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

Yuan Zeng,Xiangyang Xie,Qiongzhi Shi,Hui Liu,Vineet Kumar Rai,Yinke Li,Xiangru Liao,Wei Tian,Wen Lin

doi:10.1371/journal.pone.0264457

Yuan Zeng, Xiangyang Xie + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0264457

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Journal: PloS one	Publication Date: Feb 25, 2022
Citations: 3	License type: CC BY 4.0

Affiliation: Central Hospital of Wuhan, Huangshi Central Hospital

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.

Highlights

Topiramate (TPM; 2,3:4,5-Di-O-isopropylidene-β-D-fructopyranose sulfamate), an antiepileptic agent, is commonly used in clinical as a monotherapy or adjunctive therapy for patients with partial onset seizures, or primary generalized tonic-clonic seizures [1, 2]
In order to study the influence of polyethylene oxide (PEO) molecular weight (Mw) in drug layer on the drug release profile, PEOs with various Mws were investigated
The results demonstrated that the gastrointestinal fluid scarcely affected TPM release, for the f2 among them were all larger than 50 (f2: simulated gastric fluid (SGF)-simulated intestinal fluid (SIF): 85.1; SIF-simulated colonic fluid (SCF): 75.4; SGF-SCF: 70.9)

Summary

Introduction

Topiramate (TPM; 2,3:4,5-Di-O-isopropylidene-β-D-fructopyranose sulfamate), an antiepileptic agent, is commonly used in clinical as a monotherapy or adjunctive therapy for patients with partial onset seizures, or primary generalized tonic-clonic seizures [1, 2]. In late 2012, TPM was approved by the United States Food and Drug Administration (FDA) in combination with phentermine for weight loss [3]. The conventional dosage form of TPM (Topamax1) is a capsule with immediate release beads in it [2]. TPM has a relatively long half-life of 21 h in vivo, it has not been prescribed as a single dose, partially due to severe adverse effects that often result with peak plasma levels of the drug when taken in high doses [4]. The side effects and poor adherence of immediate release TPM is hindering the epileptics from keeping seizure free.

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