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

Document Type

Article

Abstract

Study Background: The research presented titled “A computational-based approach to fabricate Ceritinib co-amorphous system using a novel co-former Rutin for bioavailability enhancement” by Dani Lakshman Y, Sai Krishna Anand V, Athira R. Nair, Swapnil J D, Dr. Sudharshan P, Dr. Chetan H. M, Dr. Suman M, Dr. Usha Y. Nayak, and Dr. Krishnamurthy Bhat is centered on the fabrication of Ceritinib Co-amorphous systems (CAMs) using computational simulations. The prepared co-amorphous systems aim to improve Ceritinib's solubility, dissolution rate, stability, permeability, and bioavailability.

Research Goals and Hypotheses: The primary goal is to develop Ceritinib CAMs with a novel co-former, Rutin, which enhances the solubility and bioavailability of Ceritinib by stabilizing it in an amorphous form through intermolecular interactions.

Methodological Approach:

  1. Screening of co-formers based on the binding energy and intermolecular interactions with Ceritinib using Schrodinger software (Materials suite).
  2. Preparation of ceritinib co-amorphous systems with the selected co-former from simulations using quench cooling and solvent evaporation preparation techniques.
  3. The prepared co-amorphous systems were characterized by DSC, XRPD, and FTIR.
  4. The prepared co-amorphous systems were evaluated for in-vitro (solubility, dissolution), stability, moisture content, ex-vivo permeability, and in-vivo bioavailability.

Results and Discoveries:

  1. Rutin (RTH) was selected as a co-former due to the highest binding energy and intermolecular interactions with CRT. CRT CAMs were prepared using the solvent evaporation method.
  2. 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.
  3. The co-amorphous materials exhibited physical stability for up to 4 months under dry conditions (40 ⁰C). Further, co-amorphous materials maintained the supersaturation for 24 hrs and improved solubility as well as dissolution of CRT.
  4. 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.

Citation to the base paper: Yarlagadda, D. L., Sai Krishna Anand, V., Nair, A. R., Dengale, S. J., Pandiyan, S., Mehta, C. H., Manandhar, S., Nayak, U. Y., & Bhat, K. (2023). A computational-based approach to fabricate Ceritinib co-amorphous system using a novel co-former Rutin for bioavailability enhancement. European Journal of Pharmaceutics and Biopharmaceutics, 190(1), pp.220–230. https://doi.org/10.1016/j.ejpb.2023.07.019.

Publication Date

3rd August 2023

Recommended Citation

Yarlagadda, D. L., Sai Krishna Anand, V., Nair, A. R., Dengale, S. J., Pandiyan, S., Mehta, C. H., Manandhar, S., Nayak, U. Y., & Bhat, K, " A computational-based approach to fabricate Ceritinib co-amorphous system using a novel co-former Rutin for bioavailability enhancement " (2023). Open Access archive.

Publication Date

2023

Link to Full Text

Share

COinS