Percutaneous Absorption Studies Research Articles

In vitro percutaneous absorption studies of cannabidiol using human skin: Exploring the effect of drug concentration, chemical enhancers, and essential oils

Cannabidiol, a non-psychoactive constituent of cannabis, has garnered much attention after United States Food and Drug Administration approved Epidiolex® for oral use. Although therapeutic effect of cannabidiol after systemic absorption has been investigated extensively, its therapeutic potential in treating skin disorders after local delivery still needs further exploration. Our study has investigated the effect of cannabidiol concentration, chemical enhancers, and essential oils on percutaneous absorption of cannabidiol. In vitro permeation tests were conducted on human skin. The 24 h study results suggest no significant difference in amount of drug absorbed into skin, between 5% (242.41 ± 12.17 µg/cm2) and 10% (232.79 ± 20.82 cm2) cannabidiol solutions. However, 1% delivered (23.02 ± 4.74 µg/cm2) significantly lower amount of drug into skin than 5% and 10%. Transcutol and isopropyl myristate did not enhance delivery of cannabidiol. However, oleic acid was found to be useful as chemical enhancer. Oleic acid (43.07 ± 10.11 µg/cm2) had significantly higher cannabidiol delivery into skin than the group without oleic acid (10.98 ± 3.40 µg/cm2) after a 4 h in vitro permeation study. Essential oils at concentrations tested had lower total cannabidiol delivery when compared to control. This study's findings will help guide future research on the pharmacological effect of percutaneously delivered cannabidiol on inflammatory skin disorders.

Graphite flame retardant applied on polyester textiles: flammable, thermal and in vitro toxicological analysis

Expandable graphite was applied to an upholstery polyester textile material as an eco-friendly flame-retardant alternative to halogenated compounds. Fabrics treated with the flame retardant were evaluated by flammability tests. Besides, thermal analysis was carried out by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Moreover, a percutaneous absorption study was conducted to verify the safety in terms of dermal penetration of the flame-retardant treated upholstery fabric for human use. The upholstery fabric treated with expandable graphite successfully passed the flammability tests. Thermogravimetric analyses with TGA and DSC showed that the flame-retardant application slightly decreased the initial decomposition temperatures regardless of the atmosphere but increased the final residue at 600°C (35.7% in O2 and 44.5% in N2) compared to non-treated upholstered fabrics. Dermal permeation of expandable graphite applied on the polyester fabric showed no penetration after 24 h of fabric exposure time. This result demonstrated that graphite-treated polyester fabric is dermatologically and toxicologically safe for use in upholstery. Applied expandable graphite proved an efficient and safe flame-retardant alternative to conventional flame retardants for eco-friendly flame resistance applications in upholstery fabrics.

Lanolin-Based Synthetic Membranes for Transdermal Permeation and Penetration Drug Delivery Assays.

Due to the high similarity in composition and structure between lanolin and human SC lipids, we will work with two models from wool wax. Two types of lanolin were evaluated: one extracted with water and surfactants (WEL) and the other extracted with organic solvents (SEL). Skin permeation and skin penetration studies were performed with two active compounds to study the feasibility of the use of lanolin-based synthetic membranes as models of mammalian skin. Diclofenac sodium and lidocaine were selected as the active compounds considering that they have different chemical natures and different lipophilicities. In the permeation assay with SEL, a better correlation was obtained with the less permeable compound diclofenac sodium. This assay suggests the feasibility of using artificial membranes with SEL as a model for percutaneous absorption studies, even though the lipophilic barrier should be improved. Penetration profiles of the APIs through the SEL and WEL membranes indicated that the two membranes diminish penetration and can be considered good membrane surrogates for skin permeability studies. However, the WEL membranes, with a pH value similar to that of the skin surface, promoted a higher degree of diminution of the permeability of the two drugs, similar to those found for the skin.

