A computational-based approach to fabricate Ceritinib co-amorphous system using a novel co-former Rutin for bioavailability enhancement

Dani Lakshman Yarlagadda, Vullendula Sai Krishna Anand, Athira R. Nair, Swapnil J. Dengale, Sudharsan Pandiyan, Chetan H. Mehta, Suman Manandhar, Usha Y. Nayak, Krishnamurthy Bhat

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1 Citation (Scopus)

Abstract

In this study, we used molecular simulations to design Ceritinib (CRT) co-amorphous materials (CAMs) with concurrent improvement in solubility and bioavailability. Computational modeling enabled us to select the co-former by estimating the binding energy and intermolecular interactions. Rutin (RTH) was selected as a co-former for CRT CAMs using the solvent evaporation method to anticipate simultaneous improvement of solubility and bioavailability. The solid state characterization using DSC, XRPD, FT-IR, and a significant shift in Gordon Taylor experimental Tg values of co-amorphous materials revealed single amorphous phase formation and intermolecular interactions between CRT and RTH. The co-amorphous materials exhibited physical stability for up to 4 months under dry conditions (40 °C). Further, co-amorphous materials maintained the supersaturation for 24 hrs and improved solubility as well as dissolution of CRT. CRT:RTH 1:1 CAMs improved the permeability of CRT by 2 fold, estimated by employing the everted gut sac method. The solubility advantage of CAMs was also reflected in pharmacokinetic parameters, with a 3.1-fold and 2-fold improvement of CRT:RTH 2:1 in CRT exposure (AUC 0-t) and plasma concentration (Cmax) compared to the physical mixture, respectively.

Original languageEnglish
Pages (from-to)220-230
Number of pages11
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume190
DOIs
Publication statusPublished - 09-2023

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science

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