Prediction of drug-polymer miscibility through the use of solubility parameter based Flory-Huggins interaction parameter and the experimental validation: PEG as model polymer

• Published in: Journal of pharmaceutical sciences Vol. 102; no. 7; p. 2254
• Main Authors: Thakral, Seema, Thakral, Naveen K
• Format: Journal Article
• Language: English
• Published: United States 01-07-2013
• Subjects: Computer Simulation; Models, Chemical; Pharmaceutical Preparations - chemistry; Polyethylene Glycols - chemistry; Solubility; Thermodynamics
• ISSN: 1520-6017
• DOI: 10.1002/jps.23583

Important consideration for developing physically stable solid dispersion is miscibility of drug in carrier matrix. It is possible to predict thermodynamics of binary system through free energy calculations based on Flory-Huggins interaction parameter (χ(dp)). In present study, PEG 6000 as model polymer and dataset comprising commonly used drugs/excipients was selected. The three-dimensional solubility parameter based on group contribution method was utilized for systemic calculation of χ(dp) of the polymer with each compound in data set. On the basis of the values of χ(dp), it was possible to categorize all the compounds into three distinct categories, Types I and II: compounds predicted to be miscible and immiscible respectively with the polymer in all proportions and Type III: compounds expected to exhibit composition dependent miscibility behavior. The Bagley plot showed that majority of points for Type I fall in a region, which can approximately be delimited by a circle. Experimental verification through thermal analysis revealed that though it was possible to predict correctly miscibility behavior of Type II class compounds, distinction between Types I and III was less evident. Hence, solubility parameter based χ(dp) may be used as an initial tool for fast screening of immiscible combination of polymer and drug.