The tape-stripping technique as a method for drug quantification in skin.

Quantification of drugs within the skin is essential for topical and transdermal delivery research. Over the last two decades, horizontal sectioning, consisting of tape stripping throughout the stratum corneum, has become one of the traditional investigative techniques. Tape stripping of human stratum corneum is widely used as a method for studying the kinetics and penetration depth of drugs. This paper shows the applications of the tape stripping technique to quantify drug penetration through the skin, underlining its versatile application in the area of topical and transdermal drugs.

Determination of poloxamer 188 and poloxamer 407 using high-performance thin-layer chromatography in pharmaceutical formulations.

Poloxamers (PXMs) are amphiphilic non-ionic block polymers commonly used in the cosmetic and pharmaceutical industries. In spite of the wide use of PXMs, few studies have dealt with the analysis of these polymers in pharmaceutical preparations. In this work, high-performance thin-layer chromatography (HPTLC) has been used to quantify both PXM-188 and PXM-407 in pharmaceutical preparations. The separation of these compounds was carried out using reverse phase HPTLC plates with a chloroform-methanol mixture as the mobile phase. Detection was performed densitometrically using the Dragendorff's reagent for the visualization of PXMs. Quality parameters were established, and the detection limits ranged from 24 to 47ng/spot. A good precision (day to day and run to run), with relative standard deviations <11.18%, was obtained. The proposed method was satisfactorily applied to the analysis of laboratory-made and commercial pharmaceutical products.

Applications of thermo-reversible pluronic F-127 gels in pharmaceutical formulations.

It is, sometimes, desirable to maintain a constant plasma drug concentration within the therapeutically effective concentration range. The use of high viscosity hydromiscible vehicles such as hydrophilic gels, is one of various approaches for controlled drug delivery, and represents an important area of pharmaceutical research and development. Of these systems, Pluronic F-127 (PF-127) provides the pharmacist with an excellent drug delivery system for a number of routes of administration and is compatible with many different substances. Gels containing penetration enhancers have proven to be especially popular for administering anti-inflammatory medications since they are relatively easy to prepare and very efficacious.

Evaluation of the enhanced oral effect of omapatrilat-monolein nanoparticles prepared by the emulsification-diffusion method.

In the present study, the emulsification-diffusion method was optimized in order to obtain omapatrilat/monolein-nanoparticles (omapatrilat/MO-nanoparticles). The antihypertensive effect of omapatrilat/MO-nanoparticles in spontaneously hypertensive rats (SHR) after oral administration was evaluated. The results indicated that the variables involved in the process did not have an influence on particle size, and that the former is directly determined by the amphiphilic properties of MO. When SHR were orally treated with omapatrilat/MO-nanoparticles, blood pressure was significantly reduced and completely normalized after three days. This effect was markedly higher than that observed with omapatrilat suspensions. The effect of omapatrilat/MO-nanoparticles can be attributed to: (i) The molecular dispersion of the drug into the lipophilic domain of monolein's bicontinuous phase; (ii) the adhesive properties of the nanodispersion on the gastrointestinal mucosa; (iii) the high surface area of the dispersion; (iv) the intraluminal interaction between MO, the mixed micelles arising from the digestive process, and omapatrilat; and (v) the well-known absorption-promoting properties of lipids, and in particular, of MO. MO-nanoparticles can be an interesting system to increase the oral bioavailability of drugs.

Preparation and characterization of triclosan nanoparticles for periodontal treatment.

