gel, and emulsifiers, or polymer entrapment. Intermediate-moisture, dried, and chemically modified honeys are also used. Mechanisms of action on skin cells are deeply conditioned by the botanical sources and include antioxidant activity, the induction of cytokines and matrix metalloproteinase expression, as well as epithelial-mesenchymal transition in wounded epidermis. Future achievements, throwing light on honey chemistry and pharmacological traits, will open the way to new therapeutic approaches and add considerable market value to the product.

Basic considerations in the dermatokinetics of topical formulations

Assessing the bioavailability of drug molecules at the site of action provides better insight into the efficiency of a dosage form. However, determining drug concentration in the skin layers following topical application of dermatological formulations is a great challenge. The protocols followed in oral formulations could not be applied for topical dosage forms. The regulatory agencies are considering several possible approaches such as tape stripping, microdialysis etc. On the other hand, the skin bioavailability assessment of xenobiotics is equally important for topical formulations in order to evaluate the toxicity. It is always possible that drug molecules applied on the skin surface may transport thorough the skin and reaches systemic circulation. Thus the real time measurement of molecules in the skin layer has become obligatory. In the last two decades, quite a few investigations have been carried out to assess the skin bioavailability and toxicity of topical/dermatological products. This review provides current understanding on the basics of dermatokinetics, drug depot formation, skin metabolism and clearance of drug molecules from the skin layers following application of topical formulations.

A avaliação da biodisponibilidade de moléculas de fármacos no sítio de ação oferece melhor compreensão sobre a eficiência da forma de dosagem. Entretanto, a determinação da concentração de fármaco nas camadas da pele em seguida à aplicação tópica de formulações dermatológicas é um grande desafio. Os protocolos seguidos para as formulações orais não podem ser aplicados para as formulações tópicas. As agências regulatórias consideram várias abordagens possíveis, tape stripping, microdiálise etc. Por outro lado, a avaliação da biodisponibilidade de xenobióticos na pele é igualmente importante para as formulações tópicas para se avaliar a toxicidade. É sempre possível que as moléculas de fármaco aplicadas na superfície da pele sejam transportadas através da pele e alcancem a circulação sistêmica. Assim, a medida em tempo real de moléculas na camada da pele tem se tornado obrigatória. Nas últimas duas décadas, realizaram-se poucas pesquisas para avaliar a biodisponibilidade da pele e a toxicidade de produtos tópicos/dermatológicos. Esta revisão fornece a compreensão atual com base na dermatocinética, formação de fármaco de depósito, metabolismo da pele e o clearance das moléculas de fármaco das camadas da pele em seguida à aplicação de formulações tópicas.