Search

Given the pivotal role played by the microbiome in skin health, it is important to understand how its composition varies with age, sex, and body site and regular use of topical products. Four studies were carried out to determine the effects of long-term (4-week) use of different dexpanthenol-containing topical products on the skin microbiome of a varied population with cosmetically dry skin. The skin microbiome composition was assessed before and after product usage. No significant changes in microbiome richness or diversity were found for the individual test products; however, a meta-analysis of the combined dataset did show changes in microbiome composition as a function of the subject's sex, age, and body site. The work presented here demonstrates how the use of carefully formulated topical products on skin, when used in a way that is representative of real-life usage conditions, can respect the microbial diversity present on skin across a widely varied study population. [ABSTRACT FROM AUTHOR]

The 2023 Generic Drug Science and Research Initiative Public Workshop organized by the U.S. Food and Drug Administration (FDA) discussed the research needs to improve and enhance bioequivalence (BE) approaches for generic drug development. FDA takes such research needs and panel discussions into account to develop its Generic Drug User Fee Amendments III (GDUFA III) Science and Research Initiatives specific to generics. During the five workshop sessions, presentations and panel discussions focused on identifying and addressing scientific gaps and research needs related to nitrosamine impurity issues, BE assessment for oral products, innovative BE approaches for long-acting injectable products, alternative BE approaches for orally inhaled products, and advanced BE methods for topical products. Specifically, this report highlights the discussions on how to improve BE assessment for developing generic drug products based on research priorities for leveraging quantitative methods and modeling, as well as artificial intelligence/machine learning (AI/ML). [ABSTRACT FROM AUTHOR]

Given the pivotal role played by the microbiome in skin health, it is important to understand how its composition varies with age, sex, and body site and regular use of topical products. Four studies were carried out to determine the effects of long-term (4-week) use of different dexpanthenol-containing topical products on the skin microbiome of a varied population with cosmetically dry skin. The skin microbiome composition was assessed before and after product usage. No significant changes in microbiome richness or diversity were found for the individual test products; however, a meta-analysis of the combined dataset did show changes in microbiome composition as a function of the subject’s sex, age, and body site. The work presented here demonstrates how the use of carefully formulated topical products on skin, when used in a way that is representative of real-life usage conditions, can respect the microbial diversity present on skin across a widely varied study population.

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The rheological and viscoelastic properties of hybrid formulations composed of vehicles designed for cutaneous topical application and loaded with ultradeformable liposomes (UDL) were assessed. UDL were selected for their established ability to transport both lipophilic and hydrophilic compounds through the skin, and are applicable in pharmaceuticals and cosmetics. Formulations underwent flow analysis and were fitted to the Herschel–Bulkley model due to their prevalent non-Newtonian behavior in most cases. Linear viscoelastic regions (LVR) were identified, and G′ and G″ moduli were determined via frequency sweep steps, considering the impact of temperature and aging. The formulations exhibited non-Newtonian behavior with pseudoplastic traits in most cases, with UDL incorporation inducing rheological changes. LVR and frequency sweep tests indicated predominantly elastic solid behavior, with G′ higher than G″, at different temperatures and post-production times. Tan δ values also illustrated a predominant solid-like behavior over liquid. This study provides pivotal insights into the rheological and viscoelastic features of topical formulations, emphasizing the crucial role of meticulous vehicle and formulation selection when incorporating UDL or analogous liposomal drug delivery systems. [ABSTRACT FROM AUTHOR]

The use of in vitro human skin permeation tests is of value when addressing the quality and equivalence of topical drug products in Europe and the US. Human skin is the membrane of choice for these studies. The use of human skin as a membrane is hindered by limited access, high variability of results, and limited applicability for drugs with low skin permeability. Reconstructed human epidermis (RhE) models are validated as skin surrogates for safety tests and have been explored for percutaneous absorption testing. Clotrimazole poorly permeates human skin and is widely available for topical treatments. In this study, clotrimazole creams were used to test the ability of RhE to be used as biological membrane for bioequivalence testing, based on the Draft Guideline on Quality and Equivalence of Topical Products (CHMP/QWP/708282/2018) using a discriminative and modified in vitro permeation test (IVPT). To fulfill the validation of a discriminatory method, Canesten® 10 mg/g cream was compared with a test product with the same drug strength, along with two "negative controls" dosed at a 50% and 200% drug strength. Products were compared in finite dose conditions, regarding maximal flux (Jmax) and the total amount of drug permeated (Atotal). The results showed the discriminatory power of the method among the three drug strengths with no interference of the placebo formulation. The study design and validation complied with the requirements established in the guideline for a valid IVPT. This new test system allowed for the equivalence comparison between test and comparator product. Higher permeability of the RhE compared to human skin could be observed. This arose as a strength of the model for this modified IVPT bioequivalence testing, since comparing permeation profiles among products is envisaged instead of drawing absolute conclusions on skin permeation extent. These results may support the acceptance of RhE as biological membranes for modified IVPT in bioequivalence testing of topical products. [ABSTRACT FROM AUTHOR]

