Trichotomous gastric retention of amorphous capecitabine: An attempt to overcome pharmacokinetic gap

• Triple mechanism gastric retention owing to porous structure, swelling behavior and mucoadhesive nature.
• Sustained drug release due to utilization of cross linked xanthan and amorphous capecitabine.
• Thorough introspection into excipient selection.
• Novel ex-vivo mucoadhesion characterization using texture profile analyser.
• Upto fourfold elimination t1/2 prolongation of capecitabine in rodent model.

Capecitabine (CAP) is an oral drug of choice for treatment of colorectal cancer. But its short plasma half-life limits clinical utility and the usually prescribed dosing regimen results in significant periods of therapeutically irrelevant concentration. To overcome this pharmacokinetic void a trichotomous gastroretentive (TRGDDS) system made up of CAP housed in xanthan gum microparticles (CXGMP) has been developed for extending CAP's gastric residence time thereby prolonging the subsequent elimination. TRGDDS was evaluated for particle size (243 ± 25 μm), surface morphology (porous) entrapment efficiency (87.72 ± 7.31%), buoyancy (86.32 ± 2.3%), mucoadhesiveness (88 ± 4.3%), swelling index (80.37 ± 4.65). X-ray diffraction (XRD) and differential scanning calorimetry (DSC) of CXGMP suggested CAP had been rendered amorphous, a property which unconventionally slows its dissolution. Significant control was offered by CXGMP compared to crystalline CAP in terms of drug release. Pharmacokinetic studies in Wistar rat further revealed that CXGMP increased the MRT (three times), elimination half-life (roughly 4 fold) and AUC (1.44 folds) of CAP at a dose of 5 mg/kg in comparison to CAP solution of same strength. Conclusively the employment of TRGDDS had extended the duration for which CAP stayed in the rodent model, providing evidence for potentially obtaining a more efficacious dosing regimen in actual disease models.

Figure optionsDownload high-quality image (186 K)Download as PowerPoint slide