Pharmacokinetic and pharmacodynamic evaluation of a new sustained-release capsules using starch-sponge matrix (SSM) release system for nifedipine in rats

Asako Nishimura, Kazumasa Naruhashi, Yu Yamamoto, Mami Hamori, Keiko Tabata, Keiko Seto, Nobuhito Shibata

Abstract


We conducted a performance assessment study for a new sustained-release capsule including starch-sponge matrix (SSM). The SSM, which is a support medium for drug release, was made from 2.5% cornstarch glue by means of freezing dry method. The SSM capsule was applied for nifedipine (NFP), a calcium channel blocker, and evaluated pharmacokinetic and pharmacodynamic (PK/PD) profiles of NFP after intraduodenal administration of SSM capsules including 2.5 or 5.0 mg of NFP per capsule to rats. Plasma NFP concentrations from the SSM capsules showed dose-dependent increases with a Michaelis-Menten like behavior over 360 minutes after intraduodenal administration. The values of area under the concentration vs. time curve from time zero to 360 min (AUC0-360) of NFP declined in making SSM capsules as compared to control capsules due to a simple physical mixture of NFP and cornstarch, but the values of mean residence time (MRT0-360) extended and abidingness of SSM capsules were admitted with dose-dependent manner. As for a PD parameter, the mean arterial blood pressure (mABP) derived from the SSM capsules showed 15~20% decrease of baseline within 120min after intraduodenal administration, and thereafter the mABP in 2.5 mg SSM capsule was gradually recovered, while a relatively smooth and even change was found in the mABP at 5.0 mg SSM capsule. The relationships between plasma NFP concentration and sampling-time corresponding mABP after intraduodenal administration of SSM capsules showed no rapid change in the mABP, indicating that a sustained-release mechanism due to the SSM functions sufficiently to avoid a fluctuating blood pressure accompanied by going up and down of plasma levels of NFP. The SSM capsules exhibited a sustained-release pharmacokinetics of NFP, and made the fluctuation range with blood pressure small compared to the physical mixture preparations. Thus, it was evidenced that the SSM capsule is useful device to provide a sustained-release systems and optimal therapeutic efficacy of drugs.

Keywords: Controlled-release, Cornstarch, Matrix, Nifedipine, Pharmacokinetics, Pharmacodynamics.


Keywords


Controlled-release, Cornstarch, Matrix, Nifedipine, Pharmacokinetics, Pharmacodynamics.

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