Investigating and Comparing the Applicability of the R3m Molecular Descriptor and Solubility Parameter Estimation Approaches in Predicting Dispersion Formation Potential of APIs in a Random Co-Polymer Polyvinylpyrrolidone Vinyl Acetate and its Homopolymer

Understanding the Influence of API Conformations on Amorphous Dispersion Formation Potential Predictions using the R3m Molecular Descriptor

“…The horizontal black dotted line indicates the R 3 m = 0.65 classification boundary published previously, , and the horizontal black dot-dashed line indicates the boundary updated using MD simulation results ( R 3 m = 0.632, see Figure ). Green boxes indicate API experimentally observed to successfully form ASDs in PVPVA, while those in red indicate compounds that failed to form ASDs. − …”

“…It was, therefore, necessary to first investigate whether conformational changes could result in any significant changes to R 3 m , and by extension, have a potential impact on future predictions of ASD formation in PVPVA made by the original R 3 m model . It is also noted that previous investigations of R 3 m in the context of dispersions formed via solvent-based cosolidification (e.g., spray-drying) have revealed that residual solvent can affect drug–polymer miscibility and, therefore, is likely to affect the conformations of API in the amorphous state. ,, For simplicity, therefore, only binary drug–PVPVA systems prepared via melt-quenching were considered here and extrapolation of the present findings to ASDs prepared using solvent-based methods should be done with caution.…”

“… 9 It is also noted that previous investigations of R 3 m in the context of dispersions formed via solvent-based cosolidification (e.g., spray-drying) have revealed that residual solvent can affect drug–polymer miscibility and, therefore, is likely to affect the conformations of API in the amorphous state. 7 , 8 , 10 For simplicity, therefore, only binary drug–PVPVA systems prepared via melt-quenching were considered here and extrapolation of the present findings to ASDs prepared using solvent-based methods should be done with caution.…”

“…In this paper, it was hypothesized that the distribution of R 3 m values captured by MD-simulated API conformations will be better predictors of dispersibility than a single conformation dictated by either that adopted in a crystal structure or gaseous state minimizations. Although a distribution of R 3 m for each molecule was expected to refine the classification boundary relative to its initial value, − this approach was expected to result in better estimations of the probability of dispersion formation in PVPVA. To address this hypothesis, the overall impact of 3D conformation on the value of R 3 m was investigated.…”

Solubility data and solubility parameters of barnidipine in different pure solvents

“…Table 5 summarizes the solvatochromic parameters,α, β, and π, as well as the Hansen solubility parameters of 15 solvents studied in this research taken from the literature. (28)(29)(30)(31)(32) Table 5. Solvatochromic parameters and total Hansen solubility parameter of some solvent studied.…”