Skin Permeation Profiles Research Articles

Thymol-Loaded Polymeric Nanocapsules’ Repellent Activity on Nymphs of Rhipicephalus sanguineus Sensu Lato

Thymol-loaded polymeric nanocapsules were developed in this study to control volatilization and drug release for repellent application on Rhipicephalus sanguineus nymphs. Policaprolactone-loaded nanocapsules were prepared and characterized by diameter, PdI, zeta potential, pH, entrapment efficiency, and thymol content. Moreover, drug release, skin permeation profile, and repellent activity were evaluated. Nanocapsules showed a mean diameter of 195.7 ± 0.5 nm, a PdI of 0.20 ± 0.01, a zeta potential of −20.6 ± 0.3 mV, a pH of 4.7 ± 0.1, and an entrapment efficiency and a thymol content of 80.1 ± 0.1% and 97.9 ± 0.2%, respectively. The nanosystem progressively released 68.6 ± 2.3% of the thymol over 24 h, demonstrating that it can control drug release. Thymol-loaded nanocapsules showed less epidermis penetration upon skin application than pure thymol (control). Moreover, nanocapsules showed 60–70% repellency for 2 h against Rhipicephalus sanguineus nymphs. Thus, the nanocapsules proved to be a promising alternative for use as an arthropod repellent.

Topical drug delivery by Sepineo P600 emulgel: Relationship between rheology, physical stability, and formulation performance

The objective of this present work was to develop and optimize oil-in-water (O/W) emulsion-based gels, namely emulgels that allow maximum topical drug delivery while having desired microstructure and acceptable physical stability. Emulgels containing 2.0 wt% lidocaine were prepared using various concentrations (0.75–5.0 wt%) of Sepineo P600. Their droplet size distribution, physical stability, rheological behaviors, in vitro drug release, and skin permeation profiles were evaluated. Results show that the concentration of Sepineo P600 significantly influenced the microstructure, rheology, and physical stability of the emulgel formulations. The physico-chemical properties also reveals that at least 1.0 wt% Sepineo P600 was needed to produce stable emulgel formulations. All formulations exhibited non-Newtonian shear-thinning properties which are desirable for topical applications. Both the release and permeation rates decreased with increasing viscosity and rigidity of the formulation. The lower the complex modulus of the emulgels, the higher the steady-state flux of the drug through the skin. Adding Sepineo P600 to emulgel systems resulted in increased rheological properties, which in turn slowed the diffusion of the drug for in vitro release. Although as expected skin permeation was rate limiting since in vitro release was 3 to 4 log-fold faster than skin flux. However, an interesting finding was that the derived skin/vehicle partition coefficient suggested the ionic interaction between lidocaine and Sepineo polymer reducing the free drug, i.e., thermodynamic activity and hence the flux with increasing Sepineo P600 concentration. Overall, this study has provided us with valuable insights into understanding the relationship between the microstructure (rheology), physical stability and skin drug delivery properties which will help to design and optimize topical emulgel formulations.

Development of an Auraptene-Loaded Transdermal Formulation Using Non-ionic Sugar Ester Surfactants.

Auraptene (Aur) is a naturally occurring monoterpene coumarin ether that exhibits numerous therapeutic properties. Its high lipophilicity and low skin penetration, however, limit its potential application for local and transdermal delivery. Biocompatible non-ionic sugar esters (SEs) possess beneficial properties for the development of transdermal formulations in delivering pharmaceutically challenging molecules such as graphene and Aur. In the present study, we conducted a series of experiments to demonstrate the effect of several previously unstudied SEs on the skin permeation and distribution of Aur by preparing gel- and dispersion-type formulations. Skin permeation and deposition experiments were conducted using a Franz diffusion cell with rat skin as the membrane. The dispersion-type formulations prepared using SEs had higher entrapment efficiency, as well as better skin permeation and retention profiles. The dispersion-type formulation containing sucrose palmitate (sSP) exhibited the highest skin permeation over 8 h. Notably, the enhancement effects on Aur concentration in full-thickness skin after the application of the dispersion-type formulation was higher than those of the control formulation. These results indicated that the prepared formulation has potential for use in the transdermal delivery of Aur in pharmaceutical and cosmetic products.