Evaluation of porcine skin layers separation methods, freezing storage and anatomical site in in vitro percutaneous absorption studies using penciclovir formulations

Literature reveals high variation in the techniques used for in vitro studies of percutaneous absorption, resulting in several outcomes and making it difficult to establish a correlation with in vivo absorption. This paper investigates the role of the main parameters that may influence on the penetration/permeation profile of penciclovir as a model drug, from a conventional (cream) and an innovative formulation (hydrogel nanoemulsion) in porcine skin. The parameters evaluated were: the separation method of skin layers after contact with formulation, the penetration and permeation skin capacity according to frozen storage time (up to three months of storage) and the evaluation of different anatomical sites (abdomen and ear). Concerning the separation method of skin layers, this study showed that, for both products, there was a drug loss when the hot water immersion classic technique was employed. Regardless of the anatomical site, there was no significant difference for the penetration and permeation for both formulations between the non-scalded abdomen and ear skin. Finally, it was confirmed that porcine skin permeability does not vary significantly with frozen storage for up to 30 days. Our findings provide new understandings about the parameters addressed and will further stimulate their application as an important knowledge for in vitro percutaneous studies.

Development of nanoemulsions containing penciclovir for herpes simplex treatment and a liquid chromatographic method to drug assessment in porcine skin layers

A successful formulation (penciclovir hydrogel nanoemulsion - HN) to be used in transdermal drug delivery route to treat herpes simplex virus was developed and an analytical method to quantify penciclovir (PCV) in porcine ear skin was stablished and validated. PCV nanoemulsions were prepared by high pressure homogenization and presented spherical mean droplet size 180 nm. The association efficiency and zeta potential were 87% and– 27 mV, respectively. The bioanalytical method developed showed specificity for the interferences from the skin matrixes (epidermis and dermis) and the linearity was in the range 0.1 – 25 μg/mL of drug, The mean recovery data for the three levels tested were 95.2% for the epidermis and 97.3% for the dermis and adequate results were obtained for repeatability and inter-day precision. In vitro percutaneous absorption studies with the PCV nanoemulsion and a market cream were conducted employing the porcine skin.The cumulative amounts of PCV permeated from cream and HN, 8 h after dosing, were 2.60 and 4.15 μg/cm², respectively, representing a quite higher flux and a much higher permeability coefficient for the developed formulation. It can be concluded that HN provide a good skin targeting effect and may be a promising carrier for topical delivery of penciclovir.

Development of Poly (Methyl vinyl ether-alt-maleic acid) Microneedles for Transdermal Delivery of Atorvastatin Calcium.

Biodegradable polymeric microneedles containing atorvastatin calcium were developed in order to improve the percutaneous absorption of the drug, useful for the treatment of hypercholesterolemia. The use of physical enhancers like microneedles have shown good results to increase the delivery of drugs through the skin, the use of microneedles has very important advantages for transdermal drug delivery, for example, they are painless, easy to use and safe, they increase time interval of drug activity, dose, and reductions in adverse reactions, they also offer, the facility to remove the system instantly of the skin. Develop polymer microneedles loaded with a calcium atorvastatin and evaluate them by Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), bioadhesion, postwetting- bioadhesion, breaking strength, drug release test and in vitro percutaneous absorption studies to demonstrate the use of microneedles atorvastatin is able to cross the skin. The microneedles were made with poly (methyl vinyl ether-alt-maleic acid) as biodegradable polymer using the technique of casting in solution in a mold. After solidification these microneedles were characterized by Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), bioadhesion, post-wetting-bioadhesion, breaking strength, drug release test and in vitro percutaneous absorption studies. In general, the performances were satisfactory for optimal formulation in terms of DSC with no interactions between drug and excipients, SEM shows microneedles with a conical shape, bioadhesion of 1570 g.f, post wetting-bioadhesion of 1503.4 g.f, breaking strength of 1566.7g.f that is sufficient to disrupt Stratum corneum, good drug release and a flux of 33.4 μg/cm2*h with a tLag of 15.14 h for the in vitro percutaneous absorption. The results indicate that it is possible to generate microneedles to increase the percutaneous absorption of calcium atorvastatin transdermally, with the potential to be used as an alternative to the oral route for the treatment of dyslipidemias.

Use of Nanomaterial-Based (Micro)Extraction Techniques for the Determination of Cosmetic-Related Compounds.

