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Reports from A.O. Nornoo and colleagues advance knowledge in pharmacokinetics
2009 MAY 12 - (NewsRx.com) -- According to a study from the United States, "The overall goal of this study was to develop cremophor-free oral microemulsions of paclitaxel (PAC) to enhance its permeability and oral absorption. The mechanism of this enhancement, as well as characteristics of the microemulsions relevant to the increase in permeability and absorption of the low solubility, low permeability PAC was investigated." "Phase diagrams were used to determine the macroscopic phase behavior of the microemulsions and to compare the efficiency of different surfactant-oil mixtures to incorporate water. The microemulsion region on the phase diagrams utilizing surfactant-myvacet oil combinations was in decreasing order: lecithin: butanol: myvacet oil (LBM. 48.5%) > centromix CPS: 1-butanol: myvacet oil (CPS, 45.15%) > capmcl MCM: polysorbate 80: myvacet oil (CPM, 27.6%) > capryol 90: polysorbate 80: myvacet oil (CP-P80, 23.9%) > capmul: myvacet oil (CM, 20%). Oil-in-water (o/w) microemulsions had larger droplet sizes (687-1010 nm) than the water-in-oil (w/o) microemulsions (272-363 nm) when measured using a Zetasizer nano series particle size analyzer. Utilizing nuclear magnetic resonance spectroscopy (NMR), the self-diffusion coefficient (D) of PAC in CM, LBM and CPM containing 10% of deuterium oxide (D2O) was 2.24 x 10(-11),1.97 x 10(-11) and 0.51 x 10(-11) m(2)/s, respectively. These values indicate the faster molecular mobility of PAC in the two w/o microemulsions (CM and LBM) than the o/w microemulsion - CPM. The in situ permeability of PAC through male CD-IGS rat intestine was 3- and 11-fold higher from LBM and CM, respectively, than that from the control clinical formulation, Taxol (R) (CE, cremophor: ethanol) in a single pass perfusion study. PAC permeability was significantly increased in the presence of the pgp/CYP3A4 inhibitor cyclosporine A (CsA). This enhancement may be attributed to the pgp inhibitory effect of the surfactants, oil and/or the membrane perturbation effect of the surfactants. The oral disposition of PAC in CM, LBM and CPM compared to CE was studied in male CD-IGS rats after a single oral dose (20 mg/kg). The area-under-the-curve of PAC in CM was significantly larger than LBM, CPM and CE. Oral microemulsions of PAC were developed that increased both the permeability and AUC of PAC as compared to CE," wrote A.O. Nornoo and colleagues. The researchers concluded: "Published by Elsevier B.V." Nornoo and colleagues published their study in European Journal of Pharmaceutics and Biopharmaceutics (Oral microemulsions of paclitaxel: In situ and pharmacokinetic studies. European Journal of Pharmaceutics and Biopharmaceutics, 2009;71(2):310-317). For more information, contact A.O. Nornoo, Albany College Pharmacy, Dept. of Pharmaceutical Science, 106 New Scotland Avenue, Albany, NY 12208, USA. Publisher contact information for the European Journal of Pharmaceutics and Biopharmaceutics is: Elsevier Science BV, PO Box 211, 1000 AE Amsterdam, Netherlands. Keywords: United States, Albany, Behavior, Biopharmaceuticals, Biopharmaceutics, Drugs, Magnetic Resonance, Paclitaxel, Pharmaceuticals, Pharmacokinetics, Spectroscopy, Surgery, Therapies, Therapy, Treatment. This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2009, Life Science Weekly via NewsRx.com.
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