A novel elementary osmotic pump
tablet was developed. The system uses the core of
drug-resin complexes (DRCs) loaded with
propranolol hydrochloride (PNH) for time-controlled delivery. In traditional osmotic pump
tablets (OPTs), the lag time was always minimized. However, in the DRCs osmotic pump
tablet (DRCOPT), the lag time was increased to achieve the time-controlled delivery. The quantity of osmotic agent in the core and channeling agent in the coating
solution as well as
weight gain were confirmed to be essential for the release behavior. A spherical symmetric design was applied to the optimization of the DRCOPT. The optimal formulation mainly consisted of DRC 100 mg,
polyethyleneoxide (N80) 182 mg, and NaCl 30 mg. The ratio of
cellulose acetate (CA)/
polyethylene glycol 4000 was 15:3 (w/w) in coating
solution, and the
weight gain was 8%. The release behavior of the optimal DRCOPT was evaluated in media with different pH, rotation speeds, and ionic strength. It was found to generate a 2-h lag time, to deliver PNH at a rate of zero order from 2 h to 14 h in the medium of NaCl 0.15 mol/l, and the cumulative release at 24 h was 94%.
Drug relee was independent of pH and rotation speed, but was proportional to ionic strength. In summary, the lag time could be used in therapeutic regimens with the characteristics of
chronotherapy because of the lag time and provides a new concept for the development of osmotic pumps.