The high consumer demand for cosmetic products has caused the authorities and the industry to require rigorous analytical controls to assure their safety and efficacy. Thus, the determination of prohibited compounds that could be present at trace level due to unintended causes is increasingly important. Furthermore, some cosmetic ingredients can be percutaneously absorbed, further metabolized and eventually excreted or bioaccumulated. Either the parent compound and/or their metabolites can cause adverse health effects even at trace level. Moreover, due to the increasing use of cosmetics, some of their ingredients have reached the environment, where they are accumulated causing harmful effects in the flora and fauna at trace levels. To this regard, the development of sensitive analytical methods to determine these cosmetic-related compounds either for cosmetic control, for percutaneous absorption studies or for environmental surveillance monitoring is of high interest. In this sense, (micro)extraction techniques based on nanomaterials as extraction phase have attracted attention during the last years, since they allow to reach the desired selectivity. The aim of this review is to provide a compilation of those nanomaterial-based (micro)extraction techniques for the determination of cosmetic-related compounds in cosmetic, biological and/or environmental samples spanning from the first attempt in 2010 to the present.

Ultrasound-mediated topical delivery of econazole nitrate with potential for treating Raynaud's phenomenon.

The study aims to assess the ultrasound-assisted econazole nitrate (EN) permeation from topically applied formulations with potential for treating Raynaud's phenomenon. Optimization of ultrasound parameters such as the distance of the horn, application time and amplitude were performed. In vitro percutaneous absorption studies were performed using econazole formulations (F2_HPMC dispersion, F4_Lipoderm® Activemax™ Cream) across the ultrasound-treated porcine skin and were compared with the control group (skin samples without ultrasound). Histology and ATR-FTIR studies were performed on treated skin samples. A constant frequency (20kHz) ultrasound application with 40% amplitude, 0.5cm distance between ultrasound horn and the skin surface for 2min was optimized. The permeation of EN was found to be higher from ultrasound-treated skin samples than the control group. Drug permeation from F2_HPMC dispersion was found to be higher as compared to the other formulations and the marketed EN cream. Histological evaluation confirmed that F2_HPMC dispersion showed no signs of toxicity. ATR-FTIR studies revealed a slight increase in the CH2 stretching vibrations (~2920cm-1 and 2850cm-1) in ultrasound-treated skin samples as compared with the control. In conclusion, the ultrasound-assisted transdermal delivery of F2_HPMC dispersion could be further studied as a new therapy for Raynaud's phenomenon.

Polyvinylpyrrolidone microneedles for localized delivery of sinomenine hydrochloride: preparation, release behavior of in vitro & in vivo, and penetration mechanism

Sinomenine (SIN) is an anti-inflammatory alkaloid derived from Sinomenium acutum, and the products sinomenine hydrochloride (SH) tablets and injections have been marketed in China to treat rheumatoid arthritis (RA). Oral administration of SH has shortcomings of gastrointestinal irritation and low bioavailability. The injection may require professional training and higher cost. It is of interest to develop an alternative form that is easier to administer and avoids the first-pass metabolism. In this study, SH-loaded dissolving microneedles (SH-MN) were fabricated using polyvinyl pyrrolidone and chondroitin sulfate with a casting method. In percutaneous permeation studies of In vitro, the cumulative permeation and permeation rate of SH-MN were 5.31 and 5.06 times higher than that of SH-gel (SH-G). In percutaneous pharmacokinetic studies, the values of the area under the curve after administration of SH-MN in the skin and blood were 1.43- and 1.63-fold higher than that of SH-G, respectively. In percutaneous absorption studies, SH-MN could absorb into tissue fluid; and dissolve after skin penetration. The drug was released along the channel and spread to surrounding skin tissue. After 4 h, the needle tip was almost completely dissolved, and the drug could penetrate to a depth of 200 μm under the skin. These results demonstrate that the SH-MN is an effective, safe, and simple strategy for transdermal SH delivery.

Pravastatin Transdermal Patches: Effect of The Formulation and Two Different Lengths of Microneedles on In-vitro Percutaneous Absorption Studies.

