Colon-targeted celecoxib-loaded Eudragit® S100-coated poly-ε-caprolactone microparticles: Preparation, characterization and in vivo evaluation in rats

Context: Celecoxib suffers from low and variable bioavailability following oral administration of solutions or capsules. Recent studies proved that chemoprevention of colorectal cancer is possible with celecoxib. Objective: This work aimed to tailor colon-targeted celecoxib-loaded microparticles using time-dependant and pH-dependant coats. Estimation of drug pharmacokinetics following oral administration to fasted rats was another goal. Methods: A 2(3) factorial design was adopted to develop poly-epsilon-caprolactone (PCL) celecoxib-loaded microparticles (F1-F8). To minimize drug-percentages released before colon, another coat of Eudragit (R) S100 was applied. In vitro characterization of microparticles involved topography, determination of particle size and entrapment efficiency (EE %). Time for 50% drug release (t(50%)) and drug-percentages released after 2 hours (Q(2h)) and 4 hours (Q(4h)) were statistically compared. Estimation of drug pharmacokinetics following oral administration of double-coat microparticles (F10) was studied in rats. Results: PCL-single-coat microparticles were spherical, discrete with a size range of 60.66 +/- 4.21-277.20 +/- 6.10 mu m. Direct correlations were observed between surfactant concentration and EE%, Q(2h) and Q(4h). The PCL M. wt. and drug: PCL ratio had positive influences on EE% and negative impacts on Q(2h) and Q(4h). When compared to the best achieved PCL-single-coat microparticles (F2), the double-coat microparticles (F10) showed satisfactory drug protection; Q(2h) and Q(4h) were significantly (P < 0.01) decreased from 31.84 +/- 1.98% and 54.72 +/- 2.10% to 15.92 +/- 1.78% and 26.93 +/- 2.76%, respectively. When compared to celecoxib powder, F10 microparticles enhanced the bioavailability and extended the duration of drug-plasma concentration in rats. Conclusion: The developed double-coat microparticles could be considered as a promising celecoxib extended-release colon-targeting system.