Study of Nanostructured Lipid Carriers (NLCs) and its Application in Transdermal Delivery System

• Main Authors: Yi-Shien Duh, 杜宜憲
• Other Authors: 林文貞
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/54421921991267113020

碩士 === 國立臺灣大學 === 藥學研究所 === 97 === The transdermal drug delivery system (TDDS) becomes more attractive in recent years by providing a convenient and safe drug administration route. For different drugs, it can further serve as functional roles in different purposes, for example, providing a localized and controlled drug delivery for NSAIDs without side effects on gastrointestinal tract; or a new way of acid-labile drugs’ administration to avoid from degradation in gastrointestinal tract or liver. The aim of this study is to develop dosage forms of indomethacin and lansoprazole with lipid nanoparticles and further discuss the application on TDDS. By using different lipid blends as the oil phase and various emulsification systems, we prepared different drug loaded solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), and determined their physical properties, such as thermal behavior, particle size, zeta-potential, and storage stability. Finally, we also examined the in vitro drug permeation and in vivo pharmacokinetic study of different dosage forms. As the results from differential scanning calorimetry and light spectrometer, the oil phase with a blend of Precirol ATO 5 and castor oil provides suitable physical properties for carrying indomethacin., and the storage stability can be further improved by combination of a crystallization inhibitor in the oil phase. The size of indomethacin loaded NLCs is around 200 nm, and zeta-potential is about -10 mV. Indomethacin loaded NLC provides a two-stage permeation behavior, and its drug permeation ability is lower than a commercial gel, which is benefit for treating chronic pain and inflammation. Particle size , zeta-potential and thermal behavior of the lansoprazole loaded NLCs are related with the compositions in different ratio of lipids or surfactants. Stearylamine can protect lansoprazole from degradation during the hot-melt emulsification process. The in vitro drug permeation behavior of lansoprazole loaded NLC and NLC enriched hydrogel are affected by the formulation compositions. Stearylamine in oil phase helps drug permeation; different permeation enhancers in hydrogel provide the best improvement on drug permeation with different concentrations. The in vivo pharmacokinetic study shows that NLC enriched hydrogel applied in rats’ skin provides a prolonged drug delivery rather than either intravenous bolus or oral administration, which makes an improvement of treating chronic gastroesophageal reflux disease.