TY - JOUR
T1 - A computational-based approach to fabricate Ceritinib co-amorphous system using a novel co-former Rutin for bioavailability enhancement
AU - Yarlagadda, Dani Lakshman
AU - Anand, Vullendula Sai Krishna
AU - Nair, Athira R.
AU - Dengale, Swapnil J.
AU - Pandiyan, Sudharsan
AU - Mehta, Chetan H.
AU - Manandhar, Suman
AU - Nayak, Usha Y.
AU - Bhat, Krishnamurthy
N1 - Funding Information:
The authors would like to acknowledge MSN laboratories Private Limited for providing a gift sample of the drug. We sincerely thank the Science and Engineering Research Board, Dept. of Science and Technology, New Delhi, India (Ref. No. EMR/2016/007006) for supporting this work by providing the grant for the infrastructure facility to carry out computational studies. Further, Saikumar Matcha is also acknowledged for his help in analyzing pharmacokinetic data.
Funding Information:
Dani Lakshman Yarlagadda is grateful to the Manipal Academy of Higher Education (MAHE) for providing Dr. TMA Pai Fellowship and Intramural funding (IMF) for the perusal of Doctoral studies at Manipal College of Pharmaceutical Sciences.
Funding Information:
The authors would like to acknowledge MSN laboratories Private Limited for providing a gift sample of the drug. We sincerely thank the Science and Engineering Research Board, Dept. of Science and Technology, New Delhi, India (Ref. No. EMR/2016/007006) for supporting this work by providing the grant for the infrastructure facility to carry out computational studies. Further, Saikumar Matcha is also acknowledged for his help in analyzing pharmacokinetic data. Dani Lakshman Yarlagadda is grateful to the Manipal Academy of Higher Education (MAHE) for providing Dr. TMA Pai Fellowship and Intramural funding (IMF) for the perusal of Doctoral studies at Manipal College of Pharmaceutical Sciences.
Publisher Copyright:
© 2023
PY - 2023/9
Y1 - 2023/9
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85168807965
UR - https://www.scopus.com/pages/publications/85168807965#tab=citedBy
U2 - 10.1016/j.ejpb.2023.07.019
DO - 10.1016/j.ejpb.2023.07.019
M3 - Article
C2 - 37524214
AN - SCOPUS:85168807965
SN - 0939-6411
VL - 190
SP - 220
EP - 230
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -