Chitosan-Based Mucoadhesive Microspheres for Enhanced Oral Bioavailability of Lovastatin and Pravastatin: Formulation Optimization, In vitro Characterization, and In vivo Pharmacokinetic Evaluation (Research Article)

Author(s): Saritha Rasala and Mukesh Chandra Sharma

Abstract: Objective: This study aimed to develop and evaluate chitosan-based mucoadhesive microspheres as a gastroretentive drug delivery system to enhance the oral bioavailability of lovastatin (BCS Class II) and pravastatin sodium (BCS Class III). Methods: Mucoadhesive microspheres were prepared using the emulsion cross-linking method, with chitosan as the mucoadhesive polymer and glutaraldehyde as the cross-linker. The microspheres were characterized in terms of particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, ex vivo mucoadhesion, in vitro drug release, and in vivo pharmacokinetics in Wistar rats. Results: Optimized microspheres LM5 (lovastatin) and PM5 (pravastatin) (drug:chitosan ratio 1:3, glutaraldehyde 2.0 mL, stirring speed 750 rpm) exhibited mean particle sizes of 28.4±3.2 μm and 25.7±2.9 μm, respectively, with polydispersity index <0.25. Zeta potential values of +32.5±2.1 mV and +34.8±2.4 mV indicated good physical stability and electrostatic mucoadhesion potential, respectively. The entrapment efficiency was 78.3±2.5% (lovastatin) and 82.6±2.8% (pravastatin). Ex vivo mucoadhesion studies showed detachment forces of 0.48±0.06 N and 0.52±0.07 N, respectively, significantly higher than that of blank chitosan (0.35±0.04 N). Drug release followed Higuchi kinetics (R²=0.972 for LM5; R²=0.965 for PM5) with 78% and 86% release at 12 h, respectively. In vivo pharmacokinetic studies revealed a relative bioavailability of 582.9% for lovastatin and 293.5% for pravastatin compared to the control suspensions. Cmax increased from 48.3±5.2 ng/mL to 198.2±15.6 ng/mL for lovastatin and from 325.6±28.4 ng/mL to 618.4±51.2 ng/mL for pravastatin. Tmax was prolonged from 2.5 h to 5.0 h (lovastatin) and from 1.5 h to 4.5 h (pravastatin). Conclusion: Chitosan-based mucoadhesive microspheres significantly enhanced the oral bioavailability of both statins, outperforming other GRDDS approaches, and offering a promising platform for once-daily administration of cholesterol-lowering medications.

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