Transdermal patches loaded with pravastatin was previously characterized in another published study by Serrano-Castañeda et al; 2015. These transdermal patches (TP) were generated by the plate casting technique, the in-vitro percutaneous absorption studies of TP were evaluated for three different formulations with different quantities of Pluronic F-127 (PF-127): i) without PF-127 (TP W), ii) 1% of PF-127 (TP 1%), and iii) 3% of PF-127 (TP 3%) using solid microneedles as a penetration enhancer with two different lengths: i) 0.25 mm and ii) 2.25 mm and iii) in-vitro permeation studies by passive diffusion. The fluxes (F), time lag (tLag) and permeability constants (Kp) for each formulation were: TP W (F:38.5µg/cm2*h, tLag:18.97h and Kp:5.9x10-3 cm/h), TP W with microneedles of 0.25 mm (F:103.3 µg/cm2*h, tLag: 20.76 h and Kp: 0.0158 cm/h), TP W and microneedles of 2.25 mm (F:105.2µg/cm2*h, tLag: 21.16 h and Kp: 0.0159cm/h), TP 1% (F:90 µg/cm2*h, tLag: 19.48 h and Kp: 0.0137 cm/h), TP 1% with microneedles of 0.25 mm (F:111.4µg/cm2*h, tLag:19.11h and Kp:0.017cm/h), and TP 1% with microneedles of 2.25 mm (F:115.2µg/cm2*h, tLag:16.73h and Kp:0.017cm/h), TP 3% (F:40.9µg/cm2*h, tLag:20.45h and Kp:0.0062 cm/h), TP 3% with microneedles of 0.25 mm (F:67.1 µg/cm2*h, tLag: 21.79h and Kp:0.0102cm/h) and TP 3% with microneedles of 2.25 (F:70.5 µg/cm2*h, tLag:20.44h and Kp:0.0107cm/h). Results show that the formulation of TP affects the pravastatina flux and Kp parameters, however the length of microneedles only has important effect on tLag.

Modulation of the Lipid Profile of Reconstructed Skin Substitutes after Essential Fatty Acid Supplementation Affects Testosterone Permeability.

Skin models with efficient skin barrier function are required for percutaneous absorption studies. The contribution of media supplementation with n-3 and n-6 polyunsaturated fatty acids (PUFAs) to the development of the skin barrier function of in vitro skin models remains incompletely understood. To investigate whether PUFAs, alpha-linolenic acid (ALA, n-3 PUFA) and linoleic acid (LA, n-6 PUFA), could enhance the impermeability of a three-dimensional reconstructed human skin model, skin substitutes were produced according to the self-assembly method using culture media supplemented with either 10 μM ALA or 10 μM LA. The impact of PUFAs on skin permeability was studied by using a Franz cell diffusion system to assess the percutaneous absorption of testosterone and benzoic acid. Our findings showed that ALA supplementation induced a decrease in the absorption of testosterone, while LA supplementation did not significantly influence the penetration of testosterone and benzoic acid under present experimental conditions. Both ALA and LA were incorporated into phospholipids of the skin substitutes, resulting in an increase in n-3 total PUFAs or n-6 total PUFAs. Collectively, these results revealed the under-estimated impact of n-3 PUFA supplementation as well as the importance of the n-6 to n-3 ratio on the formation of the skin barrier of in vitro reconstructed human skin models.

Time constant for the dermal absorption of semivolatile organic compounds from the gas phase of indoor air

A Laplace transform-based technique was applied to solve a mechanistic model and simulate scenarios often encountered in the percutaneous absorption studies of semivolatile organic compounds (SVOCs) from indoor air. The system included the stratum corneum layer, a skin surface lipid region and the viable epidermis. The new framework made it possible to provide analytical expressions for the effective time constant (teff). This dynamic key performance indicator helped estimate the time required to reach either a steady-state absorption rate or the total amount of SVOC absorbed into the bloodstream. In the case of a constant concentration Cg of the chemical, the flux reached 98.1% of its steady-state value at 4teff. When participants were exposed to 29.4 µg/cm3 of m-xylene vapors during an 8-hour period and zero concentration thereafter, the mass of m-xylene entering the bloodstream and the time constant were 4.40 mg and 1.02 h, respectively. The mass transfer coefficient between the air and the surface of the lipid layer (hm) remained unchanged. The methodology calculated teff in cases of varying hm and temporary Cg when an SVOC was absorbed into the capillaries after a relatively short exposure time.