Purpose: Following the recent European Medicine Agency (EMA) draft guideline on quality and equivalence of topical products, a modular framework for bioequivalence assessment is proposed, wherein the qualitative, quantitative, microstructure and product performance sameness is demanded to support generic applications. Strict regulatory limits are now imposed, but, the suitability of these limits has been subject of intense debate. In this context, this paper aims to address these issues by characterizing a panel of 8 reference blockbuster semisolid topical products. Methods: For each product, three batches were selected and, whenever possible, batches retrieved from different manufacturing sites were considered. Product microstructure was evaluated in terms of globule size, pH, rheological attributes and, if required, the thermal behaviour was also assessed. Performance was evaluated through in vitro release testing (IVRT). Finally, an integrated multivariate analysis was performed to highlight the features that most contribute for product variability. Results: Marked differences were registered within reference products. Statistical analysis demonstrated that if EMA criteria are applied, none of the same product batches can be considered as equivalent. Rheological parameters as well as IVRT indicators account for the majority of batch-to-batch differences. Conclusions: Semisolid dosage forms exhibit intrinsic variability. This calls for the attention to the need of establishing reasonable equivalence criteria applied to generic drug products. [ABSTRACT FROM AUTHOR]

Inter- and intra-batch variability of the quality attributes contribute to the uncertainty for demonstrating equivalent microstructure of post-approval changes and generic/hybrids of semisolid topical products. Selecting a representative sample size to describe accurately the in vitro properties of semisolids and to reach enough statistical power to demonstrate similarity between two semisolid topical products is currently challenging. The objective of this work is to establish the number of batches and units per batch to be compared based on different inter-batch and intra-batch variability to demonstrate equivalence in the physical characteristics of the products that ensure a similar microstructure of the semisolid. This investigation shows that the minimum number of batches to be compared of each product is 3 and the minimum number of units per batch could be 6 in the case of low intra- and inter-batch variability. If the products are not identical, i.e., 2.5–5% differences that are expected due to differences in the manufacturing process or the suppliers of excipients, 12 units and 6 batches are needed. If intra- or inter-batch variability is larger than 10%, the number of batches and/or the number of units needs to be increased. As the interplay between inter- and intra-batch variability is complex, the sample size required for each combination of inter- and intra-batch variability and expected difference between products can be obtained in the attached tables.

Dermacosmetic products help alleviate certain conditions. [...]

Background: Stretch marks (Striae gravidarum) are a cutaneous change occurring commonly during pregnancy. A variety of products are available and promoted as ways to prevent or reduce their development, but it is not clear what products are used most commonly. The objective of this study was to identify topical products used during pregnancy to prevent or reduce the development of striae gravidarum. We also explored issues around application of the product, cost incurred and influences on women's decisions to use a product. Methods: In this cross sectional, descriptive survey we collected data from 773 women, via a paper (n = 707) or online (n = 66) questionnaire. Due to missing data in the online survey, 753 women at 36 weeks gestation or more were included in the analyses. Descriptive and inferential statistical analyses were undertaken. Results: Most respondents (n = 589, 78.2 %) indicated that they used a product to prevent or reduce the development of stretch marks during their current pregnancy. A large range of products were used and more than one third of women (n = 210, 36.5 %) had used two or more products. Bio-oil was the most frequently used product (n = 351, 60.9 %) and it was also the most frequently used product among women who used only one product (n = 189, 32.8 %). Conclusions: Many women apply one of the many products available to prevent or reduce the development of striae gravidarum. Bio-oil was the most commonly used product identified in this study. There is a need for high-quality evidence on the effectiveness of Bio-oil and other products. [ABSTRACT FROM AUTHOR]

