Diffusion Cell System Research Articles

Impact of Skin Decontamination Wipe Solutions on the Percutaneous Absorption of Polycyclic Aromatic Hydrocarbons.

Firefighter occupational exposures were categorized as a class 1 (known) carcinogen by the International Agency for Research on Cancer in 2022. As a result, firefighters have become heavily focused on identifying effective and easy to implement decontamination strategies to reduce their chemical exposures. Skin decontamination using wipes post-exposure is one decontamination strategy that every firefighter has available to them. However, firefighters have expressed concerns over the ingredients in the wipe solution increasing dermal absorption. The goal of this study was to determine if the ingredients in skin decontamination wipe solution had any enhancement effect on the dermal absorption of phenanthrene. To determine any enhancement effects, the additive solution of four skin decontamination wipe products was applied to porcine skin 15 min after chemical dosing. The absorption of phenanthrene was tested in vitro using a flow-through diffusion cell system over eight hours. The wipe solution effects on dermal absorption were determined by measuring multiple absorption characteristics including cumulative absorption (µg/cm2), absorption efficiency (% dose absorbed), lag time (minutes), flux (µg/cm2/h), diffusivity (cm2/h), and permeability (cm/h). No penetration enhancement effects were observed in any of the skin decontamination wipe solutions tested; rather, all wipe solutions decreased the absorption of phenanthrene. Slight differences in cumulative absorption among two pairings of skin decontamination wipe solutions, wipes 1 and 3 vs. wipes 2 and 4, were observed, indicating that some ingredients may impact dermal absorption. These findings show that firefighters should continue using skin decontamination wipes to reduce their dermal exposures to fireground contaminants with little concern of increasing the absorption of phenanthrene.

LP-52 In vitro percutaneous absorption of dehydroacetic acid and benzoic acid, preservative cosmetic ingredients, from mini-pig skin using the Franz diffusion cell system

LP-52 In vitro percutaneous absorption of dehydroacetic acid and benzoic acid, preservative cosmetic ingredients, from mini-pig skin using the Franz diffusion cell system

Human skin absorption of three plasticizers: Diisononyl-1,2-cyclohexanedicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP), and di(2-ethylhexyl) adipate (DEHA)

Alternative plasticizers such as diisononyl-1,2-cyclohexanedicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP), and di(2-ethylhexyl) adipate (DEHA) are progressively replacing phthalates in many consumer and professional products because of adverse effects on reproduction associated with some phthalates. Human exposures to these phthalate substitutes can occur through ingestion, skin absorption and inhalation. Skin uptake can lead to greater concentration at the target organs compared to ingestion because the skin exposure route bypasses the first-pass effect. Skin absorption studies are almost absent for these alternative plasticizers. We therefore wanted first, to characterize skin absorption of a mixture containing DINCH, DEHA and DEHTP in vitro using a flow-through diffusion cell system with ex vivo human skin, quantifying their respective monoester metabolites (mono-isononyl-cyclohexane-1,2-dicarboxylate (MINCH), mono-2-ethylhexyl adipate (MEHA), mono-2-ethylhexyl terephthalate (MEHTP), respectively); second, to validate these results by exposing five human volunteers to this mixture on their forearm and quantifying the corresponding urinary metabolites (including the monoesters and their oxidation products). Our study showed that two of these alternative plasticizers, DEHTP and DINCH, did not permeate skin showing as quantifiable metabolite levels in vitro and only traces of DEHA were quantified as its monoester metabolite, MEHA. Permeation coefficient (Kp) 0.06 and 55.8*10−7 cm/h for neat and emulsified DEHA, respectively, while the permeation rate (J) remained low for both (0.005 and 0.001 µg/cm2/h, respectively). Participants exposed to a mixture of these three plasticizers did not have noteworthy urinary concentrations of their respective metabolites after 24 hours post-application. However, the alternative plasticizer mixture was completely absorbed after six hours post-application on the forearms of the human volunteers, and the urinary elimination curves showed a slight increase after 24 hours post-application. Further studies on skin absorption of these substances should follow the urinary elimination kinetics of these metabolites more than 24 hours post-application. We also recommend quantifying the parent compounds in the in vitro diffusion experiments.