Transdermal Oxandrolone: Ex Vivo Percutaneous Absorption Study.

Oxandrolone is a potent synthetic testosterone analogue that possesses strong anabolic property and weak androgenic activity. Apart of their clinical implicances, oral oxandrolone can potentially promote several adverse effects. It is known that the transdermal delivery of drugs may represent a means to avoid or minimize oral adverse effects Thus, the objective of this study was to evaluate the permeability of oxandrolone in human skin on a preliminary basis for possible future determination of the transdermal route as an alternative to oral treatments. We used a percutaneous absorption assay in Franz diffusion cells coupled with freshly excised human skin. The drug release kinetics were determined to predict the efficiency of this alternative route for the drug. Nearly 236 μg (86.7%, in terms of applied dose) of the product was prevented to permeate due to the barrier function of the stratum corneum (SC); 21.6% reached the receptor medium (RM), and the remaining 4.3% were quantified within viable layers of the skin (in vivo, dermis is vascularized). The total amount of drug able to exert effect is the sum of the drug quantified within remained skin (RS) and RM: then, a total of 247.6 μg of oxandrolone (25.9% of the applied dose) would be able to permeate through a non damaged skin. The accuracy of the data is demonstrated by the calculated mass balance (average recovery = 112.6%). Transdermal oxandrolone could be a viable alternative for traditional oral form, once clinical studies are conducted to prove this hypothesis.

Inter-laboratory skin distribution study of 4-n-butyl resorcinol: The importance of liquid chromatography/mass spectrometry (HPLC-MS/MS) bioanalytical validation.

In the present study, three laboratories independently compared percutaneous absorption and distribution of 4-n-butylresorcinol, using human skin from five donors. Each laboratory used the same protocol for percutaneous absorption studies but different LC-MS/MS analytical methods to quantify the test compound. All laboratories respected the mass balance criteria (i.e. 100±15%; average 96.5-102% of applied dose). Regarding usual inter-lab variability, good agreement was observed for all compartments with the greatest difference in the epidermis: 3.3 fold increase. The data obtained demonstrate that robustness of skin absorption data rely on properly validated analytical methods including sample extraction and LC-MS/MS method. It also includes clearly defined cutaneous absorption protocol for dose skin preparation, application, washing and tape stripping.

Dendrimer pre-treatment enhances the skin permeation of chlorhexidine digluconate: Characterisation by in vitro percutaneous absorption studies and Time-of-Flight Secondary Ion Mass Spectrometry

Skin penetration and localisation of chlorhexidine digluconate (CHG) within the skin have been investigated in order to better understand and optimise the delivery using a nano polymeric delivery system of this topically-applied antimicrobial drug. Franz-type diffusion cell studies using in vitro porcine skin and tape stripping procedures were coupled with Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) to visualise the skin during various treatments with CHG and polyamidoamine dendrimers (PAMAM). Pre-treatment of the skin with PAMAM dendrimers significantly increased the amount and depth of permeation of CHG into the skin in vitro. The effect observed was not concentration dependant in the range 0.5–10mM PAMAM. This could be important in terms of the efficiency of treatment of bacterial infection in the skin. It appears that the mechanism of enhancement is due to the PAMAM dendrimer disrupting skin barrier lipid conformation or by occluding the skin surface. Franz-type diffusion cell experiments are complimented by the detailed visualisation offered by the semi-quantitative ToF-SIMS method which provides excellent benefits in terms of sensitivity and fragment ion specificity. This allows a more accurate depth profile of chlorhexidine permeation within the skin to be obtained and potentially affords the opportunity to map the co-localisation of permeants with skin structures, thus providing a greater ability to characterise skin absorption and to understand the mechanism of permeation, providing opportunities for new and more effective therapies.

