Hot melt-extrusion improves the properties of cyclodextrin-based poly(pseudo)rotaxanes for transdermal formulation.

This study aimed to investigate whether hot-melt extrusion (HME) processing can modify the interactions between drugs, cyclodextrins and polymers, and in turn alter the microstructure and properties of supramolecular gels. Mixtures composed of amphiphilic polymer (Soluplus), cyclodextrin (HPβCD or αCD), plasticizer (PEG400 or PEG6000) and colloidal silicon dioxide were processed by HME. Carvedilol (CAR) was added to the formulation aiming its transdermal delivery. Extrudates were characterized by HPLC, XRPD, FTIR, DSC, and solid-state NMR. Gels prepared from extrudates (HME gels) or the corresponding physical mixtures (PM gels) in PBS were analyzed regarding components ordering (NMR, SEM), rheology, and CAR diffusion rate. HME led to the loss of the crystalline lattice of CAR and αCD, without causing any drug degradation. Solid NMR indicated that HME promoted the interaction of α-CD and HPβCD with the other components. HME gels had no coarsely disperse particles in their structure and behaved as weak gels (G' ~ G″). In contrast, PM gels contained drug crystals and showed elastic behavior (G' > G″). In general, HME gels were less viscous than PM ones and led to higher drug flux, especially those prepared using HPβCD. Moreover, the association of HPβCD and PEG6000 provided faster drug flux from supramolecular gels regardless the higher gel viscosity. The results evidenced that HME processing can decisively modify the arrangement of the components in the supramolecuar gels and, consequently, their properties, notably increasing drug release rate.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.