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Physical properties and in vivo bioavailability in human volunteers of isradipine using controlled release matrix tablet containing self-emulsifying solid dispersion

journal contribution
posted on 2013-06-25, 00:00 authored by Phuong TranPhuong Tran, Thao Truong-Dinh Tran, Zong Zhu Piao, Toi Van Vo, Jun Bom Park, Jisung Lim, Kyung Teak Oh, Yun-Seok Rhee, Beom-Jin Lee
Poorly water-soluble drug with a short half-life such as isradipine (IDP) offer challenges in the controlled release formulation because of low dissolution rate and poor bioavailability. Self-emulsifying solid dispersions (SESD) of IDP consisted of surfactant and fatty acid in poloxamer 407 (POX 407) as a carrier and were manufactured by the melting method. Then, controlled release HPMC matrix tablet containing SESD were prepared via direct compression. The dissolution behaviors and in vivo bioavailability of controlled release matrix tablet in healthy human volunteers were investigated. The physical properties of solid dispersion were also examined using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). It was shown that structure of IDP was amorphous in the solid dispersion. The dissolution rate of IDP from SESD was markedly enhanced because of increased solubility and wetting effect. Controlled release HPMC matrix tablets containing SESD released drug in a controlled manner and were stable during storage over 3 months at 40 °C/75% RH. Furthermore, the tablet containing 5mg IDP SESD showed significantly increased oral bioavailability and extended plasma concentration compared with the marketed 5 mg Dynacirc(®) capsule. A combined method of solid dispersion and controlled release technology could provide versatile dosage formulations containing IDP with poor water solubility and short half-life.

History

Journal

International journal of pharmaceutics

Volume

450

Issue

1-2

Pagination

79 - 86

Publisher

Elsevier

Location

Amsterdam, The Netherlands

ISSN

0378-5173

eISSN

1873-3476

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2013, Elsevier B.V.