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Amalgamation of solid dispersion and melt adsorption techniques for augmentation of oral bioavailability of novel anticoagulant rivaroxaban

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Abstract

The objective of the present study was to evaluate the potential of solid dispersion adsorbate (SDA) to improve the solubility and bioavailability of rivaroxaban (RXN). SDA of RXN was developed by fusion method using PEG 4000 as carrier and Neusilin as adsorbent. A 32 full factorial design was utilized to formulate various SDAs. The selected independent variables were the amount of carrier (X1) and amount of adsorbent (X2). The responses measured were the time required for 85% drug release (Y1) and saturated solubility (Y2). MTT assay was employed for cytotoxicity studies on Caco-2 cells. In vivo pharmacokinetics and pharmacodynamic evaluations were carried out to assess the prepared SDA. Pre-compression evaluation of SDA suggests the prepared batches (B1–B9) possess adequate flow properties and could be used for compression of tablets. Differential scanning calorimetry and X-ray diffraction data signified the conversion of the crystalline form of drug to amorphous form, a key parameter accountable for improvement in drug dissolution. Optimization data suggests that the amount of carrier and amount of adsorbent significantly (P < 0.05) influence both dependent variables. Post-compression data signifies that the compressibility behavior of prepared tablets was within the official standard limits. A significant increase (P < 0.0001) in the in vitro dissolution characteristics of RXN was noticed in optimized SDA (> 85% in 10 min) as compared to the pure drug, marketed product, and directly compressible tablet. Cytotoxicity studies confirmed the nontoxicity of prepared RXN SDA tablets. RXN SDA tablets exhibited 2.79- and 1.85-fold higher AUC in comparison to RXN suspension and Xarelto tablets respectively indicating improved oral bioavailability. Higher bleeding time and percentage of platelet aggregation noticed with RXN SDA tablets in comparison to RXN suspension further substantiate the efficacy of the prepared formulation. In summary, the results showed the potential of RXN SDA tablets to enhance the bioavailability of RXN and hence can be an alternate approach of solid dosage form for its development for commercial application.

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All the data related to the manuscript has been included. The materials used in the experiments have been included in the “Materials and methods” section.

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Acknowledgements

The authors acknowledge the management of Maliba Pharmacy College, Bardoli, Surat, India for the support.

Funding

The funding for the research work was provided by Maliba Pharmacy College.

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Authors and Affiliations

  1. Maliba Pharmacy College, Uka Tarsadia University, Bardoli, Surat, 394350, India

    Pranav J. Shah, Milan P. Patel & Bhavin Vyas

  2. Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad, 382481, India

    Jigar Shah

  3. Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, 31982, Saudi Arabia

    Anroop B. Nair

  4. Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Sabna Kotta

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Contributions

Pranav J. Shah: Conceptualization, data curation, formal analysis, investigation, methodology, writing—review and editing. Patel Milan Pankajkumar: Conceptualization, data curation, formal analysis, investigation, methodology, writing—original draft preparation. Jigar Shah: Formal analysis, investigation, methodology, writing—review and editing. Sabna Kotta: Formal analysis, investigation, methodology, writing—review and editing. Anroop B. Nair: Formal analysis, investigation, methodology, writing—review and editing. Bhavin Vyas: Pharmacokinetic and pharmacodynamic studies, writing—review and editing.

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Shah, P.J., Patel, M.P., Shah, J. et al. Amalgamation of solid dispersion and melt adsorption techniques for augmentation of oral bioavailability of novel anticoagulant rivaroxaban. Drug Deliv. and Transl. Res. 12, 3029–3046 (2022). https://doi.org/10.1007/s13346-022-01168-9

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