The aim of the research was to investigate three “critical steps” that deserve particular attention during the mechanochemical activation of vincamine. The first step consisted in the selection of the best polymeric carrier/most affine stabiliser between linear PVP and NaCMC by using the GRID and the GRID based AutoDock software packages which permit to calculate their surface features and interactions. Moreover, the calculation of the partial and total solubility parameters supported the results obtained by GRID and AutoDock software.
Then, after the selection of linear PVP-K30 as the suitable carrier, the influence of process and formulation variables on the amorphisation degree and solubility enhancement was studied, to select the most suitable process conditions and formulation parameters. Subsequently, the best performing samples were widely characterised using XRPD, TEM and SSNMR (including the proton relaxation (1H T1 NMR) time) techniques. These studies highlighted that all the coground samples were nanocrystalline solid dispersions indicating a dramatic difference between the amorphisation capacities of linear PVP-K30 and cross-linked PVP, used in previous analogous experiences. In particular, 13C, 15N and 1H T1 NMR data point to a description of the system as a dispersion of nanocrystals in the polymer. In these dispersions vincamine is in a disordered crystalline state due to extensive interactions and contacts with PVP-K30 but the main hydrogen bonding motif characterising its packing remains. Again, differently from cross-linked PVP, dissolution studies revealed that linear PVP-K30 was able to promote a complete in vitro solubilisation of vincamine in some coground samples. What is more important, by using a linear polymer, drug-to-polymer and milling time variables appeared less influent on the solid state and in vitro properties of the composites. Finally, stability studies conducted for a period of 1 year highlighted the high physical stability of the selected samples.