Development of a Novel Controlled-Release Tablet of Pregabalin: Formulation Variation and Pharmacokinetics in Dogs and Humans

Abstract

Background

Novel three-layered (TL) tablet systems were compared with both monolithic matrix (MM) formulations and a commercial immediate-release (IR) capsule to develop once-a-day (OAD) pregabalin tablets.

Methods

The physical properties of the TL tablets, including dissolution and swelling rates, were compared with those of the MM tablets and the pharmacokinetic parameters of the TL tablet were compared with those of an IR capsule in beagles and humans.

Results

Our results indicated that the same amount of a hydrophilic polymer in the formulations had similar dissolution profiles at 12 h, regardless of the tablet geometry. However, the degree of tablet swelling differed, with larger amounts of polymer in the tablets showing a greater degree of swelling. In addition, TL tablets swelled more rapidly compared with MM tablets. For the pharmacokinetic study of the TL tablet, the beagles demonstrated absorption results similar to those of an IR capsule, whereas the humans demonstrated low total absorption compared with an IR capsule. The time of the peak plasma concentration at 6 h in the fed state of humans coincided with the results of the study on beagles.

Conclusion

The novel TL tablet system of pregabalin may prove to be helpful in developing improved formulations with better continuous drug absorption for OAD administration.

Keywords:

• controlled-release
• three-layered tablet
• polyethylene oxide
• high swellable
• once-a-day

Data Sharing Statement

The raw data of this study will not be shared because of confidentiality.

Disclosure

Kyung Hun Kim, Seo Hyun Lim, Cho Rok Shim, Junsung Park, Woo Heon Song, Min Chang Kwon, Jun Sang Park report grants from Ministry of Trade, Industry and Energy, Republic of Korea, during the conduct of the study. These authors have patents KR102039344B1 and KR102039345B1 registered to GL PharmTech. Jong Hyuk Lee and Han-Gon Choi has nothing to disclose. The authors report no other conflicts of interest in this work.