Related Experiment Video
Updated: Jul 4, 2025

Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles
Published on: August 28, 2015
Elucidation of Molecular Interactions Between Drug-Polymer in Amorphous Solid Dispersion by a Computational Approach
Diah Lia Aulifa1, Adnan Aly Al Shofwan2, Sandra Megantara1
1Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia.
Introduction:
Amorphous drug dispersion is frequently used to enhance the solubility and dissolution of poorly water-soluble drugs, thereby improving their oral bioavailability. The dispersion of these drugs into polymer matrix can inhibit their recrystallization. The inter-molecular interactions between drug and polymer plays a role in the improvement of the dissolution rate, solubility, and physical stability of drug.
Aim:
This study aims to investigate the formation and interactions of ritonavir (RTV)/poloxamer (PLX) amorphous formulation using a computational approach via molecular dynamics (MD) simulations, which mimicked solvent evaporation and melt-quenching method.
Methods:
TheRoot Mean Square Deviation (RMSD) value, Root Mean Square Fluctuation (RMSF), Radial Distribution Function (RDF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA), and hydrogen bond interactions were analyzed to determine interaction mechanisms between RTV and PLX in amorphous solid dispersion.
Results:
The pi-alkyl bonds between RTV and PLX were formed after simulations of solvent evaporation, while the hydrogen bond interactions of RTV-PLX was observed during melt method simulations. These results indicate the successful formulation of amorphous solid dispersion (ASD) from RTV and PLX. The RMSD values obtained from the solvent evaporation, melt-cooling-A, melt-cooling-B, and melt-cooling-C methods were 3.33 Å, 1.97 Å, 1.30 Å, and 1.29 Å, respectively, while the average RMSF values were 2.65 Å, 1.04 Å, 1.05 Å, and 1.07 Å, respectively. This indicates that the suppression of translational motion of RTV from the melt method can be stronger than solvent evaporation caused by the intermolecular interactions of RTV-PLX.
Conclusion:
MD simulations helped in understanding the formation and interaction mechanisms of ASD formulations that were difficult to detect by experimental approaches.
More Related Videos
10:10Transport Properties of Ibuprofen Encapsulated in Cyclodextrin Nanosponge Hydrogels: A Proton HR-MAS NMR Spectroscopy Study
Published on: August 15, 2016
11:27A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Related Concept Videos
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Factors Influencing Drug Absorption: Pharmaceutical Parameters
Polymer Classification: Crystallinity
Crystalline domains are the regions where polymer chains are aligned in an orderly manner and held together in proximity by intermolecular forces. For example, chains in the crystalline domains of polyethylene and nylon are bound together by van der Waals...
Factors Influencing Drug Absorption: Drug Dissolution
Theories of Dissolution: The Danckwerts' Model and Interfacial Barrier Model
Factors Affecting Dissolution: Particle Size and Effective Surface Area