Pharmacokinetic and drug interaction studies of Pefloxacin with paracetamol [NNAID] in healthy volunteers in Pakistan

In the present study, the pharmacokinetic and drug interaction evaluation of two drugs pefloxacin and paracetamol was carried out by a single-dose, two-treatment and two-sequence crossover design. Total fifteen healthy volunteers participated out of which ten completed the study. All were male volunteers, aged 22.36 years [means], with a mean weight of 76.45 +/- 12.05 Kg. The washout period between treatments was 5 week. Initially the method utilized for quantitative analysis of the drug was developed which was further validated. The study involved plasma protein precipitation with ethyl acetate and detection was done at 275nm. The retention time for pefloxacin 18 +/- 1 min and paracetamol were approximately 6 +/- 1 min, respectively. The calibration curve for pefloxacin was linear in the concentration range of 0.125-12.0 micro g/ml with r[2]=0.9987 in plasma. Standard concentration solution was maintained on the same temperature as that of volunteer's samples to optimize the periods for the determination of drug concentration in the plasma samples. Blood samples were collected from volunteers at different time intervals. The pharmacokinetics and drug interaction studies were anticipated by plotting concentration versus time-profiles. The value of AUC[0-infinity] in control was 67.355 +/- 3.174 micro g.h/ml, in treatment 61.242 +/- 3.868 micro g.h/ml along with relative bioavailability =91.395 +/- 4.864. Under the control and treatment condition the mean maximum plasma concentrations were found to be 4.679 +/- 0.248 micro g/ml and 4.6595 +/- 0.266 micro g/ml respectively. The average T[max] for plasma concentrations was 1.819 +/- 0.1743hr and 1.605 +/- 0.1134hr respectively. The biological half-lives in the two phases of studies were found to be 7.953 +/- 0.33hr in control and 7.7257 +/- 0.355hr in treatment. No significant effect were observed on the bioavailability and pharmacokinetics of pefloxacin by the concomitant administration with paracetamol, however very minor effect were observed that might be related with inter-individual variation in human volunteers. This pharmacokinetic studies also indicated that the level of drug [Cmax] do not differ from previous studies in different races

Development and validation of a HPLC method for determination of pefloxacin in tablet and human plasma

Developing and validating a simple, efficient, reproducible and economic reversed phase high performance liquid chromatographic [RP-HPLC] method for the quantitative determination of pefloxacin in bulk material, tablets and in human plasma. A shim-pack CLC-ODS column and a mobile phase constituting acetonitrile: 0.025 M phosphoric acid solution [13:87 v/v, pH 2.9 adjusted with KOH] was used. The flow rate was 1 ml/min and the analyses performed using ultraviolet [UV] detector at a wavelength of 275 nm using acetaminophen as an internal standard. The developed method showed good resolution between pefloxacin and acetaminophen. It was selective to pefloxacin and able to resolve the drug peak from internal standard and from formulation excipients. The percentage of coefficient variation [CV] of the retention times and peak areas of pefloxacin from the six consecutive injections were 0.566% and 0.989%, respectively. The results showed that the peak area responses are linear within the concentration range of 0.125 mg/ml-12 mg/ml [R2=0.9987]. The limits of detection [LOD] and limits of quantitation [LOQ] for pefloxacin were 0.03125 mg/ml and 0.125 mg/ml. The intra-day and inter-day variation, RSD were 0.376-0.9056 and 0.739-0.853 respectively; also, inter-day variation with relative standard deviation [RSD] were 0.1465-0.821 in plasma. The accuracy results of 70%, 100%, and 130% drugs were 100.72%, 100.34%, and 100.09%, respectively. The method is linear, quantitative, reproducible and could be used as a more convenient, efficient and economical method for the trace analysis of drug in biological fluids, in raw material and tablets

Use of avicel and spray dried lactose in the development of levofloxacin 250mg tablets by direct compression method

In present study a formulation of Levofloxacin tablet 250mg was prepared by direct compression method, using two directly compressible excepients, i.e Avicel PH101 [62.5mg] and spray dried lactose [62.5mg] with magnesium stearate [5mg] as lubricant glidant on Erweka single punch machine. These tablets are round in shape having mean weight of 373.55 +/- 8.463mg with mean diameter and thickness of 12.3 +/- 0.03mm and 2.4 +/- 0.11mm. The hardness of the tablets was 12 +/- 0.39kg. Friability of tablets were 0.67% using Roche friabilator and disintegration time was 10 min in Erweka basket rack assembly. Dissolution test was performed on USP apparatus-I and%Q was found to be 94.59. Assay results was 100.54% when performed by HPLC technique using CIS column. This formulation gives excellent results using minimal excepient and simple manufacturing procedure. This type of work gives direction to try to make formulation simple and cost effective. As direct compression method is not cheap in terms of raw materials but also produces batch in short period of time. Moreover considering biopharmaceutical aspects, tablet manufactured by direct compression dissolved rapidly in gastrointestinal tract due to prime particle dissociation as compared to that of wet granulation method