Zeofilters for potentially innovative sunscreen products: formulation, stability and spectroscopic studies

Exposure to both UVA and UVB radiation from the sun stands as the primary cause of skin cancers, contributing to the escalating yearly count of diagnosed cases. Sunscreen products, (i.e. organic and inorganic UV filters) have become ubiquitous in personal-care products, packaging, plastics, dyes, and many other sectors. Ideal UV filters should be photostable and dissipate the absorbed energy efficiently. However, most organic UV filters are photolabile upon protracted UV exposure, leading to the formation of photoproducts of unknown toxicity for human health and environment. The chemical environment surrounding UV filters may strongly affect their behaviour: the interaction with other components of sunscreen formulations may enhance their degradation. Particularly, the interaction between photochemically incompatible ingredients must be avoided. Therefore, much effort has been invested in developing more effective and safe sunscreens.Our team recently focused on the preparation and characterization of hybrid UVfs obtained by the encapsulation of organic UV filters into various zeolites differing for topology. The zeolite most efficient for the encapsulation of organic UV filters, in term of stability and efficiency in radiation filtration, resulted to be LTL zeolite. Here, hybrid materials realized after the encapsulation of octinoxate (OMC) and avobenzone (AVO) in LTL zeolite were tested in terms of skin permeation profiles, cytotoxicity and photostability once the materials are dispersed in cream formulations, so to mimicking the real condition of use.The results show that the hybrids were successfully incorporated into oil-in-water emulsions and the skin permeation tests displayed a very low UV filter permeation through pig skin and no UV filter accumulation in dermis layer.The photostability of the hybrid-based emulsions were compared with that of emulsions containing a mixture of bare OMC and AVO, highlighting a reduced decrease in UV screening efficiency upon irradiation for the samples containing the hybrid materials with respect to the free filters. This evidence confirms that the encapsulation in the zeolite frameworks prevents some of the photodegradation reactions. The result of this paper highlights that zeolite encapsulation is increasingly establishing as a viable way to stabilize UV filters and other photoactive molecules.

Quality by Design Assisted Development of Luliconazole Transethosomes in Gel for the Management of Candida albicans Infection.

The objective of this study was to develop and evaluate a novel vesicular formulation of luliconazole (LUL) for the management of Candida albicans infection through a topical route. LUL-loaded transethosomes (LUL-TE) were prepared by the film hydration method and various independent and dependent variables were optimized using the Box-Behnken design. Selected critical material attributes were the content of phospholipids (X1), concentration of ethanol (X2), and amount of sodium cholate (X3). Formulated LUL-TE were characterized for percent entrapment efficiency, percent drug loading, vesicle size, and polydispersity index (PDI) and were incorporated into the carbomer gel base and further evaluated for gel characterizations. The prepared transethosomal gel (LUL-TE-CHG) was evaluated for pH, spreadability, viscosity, antifungal activity, and in vitro study. From the observed results, it was evident that the prepared LUL-TE-CHG was in the desired pH (6.2 ± 0.45), spreadability [8.3 ± 0.42 g/(cm·s)], viscosity (236.1-19.2.26 mPa·s), nanovesicle size (252 ± 9.82), entrapment efficiency (85% ± 5.24%), zeta potential (-34.05 ± 3.52 mV), and PDI (0.233 ± 0.002). The zone of inhibition results suggested that the LUL-TE-CHG formulation has the highest antifungal activity, that is, 5.83 ± 0.15 mm3. The in vitro results showed that drug release within 2 h was 18.1% ± 2.0% and after that sustained release action, 83.2% ± 1.7% within 8 h. Finally, to confirm the therapeutic efficacy of the developed formulation, fungal infection was induced by using C. albicans in Wistar rats. In vivo, skin irritation study and histopathology studies were performed in the disease-induced model. Animal experiments revealed that LUL-TE-CHG has significantly improved the diseased condition in Wistar rats. The results observed from the skin permeation and skin deposition profile ensure that the prepared novel LUL-loaded TE system had a higher permeation rate and increased retention time compared with LUL-CHG. The hydrogel incorporated with LUL could be a novel approach with safe and effective fungal treatment.

