scholarly journals Stratum Corneum Sampling to Assess Bioequivalence between Topical Acyclovir Products

2019 ◽  
Vol 36 (12) ◽  
Author(s):  
A. Pensado ◽  
W.S. Chiu ◽  
S. F. Cordery ◽  
E. Rantou ◽  
A. L. Bunge ◽  
...  
Keyword(s):  
Stratum Corneum ◽  
Statistical Power ◽  
Application Site ◽  
Tape Stripping ◽  
Local Skin ◽  
Drug Products ◽  
Single Time Point ◽  
Topical Acyclovir ◽  
Alternative Metrics

Abstract Purpose To examine the potential of stratum corneum (SC) sampling via tape-stripping in humans to assess bioequivalence of topical acyclovir drug products, and to explore the potential value of alternative metrics of local skin bioavailability calculable from SC sampling experiments. Methods Three acyclovir creams were considered in two separate studies in which drug amounts in the SC after uptake and clearance periods were measured and used to assess bioequivalence. In each study, a “reference” formulation (evaluated twice) was compared to the “test” in 10 subjects. Each application site was replicated to achieve greater statistical power with fewer volunteers. Results SC sampling revealed similarities and differences between products consistent with results from other surrogate bioequivalence measures, including dermal open-flow microperfusion experiments. Further analysis of the tape-stripping data permitted acyclovir flux into the viable skin to be deduced and drug concentration in that ‘compartment’ to be estimated. Conclusions Acyclovir quantities determined in the SC, following a single-time point uptake and clearance protocol, can be judiciously used both to objectively compare product performance in vivo and to assess delivery of the active into skin tissue below the barrier, thereby permitting local concentrations at or near to the site of action to be determined.

scholarly journals The Implications of Regulatory Framework for Topical Semisolid Drug Products: From Critical Quality and Performance Attributes towards Establishing Bioequivalence

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 710
Author(s):  
Tanja Ilić ◽  
Ivana Pantelić ◽  
Snežana Savić
Keyword(s):  
Statistical Power ◽  
Failure Modes ◽  
In Vitro Release ◽  
Optimal Number ◽  
Drug Products ◽  
Pharmaceutical Equivalence ◽  
And Performance ◽  
Low Sensitivity

Due to complex interdependent relationships affecting their microstructure, topical semisolid drug formulations face unique obstacles to the development of generics compared to other drug products. Traditionally, establishing bioequivalence is based on comparative clinical trials, which are expensive and often associated with high degrees of variability and low sensitivity in detecting formulation differences. To address this issue, leading regulatory agencies have aimed to advance guidelines relevant to topical generics, ultimately accepting different non-clinical, in vitro/in vivo surrogate methods for topical bioequivalence assessment. Unfortunately, according to both industry and academia stakeholders, these efforts are far from flawless, and often upsurge the potential for result variability and a number of other failure modes. This paper offers a comprehensive review of the literature focused on amending regulatory positions concerning the demonstration of (i) extended pharmaceutical equivalence and (ii) equivalence with respect to the efficacy of topical semisolids. The proposed corrective measures are disclosed and critically discussed, as they span from mere demands to widen the acceptance range (e.g., from ±10% to ±20%/±25% for rheology and in vitro release parameters highly prone to batch-to-batch variability) or reassess the optimal number of samples required to reach the desired statistical power, but also rely on specific data modeling or novel statistical approaches.

scholarly journals Desmoglein Isoform Distribution Affects Stratum Corneum Structure and Function

2001 ◽  
Vol 153 (2) ◽  
pp. 243-250 ◽  
Author(s):  
Peter M. Elias ◽  
Norihisa Matsuyoshi ◽  
Hong Wu ◽  
Chenyan Lin ◽  
Zhi Hong Wang ◽  
...  
Keyword(s):  
Stratum Corneum ◽  
Mucous Membrane ◽  
Water Loss ◽  
Transepidermal Water Loss ◽  
Tape Stripping ◽  
Permeability Barrier ◽  
Differential Distribution ◽  
Desmoglein 3

