Capsaicin delivery into the skin with lipidic nanoparticles for the treatment of psoriasis.

The study aims to explore the potential of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) in improving the topical delivery of capsaicin (CAP) by in vitro and in vivo studies. The lipidic nanoparticles were prepared by solvent diffusion method and were characterized for average particle size, zeta potential and entrapment efficiency. TEM photomicrographs revealed that the particles were nanometric in size. Higher amount of CAP can be encapsulated in the NLCs (87.4 ± 3.28) as compared with SLNs (79.7 ± 2.93%). The cumulative amounts of CAP permeated through the skin and retained in the SC were higher in the case of NLCs as compared with plain drug solution and SLNs. SLNs and NLCs exhibited minimum to no irritation. All the results concluded that NLCs and SLNs have shown a good ability to increase drug accumulation in the various skin layers but NLCs may be a more potential carrier for topical delivery of CAP for an effective therapy of psoriasis.

Pharmacokinetic study of borneol and menthol in rats after oral administration of qingyan drop pills.

Both borneol and menthol are bioactive substances derived from Chinese herbal medicines. In order to understand the pharmacokinetics of borneol and menthol in Qingyan drop pills, a rapid, sensitive, and simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the simultaneous determination of borneol and menthol in rat plasma. Sample preparations were carried out by liquid-liquid extraction (LLE) with an internal standard solution of naphthalene. The analytes and internal standard (IS, naphthalene) were separated well on an HP-1 capillary column. The pharmacokinetic parameters were estimated by a compartmental method using the Phoenix WinNonlin software program (Version 6.0). The standard curves were linear over a wide concentration range of 2.5-50.0 ng/µL ( R = 0.9963), 8.7-62.2 ng/µL ( R = 0.9994) for both borneol and menthol in plasma, respectively. The limits of quantification (LOQ) of borneol and menthol in plasma were 2.4 ng/µL and 5.0 ng/µL, respectively. The intra-day precisions for borneol and menthol were < or = 10.0 % R. S. D. at the LOQ and < or = 6.0 % at higher concentrations. The average value of CMAX was 18.97 ± 2.71 ng/µL with a TMAX at 20.00 ± 0.00 min for borneol after oral administration of the drop pills; for menthol, the average value of CMAX was 79.02 ± 11.40 ng/µL with a TMAX at 25.00 ± 4.40 min. This validated assay method was successfully applied to a pharmacokinetic study of borneol and menthol after oral administration of Qingyan drop pills in rat. The results showed that the kinetics of borneol and menthol can be described by an open one-compartment model. The pharmacokinetic parameters provide some information for clinical administration of Qingyan drop pills.

Topical capsaicin. The fire of a 'hot' medicine is reignited.

IMPORTANCE OF THE FIELD: Capsaicin and its receptor, TRPV1, occupy a central place in current neurophysiological studies regarding pain transmission and have opened new avenues for understanding the role of transient receptor potential (TRP) receptors in itch processing. Substantial efforts in drug discovery are at present directed at vanilloid receptors for finding new remedies for pain and itch. AREAS COVERED IN THIS REVIEW: We provide an overview of the major clinical indications of capsaicin, primarily targeting pain and itch of various origins, with an emphasis on the usefulness of capsaicin in treating pruritus and dermatological conditions. In particular, we cover the most relevant findings in recent years, from 2000 onward (although seminal discoveries and studies are discussed irrespective of their date of publication if deemed essential for understanding capsaicin's actions). WHAT THE READER WILL GAIN: Readers are offered a broad perspective on the areas of clinical application of capsaicin, emphasizing its usefulness in the treatment of neurophatic pain and pruritus of various origins. TAKE HOME MESSAGE: Capsaicin has been proven a truly exciting molecule and remains a valuable drug for alleviating pain and itch, widely surpassing its role as a simple spicy ingredient.

Skin disposition of d-camphor and l-menthol alone and together.

