Molecular modeling as a predictive tool for the development of solid dispersions.
In this study molecular modeling is introduced as a novel approach for the development of pharmaceutical solid dispersions. A computational model based on quantum mechanical (QM) calculations was used to predict the miscibility of various drugs in various polymers by predicting the binding strength between the drug and dimeric form of the polymer. The drug/polymer miscibility was also estimated by using traditional approaches such as Van Krevelen/Hoftyzer and Bagley solubility parameters or Flory-Huggins interaction parameter in comparison to the molecular modeling approach. The molecular modeling studies predicted successfully the drug-polymer binding energies and the preferable site of interaction between the functional groups. The drug-polymer miscibility and the physical state of bulk materials, physical mixtures, and solid dispersions were determined by thermal analysis (DSC/MTDSC) and X-ray diffraction. The produced solid dispersions were analyzed by X-ray photoelectron spectroscopy (XPS), which confirmed not only the exact type of the intermolecular interactions between the drug-polymer functional groups but also the binding strength by estimating the N coefficient values. The findings demonstrate that QM-based molecular modeling is a powerful tool to predict the strength and type of intermolecular interactions in a range of drug/polymeric systems for the development of solid dispersions.
†Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich, Medway Campus, Central Avenue, Chatham Maritime, Chatham, Kent ME4 4TB, U.K.
Mohammed
M
Maniruzzaman
†Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich, Medway Campus, Central Avenue, Chatham Maritime, Chatham, Kent ME4 4TB, U.K.
Jiayun
J
Pang
‡Cardiff Catalysis Institute, School of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, U.K.
David J
DJ
Morgan
†Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and Science, University of Greenwich, Medway Campus, Central Avenue, Chatham Maritime, Chatham, Kent ME4 4TB, U.K.
Dennis
D
Douroumis
D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D019281:Dimerization; D004339:Drug Compounding / Q000379:methods; D015195:Drug Design; D004355:Drug Stability; D006358:Hot Temperature; D008956:Models, Chemical; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry; D056951:Photoelectron Spectroscopy; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D011789:Quantum Theory; D012995:Solubility; D013816:Thermodynamics; D014961:X-Ray Diffraction
D004364:Pharmaceutical Preparations; D011108:Polymers
drug−polymer interactions; miscibility; molecular modeling; quantum mechanics; solid dispersions