During the formulation of solid dosage forms coating, plasticizers are added to the film forming polymer to improve the mechanical properties of the coating shell of the drug product. For the coating formulation to be successful and in order to produce flexible continuous film, the plasticizer should be compatible with the film forming polymer (i.e. high plasticizer-polymer miscibility in solid dispersion) (McGinity and Felton, 2008). This paper proposes and compares different multi-scale methods to predict the compatibility between plasticizers and film formers. The methods are based on, i) Molecule charge density using COSMO, ii) Solubility parameter calculation using Molecular dynamics, iii) Mesoscale simulation using DPD, where we propose a coarse-grain model, and iv) experimental DSC analysis for validation. The methods are tested for various blends including HPMC-PEG, MCC-PEG and PVP-PEG. The different methods showed similar results; PEG plasticizer diffuses inside HPMC and PVP polymer chains, thereby extending and softening the composite polymer. However, MCC surrounds PEG molecules without diffusing in its network, indicating low PEG-MCC compatibility. We also found that DPD simulations offer more details than the other methods on the miscibility between the compounds in aqueous solid dispersion, and can predict the amount of plasticizer that diffuse in the film forming polymer network.
- Molecular dynamics
- Pharmaceutical products