Bioinspired labrum-shaped stereolithography (SLA) assisted 3D printed hollow microneedles (HMNs) for effectual delivery of ceftriaxone sodium

Microneedles (MNs), a microsystem having needle height in micrometers, have gained significant attention due to their minimum invasiveness, painless, and easy-to-administer nature. Here, we introduce a hollow microneedle (HMNs) array with bio-inspired labrum tip for low insertion force and desired mechanical strength, fabricated using vat-photopolymerization mediated stereolithography (SLA) assisted 3D printing technology utilizing biocompatible photo-crosslinkable and curable resin as feedstock. Fabricated HMNs was used for the effective transdermal delivery of a broad-spectrum antibiotics i.e., ceftriaxone sodium (CEF) with a high molecular weight of 554.58 g mol−1, possessing gastro-intestinal (GI) instability and low oral bioavailability (BA). The bio-inspired labrum tip structure of the fabricated HMNs was evaluated by digital microscopy and scanning electron microscopy (SEM) to ensure the printed prototype's superiority in terms of dimensions and array uniformity. The HMN microchannels were then characterized by X-ray microcomputer tomography (µCT) to ascertain the quality of internal channels and ensure even distribution of drug solution. Further, HMNs was also characterized for mechanical and penetration analysis. Suggesting a low force of 1.54 N was required for its effective penetration with a sufficient fracture force of around 171.82 N. The ex vivo skin permeation profile of CEF from the HMNs revealed 100 ± 0.80 % CEF permeation through porcine skin within 18 hr. Finally, a pre-clinical efficacy assessment of CEF-reservoir HMNs was performed in an experimental animal model, revealing efficient penetrability and desired BA of CEF. Overall results demonstrated the active transdermal drug delivery potential of these fabricated bio-inspired HMNs as a unique device for customized and personalized treatment.

Saponin-based natural nanoemulsions as alpha-tocopherol delivery systems for dermal applications

Nanoemulsions can be produced using simple methods and compounds from natural sources. They can increase water dispersibility and bioavailability and optimise active ingredient dispersion in particular skin layers. Lipophilic compounds of the vitamin E family (tocopherols and tocotrienols) are well-known for their high antioxidant activity and capacity to protect the skin from oxidative stress. In this context, oil-in-water (o/w) nanoemulsions with and without α-tocopherol (Vitamin E, VE) were formulated with two emulsifier alternatives, Quillaja saponin (QS), and a combination of QS with Tribulus terrestris (QSTT) (50/50, w/w). The emulsions were evaluated concerning stability, microstructure, droplet size, colour attributes, encapsulation efficiency, UV photostability, antioxidant activity, and in vitro permeation studies to assess the delivery potential. Results showed highly stable systems, with round-shape droplets of 80–121 nm size. QS and QSTT samples' colours were close to white and light brownish, respectively. The topical nano cream had the capacity to entrap VE, producing a protective effect from UV degradation, and very significant antioxidant activity, with IC50 values around 0.01 %wt. The skin permeation profiles showed the efficiency of the formulations in the delivery of VE, with permeabilities between 64 and 74 µg/cm2, while the control sample showed no VE permeation.

Biodegradable Polymeric Pharmaceutical Nanoemulgel Coloaded with Eucalyptol‐Lornoxicam: Fabrication and Characterizations for Possible Better Pain Management

Nanoemulgels are considered as potential and ideal drug delivery systems for the transdermal administration of poorly soluble drugs like lornoxicam. Their intrinsic characteristics, such as small globule size as well as excipient type, make transdermal passage of the drug easier. The current study was aimed at developing nanoemulgel based formulation of lornoxicam coloaded with eucalyptol to enhance drug skin permeation and bioavailability in order to promote therapeutic outcome in appropriate time. High shear homogenization technique was utilized to develop optimized lornoxicam encapsulated nanoemulsion followed by its conversion into nanoemulgel formulation by the addition of 1% Carbopol 940 as gelling agent. Different characterization tests were performed on optimized formulation such as surface charge, particle size and size distribution, viscosity, spreadability, pH, drug content determination, drug entrapment efficiency, in vitro drug release, and drug permeation analysis. The optimized formulation had globule size of 143.7 ± 2.18 nm. The results of drug entrapment efficiency, in vitro drug release, and skin penetration experiments were found satisfactory. Based on the formulation type, permeability parameters such as permeability constant (Kp), enhancement ratio (Er), and steady state flux (Jss) revealed greater values and satisfactory outcomes. When compared to other formulations (LRX nanoemulgel and EU nanoemulgel), the LRX‐EU nanoemulgel formulation produced improved skin permeation profile (flux, 189.63 ± 7.68 μg/cm2/h; permeability coefficient, 2.09 ± 0.067 cm/h; and ER, 4.274). This work clearly proved that lornoxicam coloaded with eucalyptol nanoemulgel formulations could be developed to generate stable drug delivery systems. Thus, LRX‐EU NEG formulation seems promising in terms of physicochemical properties, enhanced bioavailability, and high skin penetration profile as compared to LRX NEG formulation.

