Release of a Poorly Soluble Drug from Cross-Linked β-Cyclodextrin-Based Polymer Pellets Prepared via Extrusion/Spheronisation

The aim of this study was to evaluate the use of a cyclodextrin-based polymer, and more exactly a highly crosslinked cyclodextrin-based polyester, as an excipient to accelerate the release of poorly soluble drugs from pellets obtained by extrusion-spheronisation. The cross-linked beta-cyclodextrin based polymer was associated to microcrystalline cellulose to facilitate the process of extrusion/spheronisation, and nimesulide was chosen as a poorly soluble model drug. Different formulations with natural and beta-cyclodextrins, or a beta-cyclodextrin-based polymer associated to microcrystalline cellulose and 10 % (w/w) of nimesulide were compared. Yield between 800 and 1000 m, pellets dimensions and surface morphology by scanning electron microscopy (SEM), Fourier Transform - Infrared Spectroscopy (FT-IR) spectra, disintegration and in-vitro drug release were evaluated. Due to pellet disintegration, accelerated dissolution of nimesulide was achieved with beta-cyclodextrin-based polymer, i.e. 75 +/- 2% in 120 min vs. 12 +/- 1% for pellets with only microcrystalline cellulose (p<0.05). On the other hand, pellets with the same percentage of cyclodextrins as cyclodextrin-based polymer, were not disintegrated, and the dissolution was limited around 35 +/- 1% after 120 min, with a release linked to the porosity enhancement by leaching of water soluble excipients. In conclusion, the formulations of nimesulide with cross-linked beta-cyclodextrin-based polymer appears the most promising for testing in vivo bioavailability studies.