Comparison of permeability of topical Cream drug through polymer synthetic membranes of different structures using Franz Cell diffusion test

In this study, in-vitro release experiments were performed using a Franz Diffusion Cell system for Terbinafine Hydrochloride, which is used in the treatment of various fungal infections in the skin caused by many susceptible dermatophytes. In order to evaluate TH transdermally, it was aimed to compare the permeability between polymeric membranes synthesized with polyvinyl alcohol and chitosan mixtures and commercial membranes. In the transdermal drug delivery system calculations, the Fick Diffusion Law was modified and the obtained data were compared. The study was evaluated according to the USP <1724> topical drug products in semisolid form - performance tests. A new high-performance liquid chromatography method was validated for the assay of TH released into the receptor medium in accordance with the ICH guideline. According to the results obtained during the validation process, the limit of detection value was calculated as 0.005 µg/mL and the limit of quantification value was 0.013 µg/mL. Since polymer-based synthetic membranes provide permeability according to molecular size, properties and the ideal environment for measuring and analyzing the diffusion rate of a compound, in experiments conducted using membranes of different structures, the permeability profiles of selected polymer synthetic membranes were statistically evaluated. It has been noted that the hydroxyl groups in PVA and the hydrophilic CS-g-PNDMAAm graft copolymer act at varying rates to enhance or reduce the permeability across the membrane by promoting its diffusion. NaY zeolite has been shown to function as an adsorbent against the medication, lessening the impact of hydrophilic PVA without supplying permeability.

Evaluation of emergency skin decontamination protocols in response to an acid attack (vitreolage)

The incidence of “acid attacks” (vitreolage) is a global concern, with those affected often receiving lifelong medical care due to physical and psychological damage. The purpose of this study was to evaluate the effectiveness of several emergency skin decontamination approaches against concentrated (>99 %) sulphuric acid and to identify the effective window of opportunity for decontamination. The effects of four decontamination methods (dry, wet, combined dry & wet and cotton cloth) were assessed using an in vitro diffusion cell system containing dermatomed porcine skin. Sulphuric acid (H2SO4) was applied to the skin with decontamination protocols performed at 10 s, 30 s, 8 min, and 30 min post exposure. Skin damage was quantified by tritiated water (3H2O) penetration, receptor fluid pH and photometric stereo imaging (PSI), with quantification of residual sulphur (by SEM-EDS) to determine overall decontamination efficiency. Skin translucency (quantified by PSI) demonstrated a time-dependent loss of dermal tissue integrity from 10 s. Quantification of dermal sulphur content confirmed the rapid (exponential) decrease in decontamination efficiency with time. The pH of the water effluent indicated complete neutralisation of acid from the skin surface after 90 s of irrigation. Wet decontamination (either alone or immediately following dry decontamination) was the most effective intervention evaluated, although no decontamination technique was statistically effective after 30 s exposure to the acid. These data demonstrate the time-critical consequences of dermal exposure to concentrated sulphuric acid: we find no practical window of opportunity for acid decontamination, as physical damage is virtually instantaneous.

Hydroxytyrosol permeability comparisons and strategies to improve hydroxytyrosol stability in formulations

There has been a growing interest in hydroxytyrosol (HT) due to its powerful antioxidant and free-radical scavenging properties when added to formulations such as pharmaceuticals and cosmetics. To study the stability and transdermal properties of hydrogels and creams (HT-based formulations), a high-performance liquid chromatography method was developed for determining HT. In the Franz diffusion cell system, both hydrogel and cream show a rapid and similar penetration profile through the Bama miniature pig skin. However, the Strat-M® membrane exhibits slightly lower permeability and is selective to different formulations; that is, the cream has a permeability value of 10.69%, while the hydrogel has a value of 5.27%. The dynamics parameters from the permeation assays indicate that the model using the Strat-M® membrane can be used as a screening tool to evaluate the skin uptake and permeation efficacy of different formulations. Adding 3-O-ethyl-L-ascorbic acid to HT-based formulations can effectively prevent discoloration under prolonged high-temperature storage, while combining multiple antioxidants delays degradation most effectively. This study provides novel ideas for functional formulation optimization to enhance the realism and reproducibility of cosmetic products containing HT and provides scientific evidence for the production, packaging, shelf life, storage, and transportation of products.

