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QbD-Based Development of Cationic Self-nanoemulsifying Drug Delivery Systems of Paclitaxel with Improved Biopharmaceutical Attributes

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  • Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery
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Abstract

The present studies describe quality-by-design-based design and characterization of cationic self-nanoemulsifying formulations of paclitaxel for improving its biopharmaceutical attributes. Solubility and phase titration experiments were designed to select the lipidic and emulsifying excipients. Two different types of lipidic nanoformulations were developed using medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs). The nanoformulations were optimized by mixture designs and subjected to evaluation for globule size, zeta potential, drug release, and intestinal permeability. Following apt mathematical modeling, the optimum nanoformulation was earmarked using numerical optimization. Further, cationic formulations were developed for both LCT- and MCT-containing formulations and subjected to performance evaluation. The optimized formulations were extensively evaluated, where an in vitro drug release study indicated 2.7-fold improvement in dissolution rate from optimized cationic nanoformulations over powder pure drug. Ex vivo and in situ evaluation performed on Wistar rats exhibited nearly six- to eightfold enhancement in permeation and absorption parameters of the drug for the optimized cationic nanoformulation as compared to the pure paclitaxel. Pharmacokinetic studies indicated nearly 13.4-fold improvement in AUC and Cmax, along with 1.8-fold reduction in Tmax of the drug from cationic nanoformulations as compared to the pure drug suspension. Moreover, nanoformulation containing long-chain lipids exhibited superior performance (1.18-fold improvement in drug absorption) over medium-chain lipids. Cytotoxicity evaluation of cationic nanoformulations on MCF-7 cells revealed significant reduction in growth vis-à-vis the pure drug. Overall, the current paper reports successful systematic development of paclitaxel-loaded cationic self-nanoemulsifying systems with distinctly improved biopharmaceutical performance.

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Acknowledgments

The corresponding author gratefully acknowledges the generosity of M/s Stat-Ease Inc., Minneapolis, USA, for providing software support along with felicitation with “Stat-Ease QbD Performance Award 2014” for his exemplary contribution in the QbD-based drug delivery research.

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Authors and Affiliations

  1. UGC Centre of Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India

    Sarwar Beg, Ravinder Kaur, Rajneet Kaur Khurana, Teenu Sharma & Bhupinder Singh

  2. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India

    Sarwar Beg

  3. Pharmaceutics Division, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, 147002, India

    Vikas Rana

  4. UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh, 160014, India

    Bhupinder Singh

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  1. Sarwar Beg
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Correspondence to Bhupinder Singh.

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Beg, S., Kaur, R., Khurana, R.K. et al. QbD-Based Development of Cationic Self-nanoemulsifying Drug Delivery Systems of Paclitaxel with Improved Biopharmaceutical Attributes. AAPS PharmSciTech 20, 118 (2019). https://doi.org/10.1208/s12249-019-1319-x

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