Development and Evaluation of Nanostructured Lipid Carriers for Transdermal Delivery of Ketoprofen

Purpose: Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) which when administered via an oral route displays significant gastro-intestinal side effects and has low skin permeation profile. The objective of the present work is to utilise nanostructured lipid carriers (NLCs) as carrier system for transdermal delivery of ketoprofen. 
 Methods: NLCs were prepared via hot homogenisation technique using bees wax, carnauba wax, glycerl monostearate (solid lipids), linseed oil (liquid lipid) and poloxamer188 (surfactant) and optimized using custom design via JMP. The responses evaluated were drug entrapment efficiency, particle size and drug release profile. The experimental design was evaluated for model fit with the assistance of ANOVA. The optimum formulations were characterized for particle size, zeta potential, SEM, DSC, FTIR and also drug content, entrapment efficiency, in- vitro drug release, ex-vivo drug release profile was studied.
 Results: The drug entrapment in the range of 34±0.03-95.06±0.01%. The drug release from the formulations over a 24 h study was found to be 80%±0.09 to 95%±0.06. The maximum desirability was found to be 0.91. The optimum formulation showed mean particle size of 425.8nm and a zeta potential of -45mV. SEM results revealed slightly agglomerated particles with uneven surfaces. The ex-vivo skin permeation of NLC optimized patch formulation exhibited a higher flux and permeability coefficient in comparison to the pure drug patch formulation and marketed gel (2.5%w/w) FTIR spectra assured the chemical and physical compatibility. 
 Conclusion: Transdermal delivery of ketoprofen via NLCs would be a promising approach for improving the skin permeation.

Piper aduncum Essential Oil Rich in Dillapiole: Development of Hydrogel-Thickened Nanoemulsion and Nanostructured Lipid Carrier Intended for Skin Delivery.

The essential oil extracted from the leaves of Piper aduncum, an aromatic plant from the Amazon region, is rich in dillapiole and presents anti-inflammatory activity. In this study, nanoemulsions (NE) and nanostructured lipid carriers (NLC), which are biocompatible nanostructured systems of a lipid nature, were prepared by high-pressure homogenization for the yet unexplored skin delivery of dillapiole. The addition of hydroxyethylcellulose produced hydrogel-thickened NE or NLC in view to improving the viscosity and skin adherence of the nanoformulations. Formulations were characterized with respect to dillapiole content, droplet size, polydispersity index, zeta potential, morphology, rheological behavior, bioadhesion, skin permeation profile, and in vitro irritancy (HET-CAM). The formulations developed presented spherical, homogeneous nanometric particle size (around 130 nm), narrow polydispersity index (<0.3), and negative zeta potential (around -40 mV). Dillapiole content was slightly lower in NLC compared to NE since the production process involves heating. The hydrogels containing nanocarriers showed pseudoplastic behavior with bioadhesive characteristics. The developed formulations exhibited a controlled release profile, dillapiole delivery up to the dermis, the layer of interest for anti-inflammatory potential, and low irritant potential in the chorioallantoic membrane (HET-CAM). Both hydrogels-thickened NE and NLC seemed to be promising formulations for skin delivery of Piper aduncum essential oil.

Spotlight on Calcipotriol/Betamethasone Fixed-Dose Combination in Topical Formulations: Is There Still Room for Innovation?

Psoriasis is a lifelong disease which requires treatment adherence for successful management. Considering the complexity of this pathology, the combination of active pharmaceutical ingredients with a synergistic mechanism of action can improve the safety and efficacy of the treatment with respect to the conventional monotherapy. Moreover, a fixed dose of therapeutic agents in a topical formulation offers the possibility to simplify administration, reduce the doses of each active ingredient, and improve patient’s compliance. Among the first-line treatments in mild to moderate psoriasis, the formulation of calcipotriol (Cal) and betamethasone dipropionate (BD) in a single vehicle is challenging due to their chemical incompatibility in an aqueous environment and the formation of degradation products. Based on these considerations, this review aims to provide an overview on the biopharmaceutical properties of Cal/BD fixed-dose combination products available on the market (namely ointment, oleogel, foam, and O/W cream), highlighting also the novel approaches under evaluation. The main differences among topical formulations are discussed considering the different features of the anatomic districts involved in psoriasis and the patient’s adherence. Moreover, since in vitro experiments are fundamental to evaluate the skin permeation profile during the development of an efficacious medicinal product, special emphasis is given to models proposed to mimic psoriatic lesions.