The Formulation of Dermato-Cosmetic Products Using Sanguisorba minor Scop. Extract with Powerful Antioxidant Capacities

There has been a significant increase in the use of botanical resources for the formulation of topical products designed for medicinal and cosmetic applications. Sanguisorba minor Scop., a botanical species, exhibits a variety of properties and has significant potential for applications in the field of cosmetics. The aim of this study was to formulate topical preparations, incorporating an extract derived from the plant S. minor Scop. comprising a combination of roots, leaves, and flowers. In the initial phase, a total of seven combinations were prepared using extracts derived from the roots, leaves, and flowers of S. minor Scop. (v/v/v). These combinations were subsequently subjected to evaluation for their antioxidant capacity using four distinct methods: 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC), and Trolox equivalent antioxidant capacity (TEAC). An extract of plant organs in a ratio of 1:2:1 (v/v/v), which had a strong antioxidant capacity and demonstrated synergistic effects according to the DPPH, TEAC, and CUPRAC assays (with values of 1.58 ± 0.1, 1.18 ± 0.09, and 1.07 ± 0.07, respectively), was selected for inclusion in three dermato-cosmetic products (hydrogel, emulgel, and cream). All the prepared preparations were evaluated in terms of topical formulation attributes and organoleptic characteristics. The testing of dermato-cosmetic products included assessments of their topical formulation properties and organoleptic characteristics. The hydrogel, emulgel, and cream exhibited varying degrees of stretchability. In addition, a study was carried out to assess the in vitro release of polyphenols from the cosmetic formulations using a Franz diffusion cell system. The results showed that the emulgel containing the extract of S. minor Scop. had the highest and most significant release of polyphenols, with a release rate of 84.39 ± 1.01%. This was followed by the hydrogel and cream, which had release percentages of 80.52 ± 0.89 and 75.88 ± 0.88, respectively, over an 8 h period. Thus, for the first time in the literature, a topical cosmetic product with high antioxidant potential containing S. minor Scop. extract was developed and optimized.

Development of a tadalafil transdermal formulation and evaluation of its ability to in vitro transdermal permeate using Strat-M® membrane

Tadalafil (TDF) has low water solubility, high intestinal permeability and belongs to the Biopharmaceutics Classification System (BCS) Class II. Due to high intestinal permeability, only oral administration (tablets) and oral thin film formulations have been developed. Therefore, it is necessary to develop various formulations, such as external formulations and transdermal absorption formulations requested by patients. The purpose of this study is to improve the solubility and skin permeability of TDF, and to develop a novel transdermal formulation with secured stability over time. The research strategy is to determine solvents that will improve TDF solubility and to screen substances that will enhance TDF permeability. Skin penetration tests were simulated by using a Strat-M® membrane in Franz diffusion cell systems. The optimal formulation (F1, consisting of TDF/HDTMA-Br at a ratio of 1:10 [weight/weight] in DPG) observed the highest permeability compared to all formulations in PBS (pH 7.4). Changes in thermal property of F1 formulation was observed and maintained its stability over 12 months including drug content (μg/mL), appearance, pH, and permeation (μg/cm2). In conclusion, DPG played a supported role in improving both TDF solubilization and permeability, whereas HDTMA-Br played a key role in enhancing permeability. It is thought that these results will be supplemented in the future to conduct research and experiments on humans.

