Development of novel L-sulpiride-loaded quaternary solid dispersion

Title
Development of novel L-sulpiride-loaded quaternary solid dispersion
Author
최종서
Advisor(s)
최한곤
Issue Date
2017-08
Publisher
한양대학교
Degree
Doctor
Abstract
ABSTRACT Development of novel L-sulpiride-loaded quaternary solid dispersion Part I : Comparison of L-sulpiride–loaded solvent–wetted and kneaded quaternary solid dispersion The purpose of this study was to compare the powder properties, solubility, dissolution and oral absorption of L-sulpiride–loaded solvent–wetted (SWQSD) and kneaded (KNQSD) quaternary solid dispersions. The SWQSD and KNQSD were prepared with silicon dioxide, sodium laurylsulfate and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) using a spray dryer and high shear mixer, respectively. Their powder properties, solubility, dissolution and oral absorption were assessed compared to L-sulpiride powder. The drug in SWQSD was in the amorphous state
however, in KNQSD, it existed in the crystalline state. The SWQSD with a drug/sodium laurylsulphate/TPGS/silicon dioxide ratio of 5/1/2/12 gave the higher drug solubility and dissolution compared to the KNQSD with the same composition. The oral absorption of drug in the SWQSD was 1.4 fold higher than the KNQSD and 3.0 fold higher than the L-sulpiride powder (p < 0.05) owing to better solubility and reduced crystallinity. Furthermore, the SWQSD at the half dose was bioequivalent of commercial L-sulpiride–loaded product in rats. Thus, the SWQSD with more improved oral absorption would be recommended as an alternative for the L-sulpiride–loaded oral administration. Key words: L-sulpiride
quaternary solid dispersion
solvent–wetted
kneaded
oral absorption   Part II : Effect of D-α-tocopheryl polyethylene glycol 1000 succinate on L-sulpiride–loaded solvent–evaporated quaternary solid dispersion The aim of this study was to assess the effect of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on the physicochemical characterization and oral bioavailability of novel L-sulpiride-loaded solvent–evaporated quaternary solid dispersion (SEQSD). The effect of carriers on drug solubility was investigated. Among the carriers tested, polyvinyl pyrrolidone (PVP), sodium lauryl sulfate (SLS) and TPGS were selected as a polymer, surfactant and absorption enhancer, respectively, due to their high drug solubility. Using the solvent evaporation method, numerous SEQSDs with different ratios of L-sulpiride, PVP, SLS and TPGS were prepared, and their physicochemical properties, solubility and release were evaluated. In addition, the influence of TPGS concentration on the oral bioavailability of various drug doses was evaluated. All SEQSDs converted the crystalline drug to the amorphous form and remarkably improved the solubility, release and oral bioavailability of the drug. Furthermore, the TPGS concentration in the SEQSDs hardly affected the crystallinity, particle size and release, but considerably increased the solubility and oral bioavailability of the drug. In particular, as the dose of administered drug was increased, TPGS provided a greater improvement in oral drug bioavailability. Thus, TPGS played an important role in improving the oral bioavailability of L-sulpiride. Moreover, the SEQSD with a drug/PVP/SLS/TPGS weight ratio of 5:12:1:20 with approximately 3.3-fold improved oral bioavailability would be recommended as a commercial pharmaceutical product for enhancing oral bioavailability of L-sulpiride. Key words: L-sulpiride
solvent-evaporated quaternary solid dispersion
D-α-tocopheryl polyethylene glycol 1000 succinate
oral absorption
administered drug dose
URI
http://dcollection.hanyang.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000102420http://hdl.handle.net/20.500.11754/33455
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > PHARMACY(약학과) > Theses (Master)
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