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

Pierre      Bon; Samer      Joudieh; Malika      Lahiani-Skiba; Frederic      Bounoure; Pierre      Dechelotte; Mohamed      Skiba

Abstract

The aim of this study was to evaluate the use of a β-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 β-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 α and β-cyclodextrins, or a β-cyclodextrin-based polymer associated to microcrystalline cellulose and 10 % (w/w) of nimesulide were compared. Yield between 800 and 1000 μm, 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 β-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 cyclodextrinbased 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 β-cyclodextrin-based polymer appears the most promising for testing in vivo bioavailability studies.

Keywords: Extrusion/spheronisation, Pellets, Cyclodextrins, Polymers of β-cyclodextrin, Nimesulide, Characterization, Dissolution

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