The potential for many of the commonly used surgical site wound adhesives, skin antiseptic solutions, topical antibiotics, and suture materials to sensitize and subsequently result in allergic contact dermatitis (ACD) has become increasingly recognized within orthopedic surgery. Particularly with subsequent exposure to the offending allergen, the cutaneous allergic reaction may present in a similar fashion to cellulitis, thus making early differentiation between the two etiologies to initiate the appropriate and timely treatment crucial. Recognition of the characteristic appearance and severity of ACD surrounding a surgical wound often drives the initial management. This typically consists of anti-histamines, topical corticosteroids, and possible removal of the offending allergen for low grade findings and oral steroids and prophylactic oral antibiotics for the more severe reactions. Multidisciplinary care, including the expertise of a dermatologist or wound care specialist when faced with this challenging clinical scenario is critical and elective patch testing may be indicated to ascertain the exact allergen involved, particularly in patients with a prior history of wound issues. Finally, any clinical cases of ACD following an orthopedic procedure should be documented in the patient's chart so that exposure can be avoided with any future surgery., Competing Interests: KIG is a paid consultant for Smith & Nephew, Stryker, and a board or committee member for AAOS, American Shoulder and Elbow Surgeons (ASES). CA, ET, LMG, and ECR-M have no disclosures to report., (2023 © BY THE ARCHIVES OF BONE AND JOINT SURGERY.)

Background8T: One of the preservative treatments of knee osteoarthritis is the use of topical medications. This study is aimed to clinically evaluate the effect of topical products containing essential oils of rosemary and lavender herbs on the treatment of patients with osteoarthritis of the knee. Materials and Methods8T: Rosemary and lavender essential oils were prepared by steam distillation method and inserted into the ointment with the hydrophilic base. In this study, 15 patients with knee osteoarthritis were treated with this ointment for three months. The results were assessed using WOMAC and Lequesne indices and were evaluated by the Wilcoxon statistical test. Results: At the week of admission to the hospital, mean WOMAC index was equal to 71.4, mean Lequesne index was equal to 18 and the average time of passing through the distance of fifty feet by patients was equal to 19.4. After 4, 8 and 12 weeks, all these indices significantly decreased (p= 0.05). The WOMAC questionnaire denotative survey also showed that the pain and physical function at the 4th, 8th and 12th weeks were significantly less than the first week of admission (p= 0.05), but there was no significant difference as far as joint stiffness is concerned8T. Conclusion: Topical application of essential oils of rosemary and lavender herbs in a hydrophilic ointment base can be useful as a preservative treatment for the patients with knee osteoarthritis. [ABSTRACT FROM AUTHOR]

A novel method to convert S- and racemic(RS-) ibuprofen(Ibu) into an oily state at ambient temperature(25°C) was developed. Using menthol and aqueous isopropanol(IPA) as melting point depressing agents, the two-phase melt systems(TMSs) of Ibu consisting of a homogeneous oily phase and a homogeneous aqueous phase were obtained. In TMS with a high S-Ibu : menthol ratio and a low IPA content, the oily phase primarily consisted of Ibu and menthol, whereas the majority of the aqueous phase was IPA and buffer. Using this method, the S-Ibu concentration in the oily phase reached as high as 70%(w/w). The compositional phase diagram was obtained using a titration method to study the relationship between the melting states of the solid components and system composition. S- and RS-Ibu showed different phase diagrams, and the maximum concentration of S-Ibu measured in the oily phase of TMS was much greater than that of RS-Ibu. The permeation study of a series of TMS and non-TMS systems showed that S-Ibu penetrated through shed snake skin faster than RS-Ibu, and the contents of IPA and menthol significantly affected the permeation rates of ibuprofen across shed snake skin, which may be attributed to the higher lipophilicity, and thus, higher solubility of S-Ibu in the skin than RS-Ibu. Such results support the use of S-Ibu TMS for topical formulation development. [ABSTRACT FROM AUTHOR]

The purpose of this research was to evaluate different parameters that can influence in vitro drug release from topical dermatological drug products such as creams, gels, and ointments. In vitro release from topical dermatological drug products was carried out by using a static diffusion cell, a synthetic membrane, and an appropriate receptor medium. The receptor medium was mixed by means of a magnetic bar rotated at 400 rpm. Experiments were designed to evaluate the influence of (i) receptor media, (ii) different lots of synthetic membranes, and (iii) agitation on drug release. Release experiments were also carried out to study inter- and intralot variability. The in vitro release test was used to evaluate the marketed glucocorticoid products. Among the parameters studied, the receptor medium was found to be the most important and critical variable that influenced drug release. The release rate ranged between 0.61 and 2.68 μg/cm2/min0.5 for betamethasone dipropionate, depending on the percentage of ethanol in the receptor medium. The drug release was not influenced by agitation or by different lots of synthetic membranes. Very small inter- and intralot variability was observed. These experiments establish the ruggedness of the in vitro diffusion cell test system used for the drug release measurements. [ABSTRACT FROM AUTHOR]

