Theoretical and experimental investigation of drug-polymer interaction and miscibility and its impact on drug supersaturation in aqueous medium

Development of a Predictive Model for the Long-Term Stability Assessment of Drug-In-Adhesive Transdermal Films Using Polar Pressure-Sensitive Adhesives as Carrier/Matrix

“…There was a good agreement between experimental and calculated results using the DVS data. Besides, the predicted solubility values using water sorption data (equation (17) Flory-Huggins theory has also been used for ternary mixtures of API-polymer-water to determine the impact of RH on miscibility 8,10 , which only allowed a qualitative evaluation.…”

“…Different approaches for the prediction of drug crystallization in polymer matrix have already been described for solid dispersion applications only, based on thermodynamic [5][6][7][8][9][10] , kinetic 11 or a combination of thermodynamic and kinetic principles 12 . Typical semi-empirical thermodynamic approaches consisted in using thermal analysis (recrystallization of supersaturated solid dispersions or melting point depression methods) [6][7][8] , water sorption data 8,10 or solubility of API in low molecular weight analogue of polymer 7,8 , to apply either Flory-Huggins or the regular solution theory, which however do not allow for hydrogen bonding interactions.…”

“…Typical semi-empirical thermodynamic approaches consisted in using thermal analysis (recrystallization of supersaturated solid dispersions or melting point depression methods) [6][7][8] , water sorption data 8,10 or solubility of API in low molecular weight analogue of polymer 7,8 , to apply either Flory-Huggins or the regular solution theory, which however do not allow for hydrogen bonding interactions. Alternatively, Prudic et al 9 applied a computational thermodynamic model (PC-SAFT) to solve the water vapor-liquid and API solid-liquid equilibria to predict the impact of water sorption and API crystallization on API (indomethacin and naproxen) and polymer (PVP and poly(vinyl pyrrolidone-co-vinyl acetate)) solid dispersions.…”

Effects of Molecular Interactions on Miscibility and Mobility of Ibuprofen in Amorphous Solid Dispersions With Various Polymers

“…Unfortunately, literature summarized in a recent commentary62 indicates that the interaction parameter likely depends on many variables, including composition. For example, Baghel et al63 demonstrated a significant dependence of c drug-polymer on the weight fraction of cinnarizine in PVP, with interaction parameters varying from~À3 in 10% drug-PVP dispersions to nearly zero in 65% drug-PVP ASDs. The results in Figure 8 indicate that for IBP-PVP mixtures, where hydrogen bonding is extensive, c IBP-PVP changes significantly with the polymer concentration (i.e., decreasing with increasing % PVP at < 37% w/w PVP, staying roughly flat near 50% w/w PVP, then rising at > 69% w/w PVP).…”

Supersaturating drug delivery systems: The potential of co-amorphous drug formulations

“…When the mechanisms of precipitation inhibition are of interest, they can be studied experimentally by different approaches. For example, drug-inhibitor interactions are likely to stabilize the supersaturated state, if the drug and the inhibitor have been found to be miscible and interactions have been observed in the solid-state by Fourier-transform infrared spectroscopy (FTIR) or Raman spectroscopy (Baghel et al, 2016;Chauhan et al, 2013). Increasing ability to stabilize supersaturation by the increasing molecular weight of a polymer can indicate that increased solution viscosity may be the stabilizing mechanism, which can be evaluated by viscosity measurements (Miller et al, 2008).…”