Silica-lipid hybrid (SLH) microcapsules: A novel oral delivery system for poorly soluble drugs

A silica-lipid hybrid (SLH) microcapsule system for oral delivery of poorly water-soluble drugs is reported for the first time. For the model drug celecoxib (CEL), SLH microcapsules composed of medium-chain triglycerides, lecithin and silica nanoparticles; with an internal porous matrix structure, w...

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Bibliographic Details
Published in:Journal of controlled release 2009-02, Vol.134 (1), p.62-70
Main Authors: Tan, Angel, Simovic, Spomenka, Davey, Andrew K., Rades, Thomas, Prestidge, Clive A.
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Biological and medical sciences
Biological Availability
Capsules - chemistry
Capsules - pharmacokinetics
Celecoxib
Drug Delivery Systems - methods
General pharmacology
In vitro dissolution
In vitro–in vivo correlation
In vivo pharmacokinetics
Lipid-based oral delivery
Lipids - chemistry
Male
Medical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Poorly soluble drugs
Pyrazoles - administration & dosage
Pyrazoles - chemistry
Pyrazoles - pharmacokinetics
Rats
Rats, Sprague-Dawley
Silicon Dioxide - chemistry
Solubility
Sulfonamides - administration & dosage
Sulfonamides - chemistry
Sulfonamides - pharmacokinetics
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Summary:A silica-lipid hybrid (SLH) microcapsule system for oral delivery of poorly water-soluble drugs is reported for the first time. For the model drug celecoxib (CEL), SLH microcapsules composed of medium-chain triglycerides, lecithin and silica nanoparticles; with an internal porous matrix structure, were shown to offer several physicochemical and biopharmaceutical advantages in comparison with unmodified drug, lipid emulsion, dry emulsion and the commercial product, Celebrex ®. DSC and XRD analyses confirmed non-crystalline CEL in SLH microcapsules and verified medium term physical stability. Dissolution under sink conditions revealed a 2- to 5-fold increase in dissolution efficiencies (%DE) and significantly reduced t 50% (≥ 50-fold) for CEL formulated as SLH microcapsules. Orally dosed in vivo studies in rats demonstrated superior pharmacokinetics for SLH microcapsules. Specifically, the fasted-state bioavailability ( F) was statistically higher ( p < 0.05) than for aqueous suspension, lipid solution, o/w emulsion and a maltodextrin-stabilised dry emulsion, and was greater than for Celebrex ®. SLHs showed the highest maximum plasma concentration ( C max) among all tested formulations ( p < 0.05). Linear correlations were observed between %DE and the pharmacokinetic parameters ( F and C max). It is postulated that SLH microcapsules improve CEL oral absorption via dissolution enhancement, potentially in conjunction with other unexplored mechanisms, hence offering the possibility of dose reduction for improved therapeutic efficacy and cost-effectiveness of poorly soluble drugs.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2008.10.014