Enhancing Transdermal Delivery of Ketorolac Tromethamine Using Dimethyl Sulfoxide: A Systematic Study

Transdermal delivery systems which are directly applied on the skin serve as a substitute for oral drug delivery avoiding first-pass metabolism. The problem of drug penetration through the skin definitely remains one of the biggest issues. This study ascertains the likelihood of DMSO, a penetration enhancer to boost KT, one of the most powerful analgesics. Through DMSO amount variations on KT were prepared and then permeation was studied by means of a Franz Diffusion cell system on rat skin. It increased the permeability coefficient and flux with the increase of the DMSO level, and it reached the maximum when the DMSO concentration was 0. 1. Further understanding of mechanisms and optimal DMSO concentrations seem to be necessary for future development of this promising anticancer treatment approach. Briefly summarizing, DMSO does seem to meet the demands, according to the transdermal drug delivery efficacy standpoint, being safe and convenient for topical application.

Assessment of Apple Peel Barrier Effect to Pesticide Permeation Using Franz Diffusion Cell and QuEChERS Method Coupled with GC-MS/MS.

In this study, a new approach to pesticide permeation through the apple peel into the pulp is discussed. The tested compounds can be classified, based on mode of action, as systemic (boscalid, cyprodinil, pirimicarb, propiconazole and tebuconazole) or contact (captan, cypermethrin and fludioxonil) pesticides. The barrier effect was assessed using a Franz flow-type vertical diffusion cell system. A residue analysis was performed using a modified quick, easy, cheap, efficient, rugged and safe (QuEChERS) extraction method coupled to gas chromatography with tandem mass spectrometry (GC-MS/MS). The limits of detection (LODs) ranged between 2.6 µg kg-1 (pirimicarb) and 17 µg kg-1 (captan), with the coefficient of variability (CV) lower than 6%, while recoveries ranged from 85% (boscalid) to 112% (captan) at 0.1 and 1 mg kg-1 spiked levels. The highest peel penetration was observed for pirimicarb, captan and cyprodinil, with cumulative permeations of 90, 19 and 17 µg cm-2, respectively. The total absorption was in the range from 0.32% (tebuconazole) to 32% (pirimicarb). Only cypermethrin was not quantitatively detected in the pulp, and its use can be recommended in crop protection techniques. The obtained results indicate that molecular weight, octanol-water partition coefficient and water solubility are important parameters determining the process of pesticide absorption.

A Preliminary Study on the Release of Bioactive Compounds from Rice Starch Hydrogels Produced by High-Pressure Processing (HPP).

This work aimed to carry out a preliminary study on the release of bioactive compounds loaded into starch-based hydrogels produced by high-pressure processing (HPP). As a study case, the experiments were carried out on rice starch HPP hydrogels. Rice starch (20% w/w) and green tea extract (2% w/w), suspended in distilled water, were treated by HPP at processing conditions enabling starch gelatinisation, namely 600 MPa for 15 min at room temperature. Additional experiments were carried out on samples that were further loaded with glycerol (5% w/w). Gel formation was assessed by analysing the gelatinisation extent, structuring level, and swelling power of the samples. At the processing conditions utilised, stable hydrogels were obtained even in the presence of the extract and/or the glycerol in the starch suspension. As expected, the colour of the hydrogels formed was affected by the addition of green tea extract in the starch solution. HPP starch hydrogels were characterised by Fourier transform infrared spectroscopy (FT-IR) to determine the interactions between the different compounds utilised in the formulation. Moreover, the release kinetics of bioactive compounds from HPP rice starch hydrogels was evaluated using a vertical Franz diffusion cells system, simulating a transdermal pattern. The diffusion of bioactive compounds was measured spectrophotometrically and via HPLC analysis. A controlled release of bioactive compounds from the hydrogel structure was detected, suggesting that small molecules, such as polyphenols, positively interacted with the rice starch HPP hydrogel network that allowed a smooth and constant release of these bioactive compounds over time.

Preparation, Characterization and ex vivo Skin Permeability Evaluation of Type I Collagen-Loaded Liposomes.

