CHITOSAN-COATED MUCOADHESIVE MICROSPHERES OF BCS CLASS II HIGH POTENCY STATIN: FORMULATION, IN VITRO AND VIVO CHARACTERIZATION
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Abstract
Background: Rosuvastatin calcium, a BCS Class II high-potency statin, has poor oral bioavailability (approximately
20%) owing to its limited solubility and narrow absorption window in the upper gastrointestinal tract. This study aimed
to develop chitosan-coated mucoadhesive microspheres of rosuvastatin calcium using the ionic gelation technique to
enhance oral bioavailability through prolonged gastric mucosal retention. Methods: Six formulations (M1–M6) of
mucoadhesive microspheres were prepared by ionic gelation using sodium alginate (1.5–2.5% w/v) as the core polymer
and chitosan (0.5–1.5% w/v) as the mucoadhesive coating. The microspheres were characterized for particle size,
polydispersity index, zeta potential, surface morphology (SEM), percentage yield, entrapment efficiency, ex vivo
mucoadhesion (wash-off test on rat gastric mucosa), and in vitro drug release. Optimized formulations (M5 and M6)
were evaluated for in vivo pharmacokinetic performance in Wistar rats (n=6) and compared with the pure drug
suspension. Results: The microspheres exhibited mean particle sizes of 452.6–589.1 μm with narrow size distributions
(PDI <0.32). Chitosan coating reversed zeta potential from negative (-28.4 to -33.8 mV) to positive (+18.6 to +26.1
mV), confirming successful surface modification. The entrapment efficiency increased with sodium alginate
concentration and chitosan coating, reaching 88.2 ± 3.1% for M6 (2.0% alginate, 1.5% chitosan). Ex vivo mucoadhesion
studies demonstrated significantly enhanced retention of chitosan-coated microspheres (68–75% after 8 hours) compared
to uncoated microspheres (42–51%), attributed to electrostatic interactions between protonated chitosan amine groups
and sialic acid residues of mucin. Formulation M6 provided a sustained drug release of 88% at 12 h. In vivo
pharmacokinetic studies revealed a 2.48-fold enhancement in relative oral bioavailability (AUC0-∞: 7412.3 ± 928.5 vs.
2987.2 ± 435.6 ng·h/mL, p<0.001), with Cmax increased 2.07-fold (854.2 ± 98.6 vs. 412.5 ± 58.7 ng/mL) and Tmax
prolonged from 2.5 to 4.0 h. Conclusion: Chitosan-coated mucoadhesive microspheres prepared by ionic gelation
represent a promising multi-particulate gastroretentive delivery system for rosuvastatin calcium, achieving substantial
enhancement in oral bioavailability through prolonged gastric mucosal retention and sustained drug release.
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Chitosan-coated mucoadhesive microspheres of rosuvastatin calcium, prepared by ionic gelation technique using sodium alginate as core polymer and chitosan as mucoadhesive coating, demonstrated excellent in vitro characteristics including suitable particle size, positive zeta potential, high entrapment efficiency, superior mucoadhesive properties, and sustained drug release. The optimized formulation M6 (2.0% sodium alginate, 1.5% chitosan) achieved a remarkable 2.48-fold enhancement in oral bioavailability in Wistar rat. These findings establish chitosan-coated mucoadhesive microspheres as a promising multiparticulate gastroretentive delivery system for enhancing the oral bioavailability of rosuvastatin calcium, with potential for dose reduction, improved tolerability, and enhanced therapeutic outcomes in the management of hypercholesterolemia.
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