Desmogleins are desmosomal cadherins that mediate cell–cell adhesion. In stratified squamous epithelia there are two major isoforms of desmoglein, 1 and 3, with different distributions in epidermis and mucous membrane. Since either desmoglein isoform alone can mediate adhesion, the reason for their differential distribution is not known. To address this issue, we engineered transgenic mice with desmoglein 3 under the control of the involucrin promoter. These mice expressed desmoglein 3 with the same distribution in epidermis as found in normal oral mucous membranes, while expression of other major differentiation molecules was unchanged. Although the nucleated epidermis appeared normal, the epidermal stratum corneum was abnormal with gross scaling, and a lamellar histology resembling that of normal mucous membrane. The mice died shortly after birth with severe dehydration, suggesting excessive transepidermal water loss, which was confirmed by in vitro and in vivo measurement. Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes. This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping. These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

scholarly journals In vivo human skin penetration of (–)-epigallocatechin-3-gallate from topical formulations

2014 ◽  
Vol 64 (2) ◽  
pp. 257-265 ◽  
Author(s):  
Santo Scalia ◽  
Valentina Trotta ◽  
Anna Bianchi
Keyword(s):  
Stratum Corneum ◽  
Skin Penetration ◽  
Tape Stripping ◽  
Human Stratum Corneum ◽  
Percutaneous Permeation ◽  
Oil In Water ◽  
Human Volunteers ◽  
Model Oil ◽  
Gel Formulations

Abstract The aim of the study was to examine the effect of topical vehicles on the in vivo human stratum corneum penetration of the antioxidant and skin photoprotective agent (-)-epigallocatechin-3-gallate (EGCG). Model oil-in-water (o/w) emulsion and gel formulations containing 1 % (m/m) EGCG were prepared and subjected to photodegradation studies in order to select excipients that minimize the light instability of EGCG. The optimized emulsion and gel were applied to human volunteers and the EGCG percutaneous permeation was evaluated in vivo by the tape- -stripping technique. No significant differences in the percentage of the applied EGCG dose diffused into the stratum corneum were observed between the o/w emulsion (36.1 ± 7.5 %) and gel (35.5 ± 8.1 %) preparations. However, the amount of EGCG permeated into the deeper region of human stratum corneum was significantly larger for the o/w emulsion compared to the gel. Therefore, the emulsion represents a suitable vehicle for topical delivery of EGCG.

Design and Evaluation of a Self-Adhesive Naproxen-Loaded Film Prepared from a Nanoparticle Dispersion

2006 ◽  
Vol 6 (9) ◽  
pp. 3235-3241 ◽  
Author(s):  
Adriana Ganem-Quintanar ◽  
Marlene Silva-Álvarez ◽  
Rocío Álvarez-Román ◽  
Norma Casas-Alancaster ◽  
Jennyfer Cázares-Delgadillo ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Stratum Corneum ◽  
Fickian Diffusion ◽  
Release Mechanism ◽  
Tape Stripping ◽  
Cellulose Membrane ◽  
Molecular Dispersion ◽  
Calorimetric Studies

Naproxen-loaded nanoparticles were used to prepare, in a one-step process, unilaminar films of Eudragit E-100 (EE-100), avoiding the use of organic solvents and assuring the homogeneity and molecular dispersion of the drug. Nanoparticle films (NP-F) and conventional films (CV-F, prepared by casting of methanolic solutions onto a Teflon disc) were assayed by their mechanical properties, skin adhesivity, and calorimetric studies to compare their behavior. Different proportions of plasticizer (triacetin) were included to evaluate the quality of the films. Film characterization included in vitro drug release studies through a cellulose membrane using Franz-type cells, and in vivo stratum corneum penetration experiments by the tape stripping technique. The results showed that NP-F were semi-transparent to transparent, suggesting a good compatibility between naproxen and EE-100. Differential calorimetric studies (DSC) confirmed a molecular dispersion of naproxen in the EE-100 matrix. Taking into account the mechanical properties of the films, a 20% triacetin concentration can be considered as optimal for both types of films. The in vitro release data obtained from both systems (NP-F and CV-F) followed the Higuchi's model for matrix systems, with the Fickian diffusion (t0.5) being the main release mechanism. Concerning the in vivo penetration studies, no statistical differences were found for the penetrated amount of naproxen across the stratum corneum and the depth of penetration for the two films and between the three contact times (2, 4, and 6 h). The films formulated from nanoparticle dispersions (NP-F) were shown to be effective for the transdermal administration of naproxen, and can be considered as an interesting alternative for the preparation of films with several technological advantages.

scholarly journals Interleukin-8 Levels in the Stratum Corneum as a Biomarker for Monitoring Therapeutic Effect in Atopic Dermatitis Patients