In the present study, we prepared collagen liposomes with the addition of polyol, which is expected to not only increase the solubility of collagen but also improve skin penetration. Collagen liposomes were prepared by the film dispersion method, and their characteristics, integrity and biosafety were evaluated by Fourier transform infrared spectroscopy (FTIR), UV-VIS spectroscopy, polyacrylamide gel electrophoresis (SDS-PAGE), dynamic light scattering (DLS) and transmission electron microscope (TEM). The transdermal absorption of collagen and collagen liposomes were tested by an ex vivo horizontal Valia-Chien diffusion cell system. We first demonstrated that collagen extracted from bovine Achilles tendon was type I collagen. The results of DLS measurement and TEM observation showed that the collagen liposomes were spherical in shape with average diameter (75.34±0.93 nm) and maintained high stability at low temperature (4°C) for at least 42 days without toxicity. The encapsulation rate of collagen liposomes was 57.80 ± 0.51%, and SDS-PAGE analysis showed that collagen was intact in liposomes. Finally, permeability studies indicated that the collagen-loaded liposomes more easily penetrated the skin compared to collagen itself. This study proposed a new method to improve the bioavailability and permeability of bovine type I collagen, which improves the applicability of collagen in biomedicine, cosmeceuticals and pharmaceutical industries.

Silk peptide-hyaluronic acid based nanogels for the enhancement of the topical administration of curcumin.

The present study focused on the development of Cur-loaded SOHA nanogels (Cur-SHNGs) to enhance the topical administration of Cur. The physiochemical properties of Cur-SHNGs were characterized. Results showed that the morphology of the Cur-SHNGs was spherical, the average size was 171.37 nm with a zeta potential of −13.23 mV. Skin permeation experiments were carried out using the diffusion cell systems. It was found that the skin retention of Cur-SHNGs was significantly improved since it showed the best retention value (0.66 ± 0.17 μg/cm2). In addition, the hematoxylin and eosin staining showed that the Cur-SHNGs improved transdermal drug delivery by altering the skin microstructure. Fluorescence imaging indicated that Cur-SHNGs could effectively deliver the drug to the deeper layers of the skin. Additionally, Cur-SHNGs showed significant analgesic and anti-inflammatory activity with no skin irritation. Taken together, Cur-SHNGs could be effectively used for the topical delivery of therapeutic drugs.

In-vitro Tests of Topical Skin Protectants using a Flow-Through Diffusion Cell System Containing Excised Hairless Mouse Skin

Highly toxic chemical warfare agents(CWA) could be used in chemical warfare and terrorism. The protection of skin is crucial for civilians and soldiers, because the primary routes of exposure to CWA are inhalation and skin absorption. Thus, topical skin protectants(TSP) have been studied and developed in many countries to complement protective equipments. In this study, &lt;i&gt;in-vitro&lt;/i&gt; test procedure was optimized and established using a flow-through diffusion cell system containing excised hairless mouse skin in an attempt to assess the effectiveness of various TSP formulations against nerve agent simulants. In addition, the test results on the formulations including the ingredients used in SERPACWA(Skin Exposure Reduction Paste Against Chemical Warfare Agent) and IB-1(TSP of Israel) were included, indicating that the formulations with perfluorinated compounds were more effective than the glycerin-based formulations.

Impact of solvent dry down, vehicle pH and slowly reversible keratin binding on skin penetration of cosmetic relevant compounds: I. Liquids

To measure progress and evaluate performance of the newest UB/UC/P&G skin penetration model we simulated an 18-compound subset of finite dose in vitro human skin permeation data taken from a solvent-deposition study of cosmetic-relevant compounds (Hewitt et al., J. Appl. Toxicol. 2019, 1–13). The recent model extension involved slowly reversible binding of solutes to stratum corneum keratins. The selected subset was compounds that are liquid at skin temperature. This set was chosen to distinguish between slow binding and slow dissolution effects that impact solid phase compounds. To adequately simulate the physical experiments there was a need to adjust the evaporation mass transfer coefficient to better represent the diffusion cell system employed in the study. After this adjustment the model successfully predicted both dermal delivery and skin surface distribution of 12 of the 18 compounds. Exceptions involved compounds that were cysteine-reactive, highly water-soluble or highly ionized in the dose solution. Slow binding to keratin, as presently parameterized, was shown to significantly modify the stratum corneum kinetics and diffusion lag times, but not the ultimate disposition, of the more lipophilic compounds in the dataset. Recommendations for further improvement of both modeling methods and experimental design are offered.

