Freeze-dried crystalline dispersions: Solid-state, triboelectrification and simultaneous dissolution improvements

Abstract

The charging propensities of freeze-dried samples produced from combinations of Piroxicam (PXM) - a BCS Class II drug with d-glucosamine HCl (GLU) - a potential hydrophilic carrier were investigated in this study. Freeze-dried PXM:GLU solid dispersion samples were prepared at different PXM:GLU ratios and characterised using analytical techniques such as XRPD, DSC and SEM. In addition, the dissolution rate and triboelectric charging of the samples were investigated. DSC and XRPD results showed that the freeze-drying process produced crystalline materials which were mixtures of PXM polymorphs that included the monohydrate form. The dissolution rate of PXM was improved in the solid dispersions due to the presence of GLU compared to pure PXM with the freeze-dried PXM: GLU solid dispersion at the ratio of 1:1(500) showing the best improved dissolution of all the prepared samples. Electrostatics results showed PXM to have a higher tendency for charging in comparison to the carrier GLU (- 3.2 v 0.5 nC/g). Freeze-dried PXM:GLU showed an electropositive charging behaviour when the content of drug was ≤50% (w/w), whereas the freeze-dried samples containing >50% (w/w) of drug showed an opposite electronegative charging behaviour. The charge results also confirmed that GLU improved the handling of PXM through potential ordered mixture formations and shows how powder handling as well as dissolution can be manipulated to obtain the desired outcome.