The aim of this work was to produce and characterize triclosan-loaded nanoparticles (NPs) by the emulsification-diffusion process, in an attempt to obtain a novel delivery system adequate for the treatment of periodontal disease. The NPs were prepared using poly(D,L-lactide-co-glycolide) (PLGA), poly(D,L-lactide) (PLA) and cellulose acetate phthalate (CAP). Poly(vinyl alcohol) (PVAL) was used as stabilizer. Batches were prepared with different amounts of triclosan (TCS) in order to evaluate the influence of drug on NP properties. Solid NPs of less than 500 nm in diameter were obtained. Entrapment efficiencies were higher than 63.8%. The characterization by scanning electron microscopy and light scattering indicated that high concentrations of TCS seemingly caused the increase of NP mean size. A decrease in the PLGA glass transition temperature was observed by differential scanning calorimetry. This could indicate that TCS in PLGA-NPs behaves as a non-conventional plasticizer. Subsequently, in vitro release studies were carried out under sink conditions using a device designed in our laboratory to allow a direct contact between the particles and the dissolution medium. A fast release of TCS from NPs was detected. A preliminary in vivo study in dogs with induced periodontal defects suggested that TCS-loaded NPs penetrate through the junctional epithelium.

Skin permeation enhancement by sucrose esters: a pH-dependent phenomenon.

The purpose of the present study was to evaluate the effect of sucrose esters (particularly, sucrose laureate and sucrose oleate in Transcutol) on the percutaneous penetration of a charged molecule as a function of ionization. We have investigated the influence of these sucrose esters on the in vitro diffusion profiles of lidocaine hydrochloride, a weak ionizable base (pKa=7.9), at different pH values, using porcine ear skin as the barrier membrane. As expected, lidocaine flux in the absence of an enhancer, increased from pH 5 to 9 with a corrresponding increase in the level of the unionized base. However, when skin was pretreated with 2% laureate in Transcutol (2% L-TC), drug permeation was higher at pH 5.0 and 7.0 than at 9.0. A different trend was observed in experiments with 2% oleate in Transcutol (2% O-TC), where skin flux was maximal at a more basic pH, when the degree of ionization is low. The results suggest that sucrose laureate enhances the penetration of the ionized form of the drug (12-fold greater flux relative to control), whereas sucrose oleate is more effective in promoting permeation of the unionized species. The structural properties of the sucrose esters as well as the degree of ionization of the drug are important characteristics affecting the transdermal flux of lidocaine.

Microneedles as transdermal delivery systems: combination with other enhancing strategies.

Transdermal drug delivery has exhaustively been studied over the past decades due to its multiple advantages over other administration routes; however, drugs that can be administered by this via are few owe to the stratum corneum permeability properties. Recently, several strategies to bypass the upper-layer skin barrier have been developed. One of the latest advances in this area has been the use of micro-scale needles, which painlessly pierce skin, increasing the passage of drugs with unfavourable skin permeability (i.e., low potent, hydrophilic, high molecular drugs) by several orders of magnitude, by bypassing the stratum corneum. Microneedles have shown to be safe and easy-to-use for drug administration, a nouvelle alternative to hypodermic needle injections, and an array in which drugs can be included to attain a controlled release as to achieve a higher drug delivery. Several works have demonstrated that such devices dramatically increase transdermal delivery of large molecules, thus nowadays microneedles have been regarded as a potential technology approach to be employed alone or with other enhancing methods such as electroporation and iontophoresis, as well as with different drug carriers (e.g., lipid vesicles, micro- and nanoparticles). Hence, this review is mainly focused on presenting the results obtained when combining microneedles with a variety of strategies to ease drug diffusion through skin, including physical enhancers and drug carrier systems.

Influence of sucrose esters on the in vivo percutaneous penetration of octyl methoxycinnamate formulated in nanocapsules, nanoemulsion, and emulsion.

The influence of sucrose laureate and sucrose oleate on the in vivo percutaneous penetration of octyl methoxycinnamate (OMC) formulated in i) colloidal suspensions (nano-emulsions and nanocapsules), and ii) conventional o/w emulsions was evaluated. The results showed that nano-emulsions formulated with sucrose laureate exhibited the highest penetration in the stratum corneum compared to the other formulations. A two-fold increase in OMC skin deposition was observed with the nano-emulsion containing sucrose laureate when compared to the control. The data obtained suggest that the total amount of OMC detected in the stratum corneum and the penetration depth are strongly dependent upon the formulation's nature, the particle size, and the type of enhancer.

