A QbD Approach to Design and to Optimize the Self-Emulsifying Resveratrol-Phospholipid Complex to Enhance Drug Bioavailability through Lymphatic Transport

采用 QbD 方法设计和优化自乳化白藜芦醇-磷脂复合物,通过淋巴转运提高药物生物利用度

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作者:Syed Abul Layes Gausuzzaman, Mithun Saha, Shahid Jaman Dip, Shaiful Alam, Arup Kumar, Harinarayan Das, Shazid Md Sharker, Md Abdur Rashid, Mohsin Kazi, Hasan Mahmud Reza

Conclusions

This study suggests that an optimal self-emulsifying formulation can significantly increase the bioavailability of resveratrol through lymphatic transport to achieve the desired pharmacological effects.

Methods

The resveratrol−phospholipid complex (RPC) was formed by the solvent evaporation method and characterized by FTIR, DSC, and XRD analyses. The RPC-loaded self-emulsifying drug delivery system (SEDDS) was designed, developed, and optimized using the QbD approach with an emphasis on resveratrol transport through the intestinal lymphatic pathway. The in vivo pharmacokinetic study was investigated in male Wister Albino rats.

Results

The FTIR, DSC, and XRD analyses confirmed the RPC formation. The obtained design space provided robustness of prediction within the 95% prediction interval to meet the CQA specifications. An optimal formulation (desirability value of 7.24) provided Grade-A self-emulsion and exhibited a 48-fold bioavailability enhancement compared to the pure resveratrol. The cycloheximide-induced chylomicron flow blocking approach demonstrated that 91.14% of the systemically available resveratrol was transported through the intestinal lymphatic route. Conclusions: This study suggests that an optimal self-emulsifying formulation can significantly increase the bioavailability of resveratrol through lymphatic transport to achieve the desired pharmacological effects.

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