The assessment of skin irritation, and in particular of skin sensitization, has undergone an evolution process over the last years, pushing forward to new heights of quality and innovation. Public and commercial in silico tools have been developed for skin sensitization and irritation, introducing the possibility to simplify the evaluation process and the development of topical products within the dogma of the computational methods, representing the new doctrine in the field of risk assessment.The possibility of using in silico methods is particularly appealing and advantageous due to their high speed and low-cost results.The most widespread and popular topical products are represented by cosmetics. The European Regulation 1223/2009 on cosmetic products represents a paradigm shift for the safety assessment of cosmetics transitioning from a classical toxicological approach based on animal testing, towards a completely novel strategy, where the use of animals for toxicity testing is completely banned. In this context sustainable alternatives to animal testing need to be developed, especially for skin sensitization and irritation, two critical and fundamental endpoints for the assessment of cosmetics.The Quantitative Risk Assessment (QRA) methodology and the risk assessment using New Approach Methodologies (NAM) represent new frontiers to further improve the risk assessment process for these endpoints, in particular for skin sensitization.In this chapter we present an overview of the already existing models for skin sensitization and irritation. Some examples are presented here to illustrate tools and platforms used for the evaluation of chemicals., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Surfactants are the most common inactive ingredients used in topical drug products. Surfactants in topical products play many functional roles such as emulsifiers, permeation enhancers, and solubilizers. This study was aimed to evaluate the influence of incremental change in the concentration of a surfactant (tween 80) on the quality attributes and performance of semisolid topical products. Four creams were prepared using metronidazole as a model drug using the same manufacturing protocol and similar composition except for the concentration of tween 80, which was increased by 5% w/w across SF1 to SF4. The quality attributes like globule size, pH, drying rate, and in-vitro permeation profile were characterized. The critical quality attributes did not differ significantly across the products. However, there was a significant difference in the permeation profile of the products. The permeation flux (J max) varied from SF1 to SF4 (51.25 ± 35.29 to 307.98 ± 138.89 ng/cm2/h, respectively). The reason for the difference in the performance of products despite having consistent quality attributes was investigated. One of the major reasons was found to be the difference in the time course of degree of saturation of drug during the evaporative metamorphosis. This study confirms that the time course of degree of saturation is one of the important quality attributes of the topical product that could influence bioavailability and performance of topical products. [ABSTRACT FROM AUTHOR]

Inter- and intra-batch variability of the quality attributes contribute to the uncertainty for demonstrating equivalent microstructure of post-approval changes and generic/hybrids of semisolid topical products. Selecting a representative sample size to describe accurately the in vitro properties of semisolids and to reach enough statistical power to demonstrate similarity between two semisolid topical products is currently challenging. The objective of this work is to establish the number of batches and units per batch to be compared based on different inter-batch and intra-batch variability to demonstrate equivalence in the physical characteristics of the products that ensure a similar microstructure of the semisolid. This investigation shows that the minimum number of batches to be compared of each product is 3 and the minimum number of units per batch could be 6 in the case of low intra- and inter-batch variability. If the products are not identical, i.e., 2.5–5% differences that are expected due to differences in the manufacturing process or the suppliers of excipients, 12 units and 6 batches are needed. If intra- or inter-batch variability is larger than 10%, the number of batches and/or the number of units needs to be increased. As the interplay between inter- and intra-batch variability is complex, the sample size required for each combination of inter- and intra-batch variability and expected difference between products can be obtained in the attached tables. [ABSTRACT FROM AUTHOR]

Considering the recent regulatory requirements, the overall importance of in vitro release testing (IVRT) methods regarding topical product development is undeniable, especially when addressing particulate systems. For each IVRT study, several hundreds of samples are generated. Therefore, developing rapid reversed-phase high-performance liquid chromatography (RP-HPLC) methods, able to provide a real-time drug analysis of IVRT samples, is a priority. In this study, eight topical complex drug products exhibiting distinct physicochemical profiles were considered. RP-HPLC methods were developed and fully validated. Chromatographic separations were achieved on a XBridgeTM C18 (5 µm particle size, 150 mm × 2.1 mm), or alternatively on a LiChrospher® 100 RP-18 (5 µm particle size, 125 mm × 4.6 mm) at 30 °C, under isocratic conditions using UV detection at specific wavelengths. According to the physicochemical characteristics of each drug, different mobile phases were selected. Irrespective of the drug (hydrocortisone, etofenamate, bifonazole, clotrimazole, acyclovir, tioconazole, clobetasol, and diclofenac) and formulation, retention time values did not exceed 6.5 min. All methods were linear, specific, precise, and accurate at the intraday and interday levels, robust, and stable. These were successfully applied to establish product-specific IVRT profiles, thus providing a key database useful for topical pharmaceutical manufacturers. [ABSTRACT FROM AUTHOR]