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Articles by Kit-Lam Chan
Total Records ( 1 ) for Kit-Lam Chan
  Hai-Qiu Ma , Bin-Seng Low , Kit-Lam Chan and Nurzalina Abdul Karim Khan
  Background: Phyltetralin (1) and phyllanthin (2) are two potent anti-hyperuricemic lignans in the standardized Phyllanthus niruri extract (PNF5) yet displayed low oral bioavailability in rats. Objective: The purposes of the current study were to investigate the contributing factors towards the poor bioavailabilities of the lignans in PNF5 and increase the bioavailability by developing a formulation method, which can specifically overcome these contributing factors. Materials and Methods: Aqueous solubility, pH stability, P-glycoproteins efflux and first-pass metabolism of 1 and 2 in PNF5 were evaluated accordingly using in vitro methods. The PNF5 was subsequently formulated as Gelucire®44/14-based solid dispersion capsules (PNF5-SDC) and the oral bioavailabilities of 1 and 2 in PNF5-SDC were estimated compared to that of the conventional PNF5 powder filled capsules (PNF5-PFC). Results: The study shown that the solubility of PNF5 was 0.12±0.02 mg mL–1, pH value of GIT lumen were not significant affected the lignans absorption (p>0.05). The in vitro absorption of lignans significantly improved by combination with P-glycoprotein inhibitors: Verapamil (p<0.001) and quinidine (p<0.05). In addition, there were no significant variation for the amount of 1 (p = 0.4363) and 2 (p = 0.5396) and no metabolites were observed when PNF5 incubated with homogenized liver. Moreover, the relative oral bioavailability of the lignans in PNF5-SDC was increased by 3 fold (p<0.05), higher than those in PNF5-PFC when orally administered in rats. Conclusion: The results suggest that the poor bioavailability of 1 and 2 was due mainly to its poor aqueous solubility and P-glycoprotein (P-gp) efflux. Gelucire®44/14-based solid dispersion could significant improve the bioavailability of lignans.
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