Evaluation of the in vitro Human Skin Percutaneous Absorption of Progesterone in Versabase® Using the Franz Skin Finite Dose Model

Women may benefit from hormone replacement therapy to alleviate undesirable menopausal symptoms such as hot flashes, disruption of sleep and fatigue. Transdermal hormone replacement therapy consists in the delivery of hormones through the skin and into the blood stream, avoiding gastrointestinal drug absorption difficulties and the first pass effect. Transdermal compounded medications may be customized to meet the individual needs of women by changing the hormones used, the respective concentrations and the medicine’s formulation. Two compounded medications were prepared for progesterone 50 mg/g, as follows: Progesterone in VersaBase® Cream and progesterone in VersaBase® Cream Gel. The purpose of this study is to determine the in vitro human skin percutaneous absorption of progesterone for both test formulations. The Franz Skin Finite Dose Model was the methodology used to evaluate the total absorption, the rate of absorption and the skin content of progesterone applied to the outer surface of ex vivo skin. This model has proven to be a valuable tool for the study of percutaneous absorption of topically applied drugs and to accurately predict in vivo permeation kinetics. The skin samples were obtained within 24 h to 48 h of death from three adult Caucasian donors and a total of 17 Franz diffusion chambers were prepared for testing. Results are presented as the mean ± standard error per parameter, for each test formulation. The rate of percutaneous absorption, presented as mean flux, was similar for the two test formulations and characterized by 2 peaks at approximately 6 hours and 28 hours after dose application, followed by a decline in flux over time. The total absorption and the skin content of progesterone were also similar: 21.6% and 21.8% of the applied doses for the test formulations 1 and 2, respectively. Although in vitro, these results suggest that progesterone in VersaBase® is likely to be delivered through the skin and into the general circulation for systemic effects. Practitioners may then consider transdermal progesterone as a viable route of drug administration for menopausal women.

Evaluation of pharmacokinetics and in vitro/in vivo correlation of ibuprofen with essential oils as penetration enhancer following transdermal administration

The study was carried out to investigate the pharmacokinetics and in vitro/in vivo correlation of ibuprofen with essential oils as penetration enhancers (PE) following transdermal administration. With Azone as the positive control, ibuprofen hydrogels containing Chuanxiong oil, Angelica oil or Cinnamon oil as PE were prepared and administered to the rat abdominal skin. Then the pharmacokinetics of ibuprofen following transdermal administration were investigated and compared. In comparison with negative control (no PE was added), the relative bioavailability values with the addition of Chuanxiong oil, Angelica oil, Cinnamon oil and Azone as PE were determined to be 161.87%, 171.05%, 151.37% and 148.66%, respectively. In vitro/in vivo correlation analysis was performed by deconvolution method and the results demonstrated a good correlation between in vitro and in vivo percutaneous absorption studies. The correlation coefficients were measured to be 0.999 7, 0.995 2 and 0.999 4 for Chuanxiong oil, Angelica oil and Cinnamon oil respectively. In summary, Chuanxiong oil, Angelica oil and Cinnamon oil as PE could significantly enhance the bioavailability of ibuprofen following transdermal administration. A satisfactory in vitro/in vivo correlation could be obtained by using hydrogel as the dosage form.

Fixed-Combination Gels of Adapalene and Benzoyl Peroxide Provide Optimal Percutaneous Absorption Compared to Monad Formulations of These Compounds: Results from Two In Vitro Studies.

