In our previous study, polyvinylpyrrolidone (PVP) was used both as a binder
and a pore-former to prepare ethylcellulose (EC)-coated pellets to deliver topiramate
(TPM) for a controlled release profile. The objective of this work was to further optimize
the formulation and evaluate the in vivo profiles of TPM sustained-release pellets.
Similar to the previous formulation with no binder, the in vitro drug release of TPM
sustained-release pellets with 50% PVP binder in drug layer was sensitive to pore-former PVP level ranged from 27.0% to
29.0%. The higher the level of PVP was, the quicker release rate in vitro was. Moreover, when the proportion of poreformer
PVP decreased, the Cmax decreased, and the tmax and mean residence time of TPM coated pellets were both prolonged.
The in vitro release profile of optimal formulation showed biphasic release characteristics similar to reference
formulation Trokendi XR®, i.e., involving immediate release of TPM in initial release stage followed by a sustained release
up to 24 h. Moreover, the impact of the pH of release medium on the drug release rate of TPM sustained-release pellets
was not significant. The release mechanism of TPM from the sustained-release pellets might be the interaction of diffusion
(coating-film) and corrosion (drug layer). The in vivo pharmacokinetics results showed the TPM sustained-release
pellets had the similar in vivo pattern compared with Trokendi XR®. These studies provide valuable basis for further development
of TPM sustained-release pellets.
Keywords: Binder, In vivo pharmacokinetics, Pore-former, Sustained-release pellets, Topiramate.
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