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pH-independent controlled release tablets containing nanonizing valsartan solid dispersions for less variable bioavailability in humans
journal contribution
posted on 2018-08-01, 00:00 authored by J B Park, C Park, Z Z Piao, H H Amin, N M Meghani, Phuong TranPhuong Tran, T T D Tran, J H Cui, Q R Cao, E Oh, B J LeeThe aims of this work were to design pH-independent controlled release (CR) tablet containing nanonizing solid dispersion (SD) adsorbed on hydrophilic silica (Aeroperl®300/30). Valsartan (VAL) was chosen to simultaneously modulate solubility and release rate due to its poor water solubility in low pH condition and short elimination half-life. Based on extensive equilibrium solubility and compatibility studies, poloxamer 407 was selected as a SD carrier. The melted mixtures of drug and poloxamer 407 were adsorbed onto hydrophilic fumed silica (Aeroperl®300/30). Ternary SD system changed crystalline drug into an amorphous state and had intermolecular hydrogen bonding as confirmed by FT-IR with poloxamer 407. The dissolution rate of SD system was markedly enhanced as compared with pure VAL or commercial Diovan®tablet in simulated gastric fluid (pH 1.2). Interestingly, the particle size of SD system was gradually nanonized for 2 hr, ranging from 600 nm to 150 nm during dissolution process. The SD-loaded CR (SD-CR) tablets using hydroxypropylmethylcellulose (HPMC 4000) showed pH-independent zero-order release and good stability at accelerated conditions for six months. The SD-CR tablet showed minimized inter-subject variation of maximum plasma concentration as compared with commercial Diovan®tablets in healthy human volunteers.
History
Journal
Journal of drug delivery science and technologyVolume
46Pagination
365 - 377Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
ISSN
1773-2247Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2018, Elsevier B.V.Usage metrics
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No categories selectedKeywords
Nanonizing solid dispersionValsartanAdsorption CarrierEnhanced dissolutionpH-independent controlled releaseReliable human bioavailabilityScience & TechnologyLife Sciences & BiomedicinePharmacology & PharmacyLIPID-BILAYERSDRUG-DELIVERYHUMAN PLASMAWATERPHARMACOKINETICSSOLUBILITYTELMISARTANFORMULATIONVALIDATIONSTABILITY
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