Rapid high-performance liquid chromatographic analysis of procainamide and n-acetylprocainamide in plasma

A simple, rapid and reproducible high performance liquid chromatographic [HPLC] method for the determination of procainamide [P A] and its main metabolite N- acetylprocainamide [NAPA] in plasma has been developed and validated. The assay is performed after single extraction of PA, NAPA and atenolol [internal standard] from alkalinized plasma into chloroform. The drugs and the internal standard were eluted from adsorbsphere phenyl column with a mobile phase consisting of methanol:water [27:73%, v/v] containing 0.03% triethylamine and adjusted with acetic acid to an apparent pH 4.5 at a flow rate of 1 ml/min. The effluent was monitored with a fluorescence detector set at 281 nm excitation wavelength and 356 nm emission wavelength. Standard curves for the analytes in plasma were linear [r > 0.999] in the range of 0.25-10 [micro]g/ml for PA and 0.1-10 micro g/ml for NAPA. The intraday coefficient of variation [CV] ranged from 2.58% to 6.32% for PA and from 0.95% to 2.60% for NAPA at three different concentrations. The interday CVs varied from 1.02% to 5.79% for P A and from 0.84% to 2.60% for NAPA. The relative recoveries of P A ranged from 90% to 104% and for NAPA from 95.3% to 108.0%. The method is applied for the determination of the pharmacokinetic parameters of P A and NAPA after oral administration of P A Durules [500 mg] tablet to five beagle dogs

Effect of accelerated storage conditions on the dissolution and bioavailability of amitriptyline from sustained release capsules

Amitriptyline commercially available as sustained release capsules was stored at different conditions of temperature and relative humidity [RH] namely ambient room temperature and humidity 40°C/30 RH and 40°C/80% RH. The dissolution rate profiles before and after storage were compared. The bioavailability of amitriptyline in beagle dogs before storage was compared to that after storage at ambient conditions and stressed conditions [40°C/80% RH]. A remarkable change in the physical appearance was observed when the capsules were stored for16 weeks at 40°C/80% RH as the beads inside the hard gelatin capsules were agglomerated. A small ddecrease in dissolution rate was observed for capsules stored at 40°C/30% RH [up to 16 weeks] and at ambient conditions [up to 50 weeks]. An initial decrease in the percentage dissolved after 2 weeks of storage at 40°C/80% RH was noticed, followed, followed by a considerable increase upon storage for 16 weeks. The rate and extent of absorption from capsules stored at ambient conditions for 50 weeks were equivalent to those from pre-storage capsules. However a significant decrease in the rate and extent of absorption was observed for capsules stored for 16 weeks at 40°C/80% RH. Degradation and/or complexation of amitriptyline with the excipients in the formulation might explain the poor bioavailability for capsules exposed to stressed conditions

Effect of formulation and penetration enhancers on percutaneous absorption of haloperidol

The purpose of this study was to investigate the effect of formulations and penetration enhancers on the percutaneous absorption of haloperidol. Several transdermal haloperidol get formulations were prepared using different polymers. These formulations were evaluated invitro utilizing improved franz diffusion cells. The highest amount of haloperidol [373.23 micro g] delivered in 24 hrs through rabbit skin was achieved by using methylcellulose as a gel forming polymer. Different enhancers including azone, oleic acid lecithin and 1.8 cineole were added to methylcellulose gel formulation in various concentrations [3.0, 6.0 and 9% w/w]. among the various permeation promoters tested 1.8 cineole was the most effective agent for enhancing the percutaneous absorption of haloperidol from methylcellulose gel formulation. It was found that 1.8 cineole and azone have enhanced transdermal delivery of the drug by 6.16 and 3.56 fold respectively. On the other hand the formulation containing lecithin did not show significant difference from the control, while oleic acid showed a decrease in the amount of haloperidol transported across the skin as compared to control

Effect of colestipol on indomethacin pharmacokinetics in rabbits

The purpose of this investigation was to determine whether the oral administration of colestipol would increase the systemic elimination of indomethacin following intravenous administration [2mg/kg] to rabbits. Adsorption studies in-vitro were also performed. The in-vivo results indicate that colestipol do not affect the serum levels of indomethacin. The values during colestipol treatment colestipol do not affect the serum levels of indomethanic. The values during colestipol treatment were lower than those for the control, but the differences in concentrations were not significant. No significant differences were observed in any of the calculated pharmacokinetic parameters between the control and colestipol treated rabbits. This in-vitro adsorption studies supported the in-vivo results. colestipol was found to have a poor adsorption capacity for indomethacin. The Freundlich constant [K] for adsorption was 0.9mg/g at equilibrium [3h]. Furthermore, three successive washings of the drug- adsorbent mixture, with 20 mL buffer solution, resulted in 33.8% desorption. Based on the in-vivo andin-vitro studies it is not likely that the administration of colestipol will result in a change in the pharmacokinetic parameters of indomethanin in man