Pharmacokinetics and the Dermal Absorption of Bromochlorophene, a Cosmetic Preservative Ingredient, in Rats.

The cosmetic industry has flourished in recent years. Accordingly, the safety of cosmetic ingredients is increasing. Bromochlorophene (BCP) is a commonly used cosmetic preservative. To evaluate the effects of BCP exposure, in vitro dermal absorption and in vivo pharmacokinetic (PK) studies were conducted using gel and cream formulations. The Franz diffusion cell system and rat dorsal skin were used for tests according to the Korea Ministry of Food and Drug Safety guidelines for in vitro skin absorption methods. After the dermal application (1.13 mg/cm2) of BCP in the gel and cream formulations, liquid chromatography–mass spectrometry (LC–MS/MS) was used to evaluate the amount of BCP that remained unabsorbed on the skin (WASH), and that was present in the receptor fluid (RF), stratum corneum (SC), and (epi)dermis (SKIN). The total dermal absorption rate of BCP was 7.42 ± 0.74% for the gel formulation and 1.5 ± 0.9% for the cream formulation. Total recovery in an in vitro dermal absorption study was 109.12 ± 8.79% and 105.43 ± 11.07% for the gel and cream formulations, respectively. In vivo PK and dermal absorption studies of BCP were performed following the Organization for Economic Cooperation and Development guidelines 417 and 427, respectively. When intravenous (i.v.) pharmacokinetics was performed, BCP was dissolved in glycerol formal and injected into the tail vein (n = 3) of the rats at doses of 1 and 0.2 mg/kg. Dermal PK parameters were estimated by the application of the gel and cream formulations (2.34 mg/kg of BCP as an active ingredient) to the dorsal skin of the rats. Intravenous and dermal PK parameters were analyzed using a non-compartmental method. The dermal bioavailability of BCP was determined as 12.20 ± 2.63% and 4.65 ± 0.60% for the gel and cream formulations, respectively. The representative dermal absorption of BCP was evaluated to be 12.20 ± 2.63% based on the results of the in vivo PK study.

Azelaic acid loaded chitosan and HPMC based hydrogels for treatment of acne: formulation, characterization, in vitro-ex vivo evaluation

In this study, hydrogels containing azelaic acid were developed using chitosan or HPMC (1–7%) for local treatment of acne vulgaris. Physicochemical properties such as viscosity, pH and mechanical properties were evaluated. In vitro release and ex vivo permeability studies were performed using the Franz diffusion cell system. The pH of the hydrogels was highly compatible with the skin pH and varied between 4.38 and 5.84. The cumulative release percentages of the hydrogels at the end of 6 hours were 65–78%, whereas the marketed product yielded 50% drug release. According to the ex vivo permeability results, azelaic acid accumulated in the skin was found to be 9.38 ± 0.65% (marketed cream), 19.53 ± 1.06% (K3), 10.96 ± 1.91% (H6). The antiacne studies with Cutibacterium acnes revealed that K3 (29.45 ± 0.95) and H6 (32.35 ± 0.15) had higher inhibition zones compared to the marketed cream (24.50 ± 0.90). Additionally, the gels were found to be highly stable as a result of the stability studies for 6 months. Among the hydrogels that were prepared based on experimental findings, K3 (3% Chitosan) and H6 (6% HPMC) represented elevated in vitro release profile, higher permeability and increased antiacne activity. The findings of this research suggest that the developed hydrogels might be an alternative to the marketed product.

A novel dermal delivery system using natural spicules for cosmetics and therapeutics.

