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

Abstract

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 2³ factorial design was adopted to develop poly-ϵ-caprolactone (PCL) celecoxib-loaded microparticles (F1–F8). To minimize drug-percentages released before colon, another coat of Eudragit^® 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 μm. 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.

Keywords::

• Inflammatory bowel disease
• factorial design
• time-dependant coat
• pH-dependant coat
• pharmacokinetics