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Amalgamation of Solid Dispersion and Melt Adsorption Technique: Improved In Vitro and In Vivo Performance of Ticagrelor Tablets

  • Research Article
  • Theme: Advancements in Amorphous Solid Dispersions to Improve Bioavailability
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Abstract

Ticagrelor (TG) suffers from low peroral bioabsorption (36%) due to P-gp efflux and poor solubility (10 µg/mL). TG solid dispersion adsorbates (TG-SDAs) were formulated using an amalgamation of solid dispersion and melt adsorption techniques which were simple, economic, scalable, and solvent-free. FTIR indicated no incompatibility between drug and excipients. DSC, XRD, and SEM suggested a reduction in TG crystallinity. Q30min from TG-SUSP and TG-conventional tablets was only 2.30% and 6.59% respectively whereas TG-SDA-based tablets exhibited a significantly higher drug release of 86.47%. Caco-2 permeability studies showed 3.83-fold higher permeability of TG from TG-SDAs. TG-SDA-based tablets exhibited relative bioavailability of 748.53% and 153.43% compared to TG-SUSP and TG-conventional tablets respectively in rats. TG-SDA-based tablets were devoid of any cytotoxicity as indicated by MTT assay and exhibited better antiplatelet activity in rats. Enhanced oral bioavailability of TG-SDAs can be attributed to inhibition of P-gp efflux by PEG 4000, increased wettability, and reduced crystallinity of drug leading to improved drug solubility and dissolution. Improved bioabsorption results in a reduction of dose, cost of therapy as well as dose-related side effects. Thus, SDAs can be considered a promising and scalable approach for the improvement of dissolution rate and solubility of TG. TG-SDAs can be translated to an effective and safe dosage form, whereby its rapid onset of action promotes the prevention of heart attack, stroke, and related ill events in individuals with the acute coronary syndrome. However, scale-up, validation, and clinical-studies are necessary for confirmation of the proof-of-concept.

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Funding

This study is funded by the Maliba Pharmacy College.

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Authors and Affiliations

  1. Maliba Pharmacy College, Uka Tarsadia University, Maliba Campus, Gopal Vidyanagar, Bardoli-Mahuva Road, At & Po: Tarsadi-394350, Dist: Surat, Gujrat, India

    Mukesh Yadav, Jayant Sarolia, Bhavin Vyas & Pranav Shah

  2. Babaria Institute of Pharmacy, BITS Edu Campus, Varnama, Vadodara, India

    Manisha Lalan

  3. Priyadarshini J. L. College of Pharmacy, MIDC, Hingna Road, Nagpur, MS, India, 440016

    Shubhada Mangrulkar

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  1. Mukesh Yadav
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  2. Jayant Sarolia
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  4. Manisha Lalan
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  5. Shubhada Mangrulkar
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  6. Pranav Shah
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Contributions

Mukesh Yadav: data collection; Jayant Sarolia: data collection; Manisha Lalan: draft manuscript preparation; Shubhada Mangrulkar Bhavin Vyas: analysis and interpretation of results; Bhavin Vyas: study conception and design; Pranav Shah: study conception and design. All the authors reviewed the results and approved the final version of the manuscript.

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Correspondence to Pranav Shah.

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Yadav, M., Sarolia, J., Vyas, B. et al. Amalgamation of Solid Dispersion and Melt Adsorption Technique: Improved In Vitro and In Vivo Performance of Ticagrelor Tablets. AAPS PharmSciTech 22, 257 (2021). https://doi.org/10.1208/s12249-021-02138-z

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