Cyclodextrin-based poly(pseudo)rotaxanes for transdermal delivery of carvedilol.

ABSTRACT

This work aimed to design supramolecular gels combining Soluplus or Solutol and alfa- and hydroxypropyl-ß-cyclodextrin (α-CD, HPß-CD) for carvedilol (CAR) transdermal delivery. Poly(pseudo)rotaxane formation (appearance, SEM, 1H NMR), drug solubilization, rheological properties and in vitro release were investigated. CAR-CD complexes were prepared in situ or by spray drying. For Solutol, poly(pseudo)rotaxanes were formed immediately after mixing with α-CD and did not influence CAR solubility. Differently, Soluplus poly(pseudo)rotaxanes took 24-48 h to be formed and CAR solubility decreased compared to Soluplus micelles. Soluplus 20% + α-CD (5-10%) showed higher G' and G'' but also faster CAR release than Solutol poly(pseudo)rotaxanes, which is explained by the different location of PEG chains in the two amphiphilic polymers. Faster drug release was achieved incorporating HPß-CD or CAR-HPß-CD spray-dried complexes. The results evidenced the versatility of the formulations in terms of rheological behavior and drug release patterns, which can be adjusted for CAR transdermal delivery.