Evaluation of Predictive Models for Stable Solid Solution Formation

Solubility parameter-based screening methods for early-stage formulation development of itraconazole amorphous solid dispersions

“…Recently, a new GC parameter set, specifically designed by Just et al ., to predict the compatibility of solid drug and polymer has shown an improved predictive power, relative to previously used GC parameter sets . In this study, the GC methods developed by Van Krevelen/Hoftyzer and Hoy were used with this extended parameter set developed by Just et al . The former are well‐established GC methods used in a variety of scientific fields, the latter being specifically developed for HME applications.…”

“…Comparison of δ and related differences calculated through different GC methods should be performed carefully, ideally by relating δ values estimated using the same approach. The selection of Soluplus, VA64, 17PF and EPO derived from the evaluation of Δδ values was mainly influenced by the difference in drug–excipient interactions, mainly hydrogen bonding . Δδ provides a sensitive tool for discriminating polymers based on a more accurate evaluation of polar, dispersive and hydrogen bonding forces.…”

“…In general, a decreasing T m onset was observed as the concentration of excipient increased (Figure ). To investigate the extent of the solubility of the crystalline drug in the polymeric carrier, the reduction of fusion enthalpy of pure itz was compared with that obtained for PMs, adjusting for drug dilution effects . The melting enthalpy (ΔH PM) and onset T m of PMs were correlated with the fusion enthalpy (ΔH itz) and onset T m of pure drug, respectively.…”

“…With regard to producing amorphous solid dispersions using HME, theoretical and practical screening approaches have been developed to identify a rank order of miscibility within drug–excipient systems. The application of group contribution (GC) methods allows the calculation of solubility parameters (δ) of drugs and excipients and the prediction of their compatibility . The δ, originally defined by Hildebrand as the square root of the cohesive energy density (CED) of the molecule in the amorphous state, was employed to correlate the order of solubility of non‐electrolytes in non‐polar organic solvents at room temperature .…”

“…A rapid experimental approach to investigate the miscibility of drug–polymer blends may be achieved using differential scanning calorimetry (DSC), where T m onset and heat of fusion of the crystalline drug can be examined on the first heating scan . Miscible drug–polymer systems present depression of the T m relative to that of the pure drug.…”