title: Physical properties and in vivo bioavailability in human volunteers of isradipine using controlled release matrix tablet containing self-emulsifying solid dispersion.
abstract: 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.
authors.affiliation: International University, Vietnam National University, Ho Chi Minh City, Viet Nam.
authors.forename: Phuong Ha-Lien
authors.initials: PH
authors.lastname: Tran
authors.forename: Thao Truong-Dinh
authors.initials: TT
authors.lastname: Tran
authors.forename: Zong Zhu
authors.initials: ZZ
authors.lastname: Piao
authors.forename: Toi Van
authors.initials: TV
authors.lastname: Vo
authors.forename: Jun Bom
authors.initials: JB
authors.lastname: Park
authors.forename: Jisung
authors.initials: J
authors.lastname: Lim
authors.forename: Kyung Teak
authors.initials: KT
authors.lastname: Oh
authors.forename: Yun-Seok
authors.initials: YS
authors.lastname: Rhee
authors.forename: Beom-Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics*; D005079:Excipients / Q000737:chemistry; D006801:Humans; D017275:Isradipine / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D019301:Oleic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D033362:Powder Diffraction; D012822:Silicon Dioxide / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013607:Tablets; D014961:X-Ray Diffraction; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D005079:Excipients; D011108:Polymers; D013501:Surface-Active Agents; D013607:Tablets; D019301:Oleic Acid; D012822:Silicon Dioxide; D017275:Isradipine