Formulation development, in vivo bioequivalence and pediatric PBPK modeling studies of taste-masked ciprofloxacin chewable tablets.

A taste-masked chewable tablet of ciprofloxacin using ion exchange resin Kyron T-134 for enhancing compliance for the paediatric population was developed. The drug-to-resin ratio was optimized for maximum taste masking by studying the effects of soaking time (X1) and mixing time (X2) on complexation (%) using Central Composite Rotatable Design (CCRD). The resin complexes were characterized by bitterness score, DSC, FTIR, and PXRD. The complex was further formulated and optimized into chewable tablets through full factorial design, The optimized formulation was subjected to a bioequivalence study, and a virtual approach of PBPK modelling was adapted to predict the pharmacokinetics of the drug in the paediatric group. The drug resin ratio of 1:1.5 yielded an optimum drug loading of 99.05%. The optimized formulation shows minimum disintegration time with more than 99% drug release within 30 min. The formulation F-9 was found to be bioequivalent with a geometric mean ratio of Cmax, Tmax, AUC0-t, and AUC0-∞ within 90% CI. It was concluded that quality by design approach can successfully be applied to optimize the drug resin ratio and PBPK modeling is a successful predictive tool for estimating the pharmacokinetics of ciprofloxacin HCl in the paediatric population.

Modification and validation of liquid chromatographic method for the quantification of ciprofloxacin in human plasma and its application to a bioavailability study.

A new simple, accurate, precise and sensitive liquid chromatographic method for the analysis of Ciprofloxacin in human plasma, suitable for quantification of drug was developed and validated using HPLC-UV method. The analyte was chromatographically separated from endogenous plasma components on a C-18 reversed phase column (5µm, 25cm × 0.46cm) and detected at 278nm. The sample pretreatment was carried out with acetonitrile on 200µl of plasma. The Lower limit of quantification (LLOQ) was 0.04 µg/ml with linearity in the range 0.04-4 µg/ml and coefficient of correlation value (R2)>0.995. The method was successfully validated as per current FDA guidance for necessary parameters and applied to a pilot bioavailability study conducted on six healthy volunteers with marketed Ciprofloxacin 250mg immediate release tablets. The plasma concentrations were subjected to non-compartmental analysis for calculation of pharmacokinetic parameters like Cmax, Tmax, AUCo-t, AUC 0-∞ and t½ etc. The mean values of Cmax and Tmax were found to be 1.35±0.09µg/ml and 1.25±0.27h respectively while for other pharmacokinetic parameters including AUCo-t, AUC0-∞ were found to be 5.98±0.96 µg/ml×h and 6.34±1.07µg/ml×h. The drug exhibited half-life (t½) of 3.94±0.33h. The obtained results proved the suitability of the method for routine pharmacokinetic studies of Ciprofloxacin.