Preparation and evaluation of bilayer-core osmotic pump tablets contained topiramate

PLoS One. 2022 Feb 25;17(2):e0264457. doi: 10.1371/journal.pone.0264457. eCollection 2022.

Abstract

Topiramate (TPM) was an antiepileptic agent commonly used in clinical. Studies showed that an oral preparation of TPM with extended-release manner could bring some benefits for epileptics. In this paper, controlled release push-pull osmotic pump (PPOP) tablets of sparingly water-soluble TPM were successfully prepared. This bi-layer tablet core mainly consisted of sodium chloride as osmotic promoting agent and polyethylene oxide as suspending and pushing agents. The influences of osmotic agents, pushing agents and the compositions of coating membrane on TPM release profiles were evaluated. An optimal formulation of TPM-PPOP was obtained through single-factor experiments. In vitro release tests showed that the optimum formulation could release TPM at an approximate zero-order rate up to 8 h. Pharmacokinetic behaviors of TPM-PPOP tablets were evaluated and compared with the immediate release capsules after an oral single dose in beagle dogs. Pharmacokinetics results demonstrated that the TPM-PPOP tablet was able to provide a prolonged release of TPM with longer tmax and mean residence time. Lower fluctuations of drug plasma levels could also be achieved with TPM-PPOP tablets. These results suggested that sparely water-soluble drugs as TPM can be designed to PPOP for efficacy and safety use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Availability
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Dogs
  • Drug Evaluation, Preclinical
  • Female
  • Male
  • Tablets
  • Topiramate* / pharmacokinetics
  • Topiramate* / pharmacology

Substances

  • Delayed-Action Preparations
  • Tablets
  • Topiramate

Grants and funding

NO - Initials of the authors Xiangyang Xie & Wen Lin received financial supports as followings: Natural Science Foundation of Hubei Province (Grant No. 2020CFB569), Health commission of Hubei Province scientific research projects (Grant No.WJ2021M218): Xiangyang Xie; Health commission of Hubei Province scientific research projects (Grant No. WJ2018H0116, WJ2019H422): Wen Lin. URL of each funder website: Natural Science Foundation of Hubei Province: https://jhsb.hbstd.gov.cn/main/index.jsp Health commission of Hubei Province scientific research project: https://wjw.hubei.gov.cn/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.