2021 ◽  
pp. 1-15
Author(s):  
Susumu Murata ◽  
Sakae Kaneko ◽  
Eishin Morita
Keyword(s):  
Atopic Dermatitis ◽  
Topical Corticosteroid ◽  
Stratum Corneum ◽  
Corticosteroid Treatment ◽  
Skin Inflammation ◽  
Interleukin 8 ◽  
Tape Stripping ◽  
Therapeutic Effects ◽  
Local Skin ◽  
Before And After

<b><i>Introduction:</i></b> The stratum corneum contains several growth factors and cytokines that are synthesized in keratinocytes. We previously reported that the amount of interleukin-8 in the stratum corneum (scIL-8) is related to the severity of local skin inflammation in atopic dermatitis (AD). However, it is unknown whether scIL-8 levels reflect pharmacologic responses to a therapeutic intervention in AD patients. Therefore, in this study, we aimed to investigate whether the improvement of dermatitis in AD is correlated with scIL-8 levels before and after topical corticosteroid treatment. <b><i>Methods:</i></b> Stratum corneum samples were collected from 22 AD patients using the noninvasive tape-stripping method before treatment, 2 weeks after topical treatment, and 4–6 weeks after treatment. <b><i>Results:</i></b> scIL-8 levels on the forearm reduced significantly from 790 ± 348 pg/mg before treatment to 163 ± 68 pg/mg 2 weeks after treatment and 100 ± 37 pg/mg 4–6 weeks after corticosteroid treatment. scIL-8 levels on the abdomen also reduced significantly from 902 ± 391 to 142 ± 38 pg/mg at the end of study. The reduction in scIL-8 levels was associated with the improvement in local skin severity in AD. We also found that scIL-8 levels, along with blood biomarker levels (serum thymus and activation-regulated chemokine, lactate dehydrogenase, and %eosinophil), decreased significantly after the treatment. <b><i>Conclusion:</i></b> The scIL-8 concentration decreases with improvements in skin symptoms in AD patients after topical corticosteroid treatment; thus, it may be a suitable biomarker for monitoring therapeutic effects in AD patients.

scholarly journals Polymeric Films Loaded with Vitamin E andAloe verafor Topical Application in the Treatment of Burn Wounds

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Gabriela Garrastazu Pereira ◽  
Sílvia Stanisçuaki Guterres ◽  
Anna Giulia Balducci ◽  
Paolo Colombo ◽  
Fabio Sonvico
Keyword(s):  
Vitamin E ◽  
Stratum Corneum ◽  
Aloe Vera ◽  
Polymeric Films ◽  
Tape Stripping ◽  
Skin Damage ◽  
Burn Wounds ◽  
Vitamin E Acetate ◽  
Deep Layers

Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such asAloe veraand vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containingAloe veraand vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. Thein vivoexperiments with tape stripping indicated an effective accumulation in thestratum corneumwhen compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of thestratum corneumwhen the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate andAloe veracould be an innovative therapeutic system for the treatment of burns.

scholarly journals Liposome percutaneous penetration in vivo

2017 ◽  
Vol 1 ◽  
pp. 239784731772319 ◽  
Author(s):  
A Lymberopoulos ◽  
C Demopoulou ◽  
M Kyriazi ◽  
MS Katsarou ◽  
N Demertzis ◽  
...  
Keyword(s):  
Stratum Corneum ◽  
Rhodamine B ◽  
Transdermal Delivery ◽  
Penetration Enhancers ◽  
Percutaneous Penetration ◽  
Hairless Mice ◽  
Liposomal Form ◽  
Multilamellar Vesicles ◽  
Small Unilamellar Vesicles

Objectives: Liposomes are reported as penetration enhancers for dermal and transdermal delivery. However, little is known about their percutaneous penetration and as to at which level they deliver encapsulated drugs. The penetration of multilamellar vesicles (MLVs) and small unilamellar vesicles (SUVs), in comparison to one of their lipid components, was investigated. Methods: Using the fluorescent lipid, Lissamine Rhodamine B-PE (R), as a constituent, MLV and SUV liposomes were prepared, tested, and R, MLV, or SUV were applied in vivo on the back of hairless mice. Absorption of each was evaluated at the levels of stratum corneum, living skin, and blood by fluorometry. Results: Penetration of the lipid R in stratum corneum in the nonliposomal form exceeded that in the liposomal form and only R penetrates the living skin in a statistically significant manner. No statistical significant absorption into blood was observed with either form. Conclusions: Liposomes size did not play an important role in penetration to stratum corneum. The lipid constituent in the nonliposomal form penetrated at higher rates into stratum corneum and living skin. Even though these liposomes entered stratum corneum, they were not significantly absorbed into viable skin or blood.

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