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Development of novel nanosuspension system for enhancing the oral bioavailability of celecoxib

Development of novel nanosuspension system for enhancing the oral bioavailability of celecoxib
Sung Chan Jeong
Issue Date
We aimed to develop a novel celecoxib (CXB)-loaded nanosuspension with improved dissolution and oral bioavailability. To achieve this, numerous CXBloaded nanosuspensions were prepared with various combinations of polymers and surfactants using a wet media milling process, and their particle sizes were determined. A 24 full factorial design was used to identify the most appropriate preparation conditions. The crystallinity, dissolution and oral bioavailability in rats of the CXB-loaded nanosuspensions were evaluated and compared with those of the drug powder and a commercial CXB-loaded product. Among the anosuspensions prepared with various polymers and surfactants, the nanosuspension prepared with copovidone and sodium laurylsulfate (SLS) gave the smallest particle size of drug. High agitator speed, longer milling time and high bead quantity decreased particle size, whereas large solution volume increased the particle size. In particular, the nanosuspension prepared with 5% (w/v) CXB, 4% copovidone and 0.1% SLS in distilled water using the wet media milling process at the preparing condition, such as agitator speed of 3000 rpm, milling time of 180 min, bead quantity of 550 g/batch and suspension quantity of 300 mL/batch, had the particle size of about 180 nm and physically stable 25°C at least for 8 weeks. It considerably improved the drug dissolution due to its reduced particle size. The plasma concentration, AUC and Cmax values in rats were significantly higher for the prepared CXB-loaded nanosuspension than those of the commercial capsule or drug powder. Thus, this novel CXB-loaded nanosuspension would be a promising candidate of with good physical stability and enhanced oral bioavailability.
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GRADUATE SCHOOL[S](대학원) > PHARMACY(약학과) > Theses (Ph.D.)
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