Dermal delivery is versatile in therapeutics as well as cosmetics in pursuit of enhancing safety/efficacy and alleviating pain/fear to alternate oral/injective administrations. Natural siliceous spicules offer a potential approach via simple topical medications to circumvent poor penetrations through the skin barrier by loading, carrying, and releasing the active ingredients in a highly efficient and controlled manner. The delivery of ingredients loaded on spicules is assessed to improve the dermal efficacy compared to simple topical treatments. First, needle-like spicules were isolated from natural freshwater sponges. Then, the active ingredient was loaded via liposome formations. Finally, the dermal efficiency was evaluated. Natural siliceous spicules were purified, sorted, and fully characterized to appear 250μm of length and 12μm of diameter on average. A model ingredient, pectolinarin, was efficiently loaded onto the internal space of spicules via lecithin-based liposome formations. The penetration was visualized using a porcine skin sample with a fluorescent dye and assessed quantitatively by a Franz diffusion cell system. Dermal absorption rate was measured 73.4%, while the percutaneous penetration rate was 2.2%. The release pattern turned out a simple diffusion analyzed by Fick's law and Higuchi model. The liposomes loaded onto spicules were further stabilized by a hydrophobic capsulation, which may benefit the overall efficacy of the ingredient. A novel dermal delivery system is beneficial to improve the topical efficacy of biologically active ingredients. The outcomes shed a light upon developing skin-protective/improving cosmetics and therapeutics with enhanced performance.

Study for Evaluation of Hydrogels after the Incorporation of Liposomes Embedded with Caffeic Acid.

Caffeic acid (CA), a phenolic acid, is a powerful antioxidant with proven effectiveness. CA instability gives it limited use, so encapsulation in polymeric nanomaterials has been used to solve the problem but also to obtain topical hydrogel formulas. Two different formulas of caffeic acid liposomes were incorporated into three different formulas of carbopol-based hydrogels. A Franz diffusion cell system was used to evaluate the release of CA from hydrogels. For the viscoelastic measurements of the hydrogels, the equilibrium flow test was used. The dynamic tests were examined at rest by three oscillating tests: the amplitude test, the frequency test and the flow and recovery test. These carbopol gels have a high elasticity at flow stress even at very low polymer concentrations. In the analysis of the texture, the increase of the polymer concentration from 0.5% to 1% determined a linear increase of the values of the textural parameters for hydrogels. The textural properties of 1% carbopol-based hydrogels were slightly affected by the addition of liposomal vesicle dispersion and the firmness and shear work increased with increasing carbomer concentration.

Topical NSAIDs for acute local pain relief: in vitro characterization of drug delivery profiles into and through human skin

Objective The efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs) relates not only to the individual NSAID used but also to differences in formulation design. The aim of this study was to investigate the fundamental differences in ibuprofen and diclofenac drug delivery vehicles, specifically gels and plasters, compared to a recently launched 200 mg ibuprofen medicated plaster and characterize the resulting dermatologic–pharmacokinetic profiles into and through ex vivo human skin layers. Methods In vitro skin permeation testing over 24 h and sacrificial timepoint penetration experiments (at 1, 4, 8, 12, and 24 h) were conducted using an automated flow-through diffusion cell system. The amount of drug delivered to the epidermis, dermis, and receptor solution (representing deeper tissue) was determined by liquid chromatography-tandem mass spectrometry. Skin protein binding of ibuprofen and diclofenac was investigated by spiking skin homogenate with increasing concentrations of each drug and determining the fraction unbound. Results Differences were observed in the amount of drug recovered at sacrificial timepoints and rate at which drug was delivered to the target site between plaster and gel formulations of ibuprofen and diclofenac and between plaster formulations of the same drug (ibuprofen). While the amount of drug quantified at sacrificial timepoints did not necessarily determine in vivo flux rates, differences in drug distribution within the skin layers indicated where drug reservoirs were formed. Conclusions These findings highlight the importance of intelligent formulation design in determining NSAID delivery through skin layers. Further work is required to quantify drug delivery into deeper tissues and the resultant local anti-inflammatory effects.