Relationship between the swelling process and the release of a water-soluble drug from a compressed swellable-soluble matrix of poly(vinyl alcohol).

An attempt was made in this study to relate the release of a highly water-soluble model drug from tablet matrices of poly(vinyl alcohol) (PVAL) with the factors that may affect the release behavior. Swelling was evaluated using a simple projection method. The swollen layer was photographed to monitor its thickness. The polymer and drug dissolution were determined simultaneously by spectrophotometric methods. The resulting change of tablet area showed that the process of swelling occurred in three different stages that were intimately related to polymer dissolution: (a) a rapid initial swelling, resulting in an increased area; (b) a period with an approximately constant area; and (c) a decrease of the tablet area. In spite of the significant dissolution of PVAL during the release process, the thickness of the gel layer gradually increased. Thus, the delivery was governed by the drug concentration gradient along the diffusional path length. The drug release appeared to be controlled by a diffusion process according to Higuchi-type kinetics. The data analysis of drug and polymer profiles confirmed the diffusional mechanism.

The effect of keratolytic agents on the permeability of three imidazole antimycotic drugs through the human nail.

The permeability of three imidazole antimycotics (miconazole nitrate, ketoconazole, and itraconazole) through the free edge of healthy human nail was evaluated in vitro using side-by-side diffusion cells. The influence of keratolytic substances (papain, urea, and salicylic acid) on the permeability of the antimycotics was also studied. The results suggested that the nail constituted an impermeable barrier for these antimycotics; it could be considered that the nail behaved as a hydrophilic gel membrane, through which drugs of low solubility could not permeate. The use of ethanol did not promote the passage of any of the antimycotic drugs. Although scanning electron microscopy indicated that the keratolytic substances had a significant effect on the nail surface (papain > salicylic acid > urea), the passage of the three antimycotics was not improved by pretreatment with salicylic acid alone (20% for 10 days), or by the application of the drug in a 40% urea solution. It was found that only the combined effects of papain (15% for 1 day) and salicylic acid (20% for 10 days) were capable of enhancing the permeability of the antimycotic.

Influence of the stabilizer coating layer on the purification and freeze-drying of poly(D,L-lactic acid) nanoparticles prepared by an emulsion-diffusion technique.

In this study, the purification by cross-flow filtration (CFF) and freeze drying of poly(D,L-lactic acid) (PLA) nanoparticles prepared by an emulsion-diffusion technique using poly(vinyl alcohol) (PVAL) or poloxamer 188 (P-188) were investigated. The stability of the suspensions was correlated to the affinity of the stabilizers for the nanoparticle surface, the resistance of the coating layer to continuous filtration and to freeze-thawing procedures. The results indicated a clear difference between the two stabilizers, suggesting that the nature of the coating layer has a very important role during CFF and freeze-drying. Nanoparticles prepared with PVAL were filtered and freeze-dried without nanoparticle fusion. This behaviour was attributed to the formation of a stable thick layer (similar to that found for polystyrene latex). In contrast, aggregation of nanoparticles was observed during CFF for the batches prepared with P-188, indicating that the polypropylene oxide blocks present in the copolymer have little affinity for the PLA surface. However, these suspensions were successfully recovered when using stabilizer solutions as diafiltration media, suggesting a dynamic exchange between the P-188-adsorbed chains and those of the identical polymer remaining in the bulk solution. The presence of P-188 did not prevent nanoparticle aggregation after freeze-drying. Therefore, the use of cryoprotectants was necessary. Aggregation may have been due to an increase in the solubility of P-188 in the bulk solution, which provokes a destabilization of the suspension by desorption and partial coverage of the surface. The best cryoprotectants were found to be sugars containing glucose units. The cryoprotective effect was related to the hydrogen bonding capability of these sugars, which prevented aggregation by dehydration of P-188 forcing it to the PLA surface.