High performance liquid chromatographic method for determination of doxycycline in human plasma and its application in pharmacokinetic studies

An accurate, sensitive and reproducible high performance liquid chromatographic [HPLC] method for the quantitation of doxycycline in plasma has been developed and validated. The drug and the internal standard were eluted from a micro-Bondapak C [18] column [3.9 mm x 150 mm, I.D., 5 micro m particle size] at room temperature with a mobile phase consisting of acetonitrile and water [28:72,% v/v]. The flow rate was 0.8 ml/min. A UV detector set at 346 nm was used to monitor the effluent. Each analysis required no longer than 6 min. Quantitation was achieved by measurement of the peak area ratio of the drug to the internal standard. The limit of detection was 10.0 ng/ml and the limit of quantification of doxycycline in plasma was 0.10 micro g/ml. The standard curve ranged from 0.1 to 2.5 micro g/ml. The intraday coefficient of variation [C.V.,%] ranged from 1.444 to 3.016%, and interday [C.V.,%] from 1.572 to 2.705% at four different concentrations. The relative recoveries ranged from 98.43 to 105.13% and the absolute recoveries ranged from 54.08 to 62.56% at four different concentrations. Stability studies showed that doxycycline is stable for at least 4 weeks in plasma after freezing at - 20 °C. The method was applied for the determination of the pharmacokinetic parameters of doxycycline after oral administration of 100 mg capsules of two commercially available formulations to 6 human volunteers

In-vitro and in-vivo evaluation of commercial and microencapsulated sustained release tablets containing diclofenac sodium

Diclofenac sodium microcapsules were prepared using the phase separation technique induced by non-solvent addition. Ethl1cellulose and Eudragit RS100 were used as well forming materials in two core: wall ratios [1: 1 and 1: 2]. The prepared microcapsules were compressed into tablets without excipients. The influence of tableting type of wall forming material and the core: wall ratio on the release pattern of the drug from microcapsules were determined in Ph 1.2 and pH 6.8. compression of the microcapsules significantly [p < 0.05] decreased the rate of drug release due to the reduction of the surface area. Less than 2.0% of the drug was released in 0.1N HC1 during the first two hours of dissolution from microcapsules before and after tableting. On the other hand, the dissolution results of the tableted ethy1cellulose microcapsules with 1:1 and 1:2 core: wall ratios showed that 88.6 and 70.6% of the drug were released to the phosphate buffer solution, while only 45.0 and 24.4% of the drug in the tableted eudragit microcapsules was released within 8 h of dissolution. The tableted ethy1cellulose microcapsules with 1:2 core: wall ratio showed almost identical release of the drug as that from commercial tablets therefore, it was chosen for bioavailability study in six beagle dogs. The in-vivo data showed that the tableted microcapsules gave bioavailability of 87.5% relative to that of the commercial voltaren retard tablets. The prepared tablets show that it is possible to use ethy1cellulose microcapsules to prepare tablets that are pharmaceutically and biologically equivalent to those of the commercially available voltaren retard tablets

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