A time-released osmotic pump fabricated by compression-coated method: Formulation screen, mechanism research and pharmacokinetic study

In this investigation, time-released monolithic osmotic pump (TMOP) tablets containing diltiazem hydrochloride (DIL) were prepared on the basis of osmotic pumping mechanism. The developed dosage forms were coated by Kollidon®SR-Polyethylene Glycol (PEG) mixtures via compression-coated technology instead of spray-coating method to form the outer membrane. For more efficient formulation screening, a three-factor five-level central composite design (CCD) was introduced to explore the optimal TMOP formulation during the experiments. The in vitro tests showed that the optimized formulation of DIL-loaded TMOP had a lag time of 4 h and a following 20-h drug release at an approximate zero-order rate. Moreover, the release mechanism was proven based on osmotic pressure and its profile could be well simulated by a dynamic equation. After oral administration by beagle dogs, the comparison of parameters with the TMOP tablets and reference preparations show no significant differences for Cmax (111.56 ± 20.42, 128.38 ± 29.46 ng/ml) and AUC0-48 h (1654.97 ± 283.77, 1625.10 ± 313.58 ng h/ml) but show significant differences for Tmax (13.00 ± 1.16, 4.00 ± 0.82 h). These pharmacokinetic parameters were consistent with the dissolution tests that the TMOP tablets had turned out to prolong the lag time of DIL release.