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Complex hydrogels formed with chitosan (CS) and ring-opened polyvinyl pyrrolidone ( ro PVP) as a swellable mucoadhesive gastroretentive drug dosage form ( sm GRDDF) were prepared and characterized. CS/ ro PVP hydrogels were produced by blending CS with  ro PVP obtained by basic treatment of PVP. Effects of the heating time and NaOH concentration employed for preparing  ro PVP, and CS molecular weights (Mws), and  ro PVP/CS ratios on the swelling ability of the resultant hydrogels were characterized. Rheological characteristics were further examined. Results demonstrated that  ro PVP obtained in a 0.5 M NaOH solution heated to 50 °C for 4 h was suitable for producing complex hydrogels with CS. At a  ro PVP/CS ratio of 20:1, hydrogels composed of three different Mws of CS possessed optimal swelling and mucoadhesive abilities and rheological properties.  In vitro  dissolution revealed sustained drug release. A pharmacokinetic study exhibited that the plasma profile of alendronate followed a sustained manner with 3-fold enhancement of the oral bioavailability. In conclusion, the  sm GRDDF composed of CS/ ro PVP complex hydrogels was successfully developed and is potentially applicable to improve the clinical efficacy of bisphosphonates.

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Complex Hydrogels Composed of Chitosan with Ring-opened Polyvinyl Pyrrolidone as a Gastroretentive Drug Dosage Form to Enhance the Bioavailability of Bisphosphonates