The terpenes camphor and menthol are often used in topical preparations, although some data indicate concern about their skin penetration after application in most commonly used vehicles. The cutaneous disposition of these substances applied alone and together in either an oily solution or a hydrogel was evaluated ex vivo using full human skin mounted in flow-through diffusion cells. After 0.5, 1 and 2 h of application, the skin was progressively tape-stripped into three fractions of stratum corneum (SC) and the remaining epidermis with the dermis. The content of terpenes in the skin layers was determined using gas chromatography. Different penetration into the skin layers was observed depending on the type of vehicle. The highest SC absorption was noted when terpenes were applied in hydrogel, where the total content in the SC was 200 microg/cm2 for camphor and 400 microg/cm2 for menthol, and the total skin absorption was 310 and 460 microg/cm2, respectively. The SC penetration of both terpenes from the oily solution was the same (approximately equal to 35 microg/cm2). When both terpenes were present in the hydrogel the SC absorption decreased, the amounts of camphor and menthol in the SC being 50 and 190 microg/cm2, respectively (total skin accumulation was 120 and 220 microg/cm2, respectively). Such an effect was not observed for the oily solution.

Pharmacokinetics of menthol and carvone after administration of an enteric coated formulation containing peppermint oil and caraway oil.

Enteric coating of peppermint oil/caraway oil capsules avoids subjective discomfort to the patient caused by gastroesophageal reflux. In order to confirm bioequivalence of an enteric coated formulation containing peppermint oil and caraway oil (CAS 277309-55-4, Enteroplant) and an immediate release formulation of both oils, the pharmacokinetics of menthol and carvone after oral administration of the two formulations were studied in a randomized, two-period cross-over study in 16 healthy male volunteers. The subjects received 180 mg peppermint oil and 100 mg caraway oil, once as 2 enteric coated capsules of the fixed enteric coated combination preparation containing 90 mg peppermint oil (WS 1340) and 50 mg caraway oil (WS 1520) each (test) and once in the form of 5 capsules of an immediate release formulation (reference) containing 36 mg peppermint (WS 1340) oil and 20 mg caraway oil (WS 1520) each. The capsules were taken with 250 ml water after a 10 h fast. Both substances were determined in plasma by GC/MS after extraction. The limit of quantification was 10 ng/ml for menthol and 0.5 ng/ml for carvone. The mean maximum plasma levels for menthol were 1196 ng/ml after administration of the test medication and 1492 ng/ml after administration of the reference medication. The bioavailability with respect to the AUC was comparable after administration of test and reference preparation, the 90% confidence interval was 97 to 105%. As expected, there were considerable differences for Tmax. After application of the enteric coated form the maximum concentration was reached significantly later (3.0 h vs. 1.7 h) compared to the immediate release capsule. Corresponding data were also calculated for carvone. After application of the test medication the maxima of 14 ng/ml for both formulations were reached later (2.5 h vs. 1.3 h). The 90% confidence interval of the AUC for carvone was 79 to 119% and therefore slightly outside the acceptable range for bioequivalence of 80 to 125%. However, this fact should not be relevant, in particular since the dosage of the enteric coated capsule lies at the upper limit of the model text and positive clinical studies, also on the therapeutic equivalence of the two formulations, are available.

Preparation of griseofulvin for topical application using N-methyl-2-pyrrolidone.

We attempted to prepare a new griseofulvin formulation for topical application using N-methyl-2-pyrrolidone (NMP). Griseofulvin dissolves poorly in both water and oil, but dissolves in NMP to a concentration of about 100 mg/ml. A soybean oil-water emulsion with soybean lecithin and NMP as emulsifier and co-solvent, respectively, was prepared using a Microfluidizer, a high-pressure homogenizer. The size of the droplets in emulsion was about 200 nm, and the emulsion was stable for over 3 months. The skin permeation of griseofulvin through Yucatan micropig skin was studied in vitro using vertical type cells under donor phase open conditions. The permeation of griseofulvin from the NMP-water mixture (0-40%) into the skin tended to increase with increasing NMP concentration, although this finding was not statistically significant. Permeation from emulsion (oil phase, 20%; NMP 10-40%) was significantly higher than that from the water-NMP mixture. Permeation from the oil-NMP mixture was highest among the formulations investigated, and permeation from emulsion under donor phase closed conditions was significantly lower than that under open conditions. We believe that the evaporation of water from the emulsion after application to the skin was an important factor in skin permeation enhancement. When the emulsion containing 3% l-menthol was applied, a sufficient skin concentration (47 microg/cm3 in dermis) was obtained.