Development and evaluation of zopiclone compression coated tablet for time-controlled pulse release

Early-morning awakening is a special insomnia characterized with circadian rhythm. In this study, zopiclone (ZOP), one of the common hypnotics, was selected to prepare zopiclone pulse release tablet via compression coating. Single-factor analysis combined with Box–Behnken design (BBD) was used to optimize the formulations.

Finally, ZOP compression coated tablets (CCTs) with burst release after a 2.5–3 h lag time (Tlag) were successfully obtained. A study of mechanical properties revealed that the generation of Tlag resulted from the break of the mechanical equilibrium between core swelling force and coating fracture strength, moreover, the time-varying curves of these two forces were both consistent with the Weibull distribution.

Compared with the commercial tablets, CCTs in beagle dogs showed a significant delay about 2.67 h which was similar to the Tlag in vitro. There was no significant difference in main pharmacokinetic parameters such as T1/2, AUC and Cmax. The relative bioavailability was 106.64%, indicating that Tlag of ZOP CCTs had no effect on the following pharmacokinetic process. Furthermore, a good in vivo-in vitro correlation (IVIVC) of ZOP CCTs was verified (R2 = 0.9625). The development of the ZOP CCTs provided a modified drug delivery system for early-morning awakening insomnia. Continue reading here