Correlation between the Skin Permeation Profile of the Synthetic Sesquiterpene Compounds, Beta-Caryophyllene and Caryophyllene Oxide, and the Antiedematogenic Activity by Topical Application of Nanoemulgels.

Sesquiterpene compounds are applied as permeation promoters in topical formulations. However, studies exploring their impact on nanostructured systems, changes in permeation profile, and consequently, its biological activity are restricted. This study aimed to investigate the correlation between the skin permeation of the major sesquiterpenes, beta-caryophyllene, and caryophyllene oxide from the oleoresin of Copaifera multijuga, after delivery into topical nanoemulgels, and the in vivo antiedematogenic activity. First, ten nanoemulgels were prepared and characterized, and their in vitro permeation profile and in vivo anti-inflammatory activity were evaluated. In equivalent concentrations, β-caryophyllene permeation was greater from oleoresin nanoemulgels, resulting in greater in vivo antiedematogenic activity. However, an inverse relationship was observed for caryophyllene oxide, which showed its favored permeation and better in vivo anti-inflammatory effect carried as an isolated compound in the nanoemulgels. These results suggest that the presence of similar compounds may interfere with the permeation profile when comparing the profiles of the compounds alone or when presented in oleoresin. Furthermore, the correlation results between the permeation profile and in vivo antiedematogenic activity corroborate the establishment of beta-caryophyllene as an essential compound for this pharmacological activity of C. multijuga oleoresin.

Thermal analysis applied to the development of nanostructured lipid carriers loading propranolol using quality-by-design strategies

This work aimed to employ thermal analysis to develop nanostructured lipid carriers (NLC) using propranolol (PPL) as a model drug. The rationale for this is such delivery system could enable PPL repositioning for the treatment of skin diseases. For this, preformulation studies were first performed following a simplex centroid mixture design using thermal and spectroscopic analytical tools. Next, PPL-loaded NLC were developed, varying the production parameters according to a Box-Behnken design. A high degree of thermal interaction was observed among the formulation components, mainly between the Rosa rubiginosa essential oil and soy lecithin lipids, which resulted in an NLC entrapment efficiency above 98%. Infrared data, in turn, showed the components of the formulation are chemically compatible, even under heating production conditions. The optimized model for PPL-loaded NLC production allowed to accurately control the parameters of particle size and PdI on-demand over a wide range of particle sizes (400–1,500 nm). Particularly, Turrax rotation and Turrax agitation time were the most decisive process parameters for these responses. The optimized model was tested in the production of 500-nm and 900-nm NLC, leading to particle sizes of 569.4 ± 87.3 nm and 823.9 ± 58.0 nm, respectively, within the 95% confidence interval. Moreover, the PdI results were also very close to the prediction. In conclusion, the precise control of PPL-loaded NLC characteristics through the optimized model offers exciting perspectives for modulating the PPL skin permeation profile to meet different therapeutic propositions.

The Physicochemical, Biopharmaceutical, and In Vitro Efficacy Properties of Freeze-Dried Dexamethasone-Loaded Lipomers.

Dexamethasone-loaded polymer hybrid nanoparticles were developed as a potential tool to treat alopecia areata due to their follicular targeting ability. Freeze drying (FD) is a common technique used to improve nanoparticle stability; however, there are few studies focused on its effect on ethyl cellulose lipid-core nanoparticles. Nanoparticles were lyophilized with different cryoprotectants. Sucrose was selected because it allowed for a good resuspension and provided acceptable physicochemical parameters (374.33 nm, +34.7 mV, polydispersion 0.229%, and 98.87% encapsulation efficiency). The nanoparticles obtained were loaded into a pleasant xanthan gum hydrogel, and the rheological, release, and skin permeation profiles of different formulations were studied. The FD formulation significantly modified the particle size, and the drug release and permeation properties were also altered. In addition, analyses of the cytotoxicity and anti-inflammatory efficacy of FD and non-FD particles on human keratinocytes indicated no differences.

