alexa Improvement of dissolution and oral absorption of ER-34122, a poorly water-soluble dual 5-lipoxygenase cyclooxygenase inhibitor with anti-inflammatory activity by preparing solid dispersion.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Proteomics & Bioinformatics

Author(s): Kushida I, Ichikawa M, Asakawa N

Abstract Share this page

Abstract Several formulation approaches were attempted to improve the dissolution and the oral absorption of ER-34122, which is a novel dual 5-lipoxygenase/cyclooxygenase inhibitor with potent anti-inflammatory activity. The solid dispersion of ER-34122 with hydroxypropylmethylcellulose (TC-5RW), which is an inert solid carrier, resulted in a significant improvement in the dissolution rate of ER-34122. The solid dispersion was prepared by a solvent evaporation method using ethanol and water. The solid-state characteristics of the solid dispersion, the corresponding physical mixture, and ER-34122 alone were investigated by X-ray powder diffraction, Fourier transform infrared spectroscopy (FTIR), and an automated controlled-atmosphere microbalance. The X-ray powder diffraction patterns suggest that the solid dispersion exists in a totally amorphous state and the others exist in a crystalline state. The FTIR spectra results suggest that ER-34122 can interact with TC-5RW through intermolecular hydrogen bonding in the solid dispersion. This interaction may cause a stabilization of ER-34122 in the higher-energy, faster-dissolving amorphous state. The dissolution rate of ER-34122 from the solid dispersion was significantly greater than that from the physical mixture or the pure drug. Furthermore, when orally administrated to beagle dogs, ER-34122 showed about a 100-fold increase in both maximum concentration (C(max)) and area under the curve of concentration versus time (AUC) compared with the pure drug. Consequently, it was determined that the solid dispersion technique with TC-5RW provides a promising way to increase the dissolution rate and the oral absorption of poorly water-soluble drugs such as ER-34122. Copyright 2002 Wiley-Liss, Inc.
This article was published in J Pharm Sci and referenced in Journal of Proteomics & Bioinformatics

Relevant Expert PPTs

Relevant Speaker PPTs

  • Bozena Futoma-Koloch
    C3 component deposition on Salmonella O48 cells characterized by sialylated lipopolysaccharide and different pattern of outer membrane proteins
    PPT Version | PDF Version
  • Sumru Savas
    No relationship between lipoprotein-associated phospholipase A2, proinflammatory cytokines, and neopterin   in Alzheimer's disease
    PPT Version | PDF Version
  • Dwi Astuti
    Phylogenetic position of Psittacula parakeet bird from Enggano Island, Indonesia based on analyses of cytochrome b gene sequences
    PPT Version | PDF Version
  • Mapitsi S Thantsha
    In vitro antagonistic effects of Listeria adhesion protein (LAP)-expressing Lactobacillus casei against Listeria monocytogenes and Salmonella Typhimurium Copenhagen
    PPT Version | PDF Version
  • Tibor Tot
    Multiparameter characterization of breast carcinoma: subgross, microscopy, proteins, and genes
    PPT Version | PDF Version
  • Monray Edward Williams
    Molecular validation of putative antimicrobial peptides for improved Human Immunodeficiency Virus diagnostics via HIV protein p24
    PPT Version | PDF Version
  • Francis Jeshira Reynoso
    The clinical phenotype of PIGN deficiency and consequences of defective GPI biogenesis
    PPT Version | PDF Version
  • Kuna Yellamma
    Kuna-Yellamma-Sri-Venkateswara-University-India-Evaluation-of-neuroprotective-effect-of-silk-protein
    PPT Version | PDF Version
  • Yosef Yarden
    Classically, the 3’untranslated region (3’UTR) is that region in eukaryotic protein-coding genes from the translation termination codon to the polyA signal. It is transcribed as an integral part of the mRNA encoded by the gene. However, there exists another kind of RNA, which consists of the 3’UTR alone, without all other elements in mRNA such as 5’UTR and coding region. The importance of independent 3’UTR RNA (referred as I3’UTR) was prompted by results of artificially introducing such RNA species into malignant mammalian cells. Since 1991, we found that the middle part of the 3’UTR of the human nuclear factor for interleukin-6 (NF-IL6) or C/EBP gene exerted tumor suppression effect in vivo. Our subsequent studies showed that transfection of C/EBP 3’UTR led to down-regulation of several genes favorable for malignancy and to up-regulation of some genes favorable for phenotypic reversion. Also, it was shown that the sequences near the termini of the C/EBP 3’UTR were important for its tumor suppression activity. Then, the C/EBP 3’UTR was found to directly inhibit the phosphorylation activity of protein kinase CPKC in SMMC-7721, a hepatocarcinoma cell line. Recently, an AU-rich region in the C/EBP 3’UTR was found also to be responsible for its tumor suppression. Recently we have also found evidence that the independent C/EBP 3’UTR RNA is actually exists in human tissues, such as fetal liver and heart, pregnant uterus, senescent fibroblasts etc. Through 1990’s to 2000’s, world scientists found several 3’UTR RNAs that functioned as artificial independent RNAs in cancer cells and resulted in tumor suppression. Interestingly, majority of genes for these RNAs have promoter-like structures in their 3’UTR regions, although the existence of their transcribed products as independent 3’UTR RNAs is still to be confirmed. Our studies indicate that the independent 3’UTR RNA is a novel non-coding RNA species whose function should be the regulation not of the expression of their original mRNA, but of some essential life activities of the cell as a whole.
    PPT Version | PDF Version
  • Shigeomi Horito
    Reconstruction of a transmembrane protein tetraspanin (CD9) into lipid bilayer by interaction of ganglioside GM3 and tetraspanin
    PPT Version | PDF Version
  • Maria A. Miteva
    In silico screening to discover inhibitors of protein-protein interactions targeting angiogenesis
    PPT Version | PDF Version
  • Konrad Sandhoff
    Lysosomal & extracellular degradation of GlcCer: Protein & lipid modifiers
    PPT Version | PDF Version
  • David Ben-Menahem
    O-glycosylation and protein evolution: the case of the LHb to CGb development
    PPT Version | PDF Version
  • Vladimir Sulimov
    “Vladimir Sulimov-Dimonta-Ltd-and-Lomonosov-Moscow-State-University-Russia-Protein-ligand-low-energy-minima-pose-analysis-Docking-target-functions-evaluation-with-the-FLM-program”
    PPT Version | PDF Version
  • Xingmin Sun
    A chimeric protein (mTcd138) comprising the glucosyltransferase and domains of toxin B and the receptor binding domain of toxin A provides full protection against Clostridium difficile infection in mice
    PPT Version | PDF Version

Recommended Conferences

  • 9th International Conference on Bioinformatics
    October 23-24, 2017 Paris, France
  • 9th International Conference and Expo on Proteomics
    October 23-25, 2017 Paris, France

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords