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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 LeePoorly 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 pharmaceuticsVolume
450Issue
1-2Pagination
79 - 86Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
ISSN
0378-5173eISSN
1873-3476Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2013, Elsevier B.V.Usage metrics
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No categories selectedKeywords
AdultAntihypertensive AgentsBiological AvailabilityCalcium Channel BlockersCalorimetry, Differential ScanningDelayed-Action PreparationsExcipientsHumansIsradipineOleic AcidPolymersPowder DiffractionSilicon DioxideSolubilitySurface-Active AgentsTabletsX-Ray DiffractionYoung AdultScience & TechnologyLife Sciences & BiomedicinePharmacology & PharmacySelf-emulsifying solid dispersionEnhanced dissolutionControlled release tabletPhysicochemical propertiesIn vivo bioavailabilityWATER-SOLUBLE DRUGSORAL BIOAVAILABILITYHYDROPHILIC MATRIXBETA-CYCLODEXTRINCOMPRESSION FORCEPARTICLE-SIZEDISSOLUTIONSYSTEMSFORMULATION
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