Controlled in vivo release of nicorandil from a carvone-based transdermal therapeutic system in human volunteers

The aim of our present study was to prepare and evaluate a carvone-based transdermal therapeutic system (TTS) of nicorandil to find its ability in providing the desired in vivo controlled release profile on dermal application to human volunteers. The effect of EVA 2825, and adhesive-coated EVA 2825, and adhesive-coated EVA 2825-rat skin composite on the in vitro permeation of nicorandil from a carvone-based HPMC gel drug reservoir was studied against a control (rat abdominal skin alone). The carvone-based drug reservoir system was sandwiched between adhesive-coated EVA 2825-release liner composite and a backing membrane. The resultant drug reservoir sandwich was heat-sealed to produce a circle-shaped TTS (20 cm²) that was subjected to in vivo evaluation on dermal application to human volunteers against oral administration of immediate-release tablets of nicorandil. The carvone-based TTS provided a steady-state plasma concentration of 20.5 ng/ml for ∼24 hr in human volunteers. We concluded that the carvone-based TTS of nicorandil provided the desired in vivo controlled-release profile of the drug for the predetermined period of time.     

Enhancing of tuberculin allergy by previous tuberculin testing

A controlled study on the enhancing of tuberculin allergy by one or more earlier tuberculin tests was carried out in a previously untested and unvaccinated population, in an area where the prevalence of non-specific allergy was known to be high. The results have shown that a test with 1 TU of PPD RT 23 in Tween 80 diluent causes subsequent tests to elicit significantly larger reactions. This enhancing effect is more marked among those with initial reactions of 8-13 mm to 1 TU or 10 mm and more to 20 TU. There is practically no enhancement among those whose reactions to 20 TU measure 0-4 mm or even 0-9 mm. Even in the group with reactions of 10 mm and more to 20 TU only some individuals show evidence of enhancement. The enhancing of allergy increases with age.     

A validated stability indicating ion-pair RP-LC method for zoledronic acid

The present paper describes the development of a stability indicating high performance liquid chromatographic (HPLC) assay method for zoledronic acid in the presence of its impurities and degradation products generated from forced decomposition studies. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation of zoledronic acid was observed under oxidative stress at higher temperature. The drug was found to be stable in other stress conditions attempted. Successful separation of the drug from the degradation products formed under stress conditions was achieved on a C18 column using a mixture of phosphate buffer that contains 7 mM tetra butyl ammonium hydrogen sulphate, an ion-pairing agent and methanol (95:5) as mobile phase. The developed HPLC method was validated with respect to response function, precision, accuracy, specificity and robustness. The developed HPLC method to determine the related substances and assay determination of zoledronic acid can be used to evaluate the quality of regular production samples. It can be also used to test the stability samples of zoledronic acid.