International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2017.11.21Phyllanthus niruri Solid Dispersion: A Potential Alternative Gout Therapy]]>MaHai-Qiu LowBin-Seng ChanKit-Lam KhanNurzalina Abdul Karim 12017131Background: 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 mL1, 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.]]>Baker, J.F. and H.R. Schumacher,201064371377Rock, K.L., H. Kataoka and J.J. Lai,201391323Lin, K.C., H.Y. Lin and P. Chou,20002715011505Khoo, B.P. and Y.H. Leow,200041156160Murugaiyah, V. and K.L. Chan,2006Phyllanthus niruri.]]>7212621267Yeo, S.C.M., P.C. Ho and H.S. Lin,20135710151025Constantinides, P.P. and K.M. Wasan,2007In vitro/in vivo case studies.]]>96235248Kwan, K.C.,19972513291336Yuksel, N., A. Karatas, Y. Ozkan, A. Savaser, S.A. Ozkan and T. Baykara,2003In vitro and in vivo evaluation.]]>56453459Jannin, V., J. Musakhanian and D. Marchaud,200860734746Murugaiyah, V. and K.L. Chan,2007Phyllanthus niruri L. by a simple high-performance liquid chromatography method with fluorescence detection.]]>1154198204Low, B.S., C.H. Teh, K.H. Yuen and K.L. Chan,2011Eurycoma longifolia extract (Fr 2) on the bioavailability and pharmacokinetic properties and their implications for oral antimalarial activity.]]>6337341Barthe, L., M. Bessouet, J.F. Woodley and G. Houin,1998173255258Ma, H.Q., F. Ebrahimi, N.A.K. Khan and K.L. Chan,2015Eurycoma longifolia quassinoids in lipid-based solid dispersion.]]>2015Wilson, T.H. and G. Wiseman,1954Mesocricetus auratus).]]>123126130Sawyer, R.T.,1988in situ hepatic trapping of Candida albicans.]]>1048185Venishetty, V.K., N. Parikh, R. Sistla, F.J. Ahmed and P.V. Diwan,201149136141Garcia, M.A., J.J. Aramayona, M.A. Bregante, L.J. Fraile and C. Solans,1997693377382BP.,20102010Ruschitzka, F.T., R.H. Wenger, T. Stallmach, T. Quaschning and C. de Wit,2000971160911613Murugaiyah, V. and K.L. Chan,2007Phyllanthus niruri L. in plasma using a simple HPLC method with fluorescence detection and its application in a pharmacokinetic study.]]>852138144Karatas, A., N. Yuksel and T. Baykara,200560777782Benet, L.Z.,20131023442Nguyen, D.H., N. Sinchaipanid and A. Mitrevej,2013In vitro intestinal transport of phyllanthin across Caco-2 cell monolayers.]]>23207214Ferry, D.R., H. Traunecker and D.J. Kerr,19963210701081Wang, R.B., C.L. Kuo, L.L. Lien and E.J. Lien,200328203228Ecker, G., M. Huber, D. Schmid and P. Chiba,199956791796Polli, J.W., S.A. Wring, J.E. Humphreys, L. Huang, J.B. Morgan, L.O. Webster and C.S. Serabjit-Singh,2001in vitro P-glycoprotein assays in drug discovery.]]>299620628Fernandez, S., J.D. Rodier, N. Ritter, B. Mahler, F. Demarne, F. Carriere and V. Jannin,2008® 44/14 by digestive lipases.]]>1781367375FDA.,19971997Khan, N. and D.Q.M. Craig,200393355368Hauss, D.J., S.E. Fogal, J.V. Ficorilli, C.A. Price, T. Roy, A.A. Jayaraj and J.J. Keirns,19984 inhibitor.]]>87164169Sheen, P.C., V.K. Khetarpal, C.M. Cariola and C.E. Rowlings,1995118221227Tran, T.T.D., P.H.L. Tran and B.J. Lee,2009728390Sachs-Barrable, K., A. Thamboo, S.D. Lee and K.M. Wasan,200710319331Itoh, K., Y. Tozuka, T. Oguchi and K. Yamamoto,2002238153160