The influence of the polar head and the hydrophobic chain on the skin penetration enhancement effect of poly(ethylene glycol) derivatives.

The effect of a homologue series of nonionic surfactants, namely poly(ethylene glycol) (PEG) fatty acid esters, differing in oxyethylene (PEG 8, PEG 12, and PEG 40) and fatty acid (stearate, mono and di-laurate, and mono and di-oleate) chain lengths, on in vitro skin permeability of ketoprofen (KTP) vehicled in plasters was investigated. The drug diffusion through hairless mouse skin as well as the effect of the surfactant type and strength was studied by Franz diffusion cells and ATR-FTIR spectroscopy. The use of PEG stearate series revealed that the surfactant with the largest polar head, namely PEG 40, was ineffective in enhancing the skin permeation of KTP, independently of the plaster concentrations. The effect of the hydrophobic chain was investigated only by using the shortest oxyethylene chains. The experimental results revealed that the oxyethylene chain length of surfactants appeared to be more influent than the alkyl chain. The prediction of the absorption enhancing capability of these PEG derivatives appeared related to the vehicle other than the proper combination of the number of ethylene oxide groups and alkyl groups.

Efficacy and safety of piroxicam patch versus piroxicam cream in patients with lumbar osteoarthritis. A randomized, placebo-controlled study.

UNLABELLED: In order to assess the efficacy and safety of a new patch containing 14 mg of piroxicam (CAS 36322-90-4) 1%, applied once daily, in comparison with a reference marketed formulation, piroxicam 1% cream applied three times a day, placebo patch applied once daily, a randomized, placebo-controlled, parallel-group clinical trial was carried out by general practitioners in patients with lumbar osteoarthritis aged between 18 and 75 years. Pain during daily activities scored on a 100 mm visual analogue scale was the primary outcome measure. Other secondary outcome measures were pain on isometric contraction, on full passive motion, and on pressure, and functional disability. Statistical analysis was performed on the differences between the three groups in the intention-to-treat population (ITT). One hundred and eighty patients were enrolled. The available ITT population comprised 179 patients. The compliance was very good. Decrease in pain score during daily activities after the eight days of study treatment (at the final visit, Vf) was 42.2%, 41.7% and 25.8% in the piroxicam patch, piroxicam cream and placebo groups, respectively. The difference between the pain scores in two active treatments arms was not statistically significant at the Vf whereas the differences between the pain scores of two active treatment arms vs the placebo arm were statistically significant validating the study design. All efficacy measures improved during the study, for both the active treatment groups, and the results for the secondary efficacy variables were generally consistent with those concerning the main efficacy criterion. The difference between the two active treatments in pain during daily activities were statistically significant at the final visit; in fact the 95% CI of the difference between the mean of responder rate of the piroxicam patch and piroxicam cream was -18.3%, +24.4% indicating a trend of superiority of the piroxicam patch versus the cream (per-protocol analysis). The data obtained during the intermediate visit (V2, day 4) allow us to assess that the piroxicam patch was on average better than the piroxicam cream in terms of fast pain reduction (change from baseline: - 29.1% for piroxicam patch in comparison to -24.6% for piroxicam cream). Moreover the piroxicam patch proved to be on average more effective than the piroxicam cream in terms of secondary efficacy endpoints. Safety was considered satisfactory in all groups. CONCLUSIONS: The piroxicam patch is effective in the treatment of lumbar osteoarthritis and has demonstrated to be well tolerated and it improves patients compliance. The piroxicam patch offers a comparable alternative to the marketed piroxicam cream for the treatment of lumbar osteoarthritis with the advantage of a better compliance with the once a day application of the patch compared to three daily applications for the piroxicam cream.

Fast HPLC method for the determination of ketoprofen in human plasma using a monolithic column and its application to a comparative bioavailability study in man.

A fast, specific, accurate, precise and reproducible high-performance liquid chromatography (HPLC) method with diode-array detector (DAD) was developed and validated for the determination of ketoprofen (CAS 22071-15-4) in human plasma using flubiprofen (CAS 5104-49-4) as an internal standard. The chromatographic separation was achieved on an onyx monolithic C18 (100 x 4.6 mm) analytical column with an isocratic mobile phase consisting of acetonitrile/potassium dihydrogen phosphate (KH2PO4) 0.01 M, (40:60, v/v) adjusted to pH 3.5. The flow was set at 5 ml x min(-1) and the wavelength at 254 nm. The total analysis time was less than 5 min. The ratio of peak area of analyte to internal standard was used for quantification. The limit of detection was defined as the ketoprofen concentration that produced a signal-to noise ratio greater than 3. The lower limit of quantification (LLOQ) was 10 ng x m(-1). At this level, the relative standard deviation (RSD) was lower than 13%. The calibration curve was linear over the concentration range 1-500 ng x ml(-1) with a minimum detectable limit of 10 ng x ml(-1). The coefficients of variation for the inter-day and intra-day assay were found to be less than 11%. The present method was successfully applied to the routine analysis of human plasma samples collected from healthy volunteers after dermal application of two topical formulations containing ketoprofen in order to assess the relative bioavailability and to demonstrate that the systemic bioavailability of ketoprofen administered topically is low enough to ensure a low incidence of gastrointestinal adverse events.