IntroductionAdapalene 0.1%/benzoyl peroxide 2.5% (0.1% A/BPO) and adapalene 0.3%/BPO 2.5% (0.3% A/BPO) gels are fixed-combination options for the topical treatment of acne. However, the active compounds of these combinations are also available as monads, to be used in association or as monotherapy. These two in vitro studies determined the effect of different treatment regimens on the percutaneous absorption of adapalene (0.1% and 0.3%) gels and BPO 2.5% gel in ex vivo human skin.MethodsIn vitro percutaneous absorption studies were conducted using full-thickness human skin from six donors. Treatment regimens included the application of 0.1% A/BPO, 0.3% A/BPO, or four free-combination regimens of the monads. Skin samples were incubated for 24 h. Concentrations of adapalene and BPO equivalent (BPO-eq) (i.e. benzoic acid after chemical transformation of BPO) were measured using high-performance liquid chromatography. Comparison of regimens was performed using a bioequivalence criterion (estimated ratio bewteen 0.8 and 1.25).ResultsThe fixed combination 0.3% A/BPO regimen demonstrated more than three times higher absorption of adapalene versus the fixed-combination 0.1% A/BPO. Based on the bioequivalence acceptance criterion, all four free-combination regimens were different from 0.1% A/BPO and 0.3% A/BPO, with higher adapalene release delivered by the fixed combinations versus the free combinations. For BPO-eq, the results showed that the free-combination regimens where adapalene 0.1% was applied first were different from 0.1% A/BPO, with lower BPO-eq release delivered by these regimens compared to the fixed combination. The regimen adapalene 0.3% for 10 h followed by BPO 2.5% delivered lower BPO-eq release compared to the fixed combination.ConclusionThe fixed-combination A/BPO gels provide optimal percutaneous absorption of the active compounds compared to free combinations of adapalene 0.1%, adapalene 0.3%, and BPO 2.5%. The higher concentration of adapalene in the 0.3% A/BPO gel and the resulting higher absorption may explain higher clinical efficacy.

Nanostructured Lipid Carriers (NLC) as Vehicles for Topical Administration of Sesamol: In Vitro Percutaneous Absorption Study and Evaluation of Antioxidant Activity.

Sesamol is a natural phenolic compound extracted from Sesamum indicum seed oil. Sesamol is endowed with several beneficial effects, but its use as a topical agent is strongly compromised by unfavorable chemical-physical properties. Therefore, to improve its characteristics, the aim of the present work was the formulation of nanostructured lipid carriers as drug delivery systems for topical administration of sesamol.Two different nanostructured lipid carrier systems have been produced based on the same solid lipid (Compritol® 888 ATO) but in a mixture with two different kinds of oil phase such as Miglyol® 812 (nanostructured lipid carrier-M) and sesame oil (nanostructured lipid carrier-PLUS). Morphology and dimensional distribution of nanostructured lipid carriers have been characterized by differential scanning calorimetry and photon correlation spectroscopy, respectively. The release pattern of sesamol from nanostructured lipid carriers was evaluated in vitro determining drug percutaneous absorption through excised human skin. Furthermore, an oxygen radical absorbance capacity assay was used to determine their antioxidant activity.From the results obtained, the method used to formulate nanostructured lipid carriers led to a homogeneous dispersion of particles in a nanometric range. Sesamol has been encapsulated efficiently in both nanostructured lipid carriers, with higher encapsulation efficiency values (> 90 %) when sesame oil was used as the oil phase (nanostructured lipid carrier-PLUS). In vitro evidences show that nanostructured lipid carrier dispersions were able to control the rate of sesamol diffusion through the skin, with respect to the reference formulations.Furthermore, the oxygen radical absorbance capacity assay pointed out an interesting and prolonged antioxidant activity of sesamol, especially when vehiculated by nanostructured lipid carrier-PLUS.

Econazole imprinted textiles with antifungal activity

In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining drug activity. Lipid microparticles were prepared and characterized by laser diffraction (3.5±0.1μm). Using an optimized screen-printing method, microparticles were deposited on textiles, as observed by scanning electron microscopy. The drug content of textiles (97±3μg/cm2) was reproducible and stable up to 4months storage at 25°C/65% Relative Humidity. Imprinted textiles exhibited a thermosensitive behavior, as witnessed by a fusion temperature of 34.8°C, which enabled a larger drug release at 32°C (temperature of the skin) than at room temperature. In vitro antifungal activity of ECN textiles was compared to commercial 1% (wt/wt) ECN cream Pevaryl®. ECN textiles maintained their antifungal activity against a broad range of Candida species as well as major dermatophyte species. In vivo, ECN textiles also preserved the antifungal efficacy of ECN on cutaneous candidiasis infection in mice. Ex vivo percutaneous absorption studies demonstrated that ECN released from pharmaceutical textiles concentrated more in the upper skin layers, where the fungal infections develop, as compared to dermal absorption of Pevaryl®. Overall, these results showed that this technology is promising to develop pharmaceutical garments textiles for the treatment of superficial fungal infections.