Nanostructured lipid carrier to overcome stratum corneum barrier for the delivery of agomelatine in rat brain; formula optimization, characterization and brain distribution study

The current work attempted to achieve bypassed hepatic metabolism, controlled release, and boosted brain distribution of agomelatine by loading in NLC and administering via transdermal route. Agomelatine-loaded NLC (AG-NLC) was fabricated employing melt-emulsification technique and optimized using central composite design. The optimized AG-NLC had 183.16 ± 6.82 nm particle size, 0.241 ± 0.0236 polydispersity index, and 83.29 ± 2.76% entrapment efficiency. TEM and FESEM visually confirmed the size and surface morphology of AG-NLC, respectively. DSC thermogram confirmed the conversion of AG from crystalline to amorphous form, which indicates improved solubility of AG when loaded in NLC. For further stability and improved applicability, AG-NLC was converted into a hydrogel. The texture analysis of AG-NLC-Gel showed appropriate gelling property in terms of hardness (142.292 g), cohesiveness (0.955), and adhesiveness (216.55 g.sec). In comparison to AG-suspension-Gel (38.036 ± 6.058%), AG-NLC-Gel (89.440 ± 2.586%) exhibited significantly higher (P < 0.005) skin permeation profile during the 24 h study. In the CLSM study, Rhodamine-B loaded AG-NLC-Gel established skin penetration up to the depth of 45 µm, whereas AG-Suspension-Gel was restricted only to a depth of 25 µm. γ-scintigraphy in wistar rats revealed ~ 55.38% brain distribution potential of 99mTc-AG-NLC-Gel at 12 h, which was 6.31-fold higher than 99mTc-AG-Suspension-Gel. Overall, the gamma scintigraphy assisted brain distribution study suggests that NLC-Gel system may improve the brain delivery of agomelatine, when applied transdermally.

Biorelevant In Vitro Skin Permeation Testing and In Vivo Pharmacokinetic Characterization of Lidocaine from a Nonaqueous Drug-in-Matrix Topical System

Recently, lidocaine topical systems utilizing nonaqueous matrices have been developed and provide efficient lidocaine delivery through the skin, such that lower concentrations of drug provide equivalent or greater drug delivery than drug-in-matrix hydrogel lidocaine patches. This study characterizes drug delivery from a nonaqueous lidocaine topical system with increasing drug load both in vitro and in vivo. Topical systems formulated with either 1.8% or 5.4% lidocaine were applied to healthy volunteers’ backs (n = 15) for 12 h in a single-center, open-label, four-treatment, four-period crossover pharmacokinetic study. Subjects were dosed with either three 1.8% systems or one, two, or three 5.4% systems in each period. Blood was collected for up to 48 h, and plasma lidocaine levels were measured with a validated HPLC method. In parallel, human and mouse skin models characterized the in vitro skin permeation profile. The pharmacokinetic profile was linear between one, two, and three lidocaine 5.4% applications. Application of three lidocaine 1.8% systems (108 mg lidocaine) was bioequivalent to one lidocaine 5.4% system (108 mg lidocaine). Both topical systems remained well adhered to the skin and irritation was mild. The 5.4% system had approximately threefold higher skin permeability than the 1.8% system in the mouse and human skin models. The results indicate increasing the drug load by three times results in triple the drug delivery both in vivo and in vitro. The relationship between the in vitro permeation and in vivo absorption correlates and is nonlinear.

Influence of Lactobacillus Biosurfactants on Skin Permeation of Hydrocortisone.

One of the most widely used strategies to improve drug diffusion through the skin is the use of permeation enhancers. The aim of this work was to investigate the effect of two biosurfactants (BS), produced by Lactobacillus crispatus BC1 and Lactobacillus gasseri BC9, on the skin permeation profile of hydrocortisone (HC, model drug). HC aqueous solubility and in vitro diffusion studies through porcine skin were performed in the presence of BC1-BS and BC9-BS at concentrations below and above critical micellar concentrations (CMC). Moreover, skin hydration tests and differential scanning calorimetry (DSC) analysis were performed to further investigate BS interaction with the outermost layer of the skin. Both BS increased HC solubility, especially at concentrations above their CMC. At concentrations below the CMC, drug permeation through the skin was improved, as the result of a dual effect: a) the formation of a superficial lipophilic environment, as confirmed by the reduction in skin hydration and b) the interaction between BS and the stratum corneum (SC), as demonstrated by the DSC curves. From the obtained data, it appears that BC1-BS and BC9-BS could represent new promising green excipients for drug permeation enhancement through the skin.

