Sustained-release of Cyclosporin A pellets: preparation, in vitro release, pharmacokinetic studies and in vitro-in vivo correlation in beagle dogs

The aim of this study was to develop Cyclosporin A (CsA) sustained-release pellets which could maintain CsA blood concentration within the therapeutic window throughout dosing interval and to investigate the in vitro-in vivo correlation (IVIVC) in beagle dogs. The CsA sustained-release pellets (CsA pellets) were prepared by a double coating method and characterized in vitro as well as in vivo. Consequently, the CsA pellets obtained were spherical in shape, with a desirable drug loading (7.18 +/- 0.17g/100g), good stability and showed a sustained-release effect. The C-max, T-max and AUC(0-24) of CsA pellets from the in vivo pharmacokinetics evaluation was 268.22 +/- 15.99ng/ml, 6 +/- 0h and 3205.00 +/- 149.55ngh/ml, respectively. Compared with Neoral (R), CsA pellets significantly prolonged the duration of action, reduced the peak blood concentration and could maintain a relatively high concentration level till 24h. The relative bioavailability of CsA pellets was 125.68 +/- 5.37% that of Neoral (R). Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the pellets. In conclusion, CsA pellets which could ensure a constant systemic blood concentration within the therapeutic window for 24h were prepared successfully. Meanwhile, this formulation possessed a good IVIVC.