Molecular simulation driven experiment for formulation of fixed dose combination of darunavir and ritonavir as anti-HIV nanosuspension

Mehta, Chetan Hasmukh and Narayan, Reema and Aithal, Gururaj and Dengale, Swapnil J and Shah, Abhishek and Nayak, Usha Yogendra (2019) Molecular simulation driven experiment for formulation of fixed dose combination of darunavir and ritonavir as anti-HIV nanosuspension. Journal of Molecular Liquids, 293. pp. 1-15. ISSN 0167-7322

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Abstract

In this study, we designed a fixed-dose combination (FDC) for Darunavir (DRV) and Ritonavir (RTV) using molecular simulations as a tool. Molecular modeling allowed us to choose the solvent and antisolvent required for the formation of nanosuspension by estimating the solubility parameter. Molecular dynamics simulations and the analysis of the same provided useful information at the molecular level. Hydrogen bonding interactions, radial distribution functions, the radius of gyration, diffusion coefficient, and density profile analysis allowed us to see the formation of particles virtually. With the information obtained from the simulations, we were able to design our experiments and found that the results from experiments complemented the findings from the simulations. Nanosuspension was prepared by using high-speed homogenization (HSH) followed by probe sonication. The solid-state characterization studies demonstrated that both the drugs remain in the amorphous form with absence of any intermolecular interactions. The pharmacokinetic study indicated a significant improvement in the oral bioavailability of DRV/RTV nanosuspension compared to the pure drug combination. Thus, the studies demonstrated that the developed FDC nanosuspension could be a useful alternative dosage form for treating human immunodeficiency virus (HIV) infected patients.

Item Type: Article
Uncontrolled Keywords: Nanosuspension ; Computational formulation approaches ; Molecular dynamics (MD) simulation ; High-speed homogenization (HSH) ; Probe sonication.
Subjects: Departments at MU > Public Health
Pharmacy > MCOPS Manipal > Pharmaceutical Quality Assurance
Pharmacy > MCOPS Manipal > Pharmaceutics
Pharmacy > MCOPS Manipal > Pharmacognosy
Depositing User: KMC Library
Date Deposited: 24 Jan 2020 14:01
Last Modified: 24 Jan 2020 14:01
URI: http://eprints.manipal.edu/id/eprint/154791

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