An investigation on percutaneous permeation of flurbiprofen enantiomers: The role of molecular interaction between drug and skin components

This work aimed to investigate skin permeation profiles of chiral flurbiprofen and clarify the molecular mechanism of transdermal permeation difference of enantiomers. The in vitro transdermal permeation of enantiomers through rat skin was studied by diffusion cells. Physicochemical parameters of model chiral drugs were determined. Molecular interaction between chiral flurbiprofen and ceramides of skin was investigated by FTIR, 13C NMR and molecular docking. The skin permeation mechanism of chiral drugs was characterized by ATR-FTIR, Raman spectra, DSC and molecular dynamic simulation. The results showed that the amount of the permeation and retention amount of (S)-flurbiprofen was 1.5 times over that of (R)-flurbiprofen. And it was proven that the difference was not induced by physicochemical properties but the molecular interaction between drug-skin components. (S)-flurbiprofen was easy to form stronger hydrogen bonding with –CONH group of skin lipids due to its steric configuration, which disturbed lipids arrangement more easily according to the results of ATR-FTIR (ΔνasCH2 = 1.00 cm−1), Raman spectra (ΔI2882/I2853 = 0.32) and the DSC (ΔTm stratum corneum = 11.75 °C). It was demonstrated more obvious effect on the second structure of keratin by ATR-FTIR study (Δ Amide I = 3.60 cm−1 and Δ Amide II = 3.38 cm−1). Better compatibility between (S)-flurbiprofen and lipids was confirmed quantificationally by thermodynamic analysis. In conclusion, the higher interaction between (S)-flurbiprofen and skin components, the higher skin permeation, which contributes to decrease the administration dose and increase the therapeutic effect.

Development and validation of LC-MS/MS method for the determination of UV-filters across human skin in vitro

A novel High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) method was developed for the simultaneous determination of the in vitro skin permeation profile of four UV filters. The sunscreen products contained the following components: octocrylene (OC), ethylhexyl methoxycinnamate (EHMC), diethylamino hydroxybenzoyl hexyl benzonate (DHHB) and ethylhexyl salicylate (EHS). The target compounds were analyzed by HPLC-MS/MS method in positive ionization electrospray (ESI) in Multiple Reaction Monitoring (MRM) mode. The proposed method was validated in terms of the detection (LOD) and quantification limits (LOQ), linearity range, intra- and inter- day precision and accuracy of the analysis. The stability of the target compounds in solutions was also studied. All tests provided satisfactory results illustrating acceptable method performance. Samples were analyzed with simple pretreatment procedure, necessary to achieve solvent change and preconcentration. To evaluate matrix effect, the slopes of the standard regression curves with those of the matrix-matched calibration curves were compared using the Student’s t-test. Quantitative evaluation of the test samples was performed using external methanolic calibration curves. Accuracy was found within the range 94.37–108.76%. The method was successfully applied to the analysis of UV filters in samples after permeability studies, in Franz's cells, for 24 h, using human skin. Concentration of sunscreens in the acceptor phase at the timescale of 24 h was very low implying the safety of the products.

Transfersomes- a Novel Vesicular Carrier for Enhanced Transdermal Delivery of Stavudine: Development, Characterization and Performance Evaluation

The aim of the present study was to investigate the potential of transfersomal formulations for transdermal delivery of Stavudine and to evaluate Span 80, Tween 80, Sodium cholate and Sodium deoxycholate as edge activators. Vesicles containing phosphatidylcholine (PC) mixed with edge activators and Stavudine were prepared by conventional rotary evaporation method and characterized by various parameters (vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity and in vitro drug release). The compositions of refined formulations were predicted, liposomes prepared and tested against control. Skin permeation profile of transfersomal formulation bearing Stavudine was observed and the investigations revealed an enhanced transdermal flux (8.91±0.9 μg/cm2/hr) and decrease lag time (0.9 hr) for Stavudine. The obtained flux was nearly 7.5 and 12.04 times higher than conventional liposomal formulation bearing Stavudine and plain drug solution. These results suggested that transfersomes are potential vehicles for improved transdermal delivery of Stavudine and Span 80, Tween 80 and Sodium cholate were equivalent to Sodium deoxycholate as edge-activators.