Design and preparation of controlled floating gastroretentive delivery systems for enhanced fexofenadine hydrochloride oral bioavailability

Purpose: To design and prepare effervescent floating gastroretentive tablets for controlledfexofenadine hydrochloride (HCl) release and enhanced oral bioavailability.Method: Various tablet formulations of the drug were prepared by direct compression. A systematic approach in the design of the formulations was adopted, where, first, formulations consisting of single polymers with a high polymer : sodium bicarbonate ratio were investigated for its physicochemical properties (in-vitro floating behaviour, drug release profile, etc). Next, improvement of tablets’ properties was achieved by decreasing polymer : sodium bicarbonate ratio. Subsequently, a final optimization step involved blending polymers at different polymer : polymer ratios. The formulations were evaluated in vitro and in vivo in albino rabbitsResults: The formulation consisting of hydroxypropyl methylcellulose K15M/hydroxypropylmethyl cellulose K100LV at 1 : 2 ratio (F8) showed good floating properties (14 s floating lag time) with nearly zero order controlled drug release for 24 h (R2 = 0.9876). In-vivo bioavailability studies of F8 in albino rabbits showed a significant increase in area under the curve (AUC, 134 %, p < 0.05) and hence an improvement in its oral bioavailability, compared to a commercial conventional product.Conclusion: The good quality of the effervescent floating gastroretentive tablets of fexofenadine HCl developed is an indication that the approach used is suitable for the formulation of the drug for controlled drug release and enhanced oral bioavailabiliy.Keywords: Effervescent, Floating, Gastroretentive, Fexofenadine, Bioavailabilit

Multidimensional Proteomics Analysis of Amniotic Fluid to Provide Insight into the Mechanisms of Idiopathic Preterm Birth

Though recent advancement in proteomics has provided a novel perspective on several distinct pathogenetic mechanisms leading to preterm birth (inflammation, bleeding), the etiology of most preterm births still remains elusive. We conducted a multidimensional proteomic analysis of the amniotic fluid to identify pathways related to preterm birth in the absence of inflammation or bleeding.A proteomic fingerprint was generated from fresh amniotic fluid using surface-enhanced laser desorbtion ionization time of flight (SELDI-TOF) mass spectrometry in a total of 286 consecutive samples retrieved from women who presented with signs or symptoms of preterm labor or preterm premature rupture of the membranes. Inflammation and/or bleeding proteomic patterns were detected in 32% (92/286) of the SELDI tracings. In the remaining tracings, a hierarchical algorithm was applied based on descriptors quantifying similarity/dissimilarity among proteomic fingerprints. This allowed identification of a novel profile (Q-profile) based on the presence of 5 SELDI peaks in the 10-12.5 kDa mass area. Women displaying the Q-profile (mean+/-SD, gestational age: 25+/-4 weeks, n = 40) were more likely to deliver preterm despite expectant management in the context of intact membranes and normal amniotic fluid clinical results. Utilizing identification-centered proteomics techniques (fluorescence two-dimensional differential gel electrophoresis, robotic tryptic digestion and mass spectrometry) coupled with Protein ANalysis THrough Evolutionary Relationships (PANTHER) ontological classifications, we determined that in amniotic fluids with Q-profile the differentially expressed proteins are primarily involved in non-inflammatory biological processes such as protein metabolism, signal transduction and transport.Proteomic profiling of amniotic fluid coupled with non-hierarchical bioinformatics algorithms identified a subgroup of patients at risk for preterm birth in the absence of intra-amniotic inflammation or bleeding, suggesting a novel pathogenetic pathway leading to preterm birth. The altered proteins may offer opportunities for therapeutical intervention and future drug development to prevent prematurity

Delineation of VEGF-regulated genes and functions in the cervix of pregnant rodents by DNA microarray analysis

<p>Abstract</p> <p>Background</p> <p>VEGF-regulated genes in the cervices of pregnant and non-pregnant rodents (rats and mice) were delineated by DNA microarray and Real Time PCR, after locally altering levels of or action of VEGF using VEGF agents, namely siRNA, VEGF receptor antagonist and mouse VEGF recombinant protein.</p> <p>Methods</p> <p>Tissues were analyzed by genome-wide DNA microarray analysis, Real-time and gel-based PCR, and SEM, to decipher VEGF function during cervical remodeling. Data were analyzed by EASE score (microarray) and ANOVA (Real Time PCR) followed by Scheffe's <it>F</it>-test for multiple comparisons.</p> <p>Results</p> <p>Of the 30,000 genes analyzed, about 4,200 genes were altered in expression by VEGF, i.e., expression of about 2,400 and 1,700 genes were down- and up-regulated, respectively. Based on EASE score, i.e., grouping of genes according to their biological process, cell component and molecular functions, a number of vascular- and non-vascular-related processes were found to be regulated by VEGF in the cervix, including immune response (including inflammatory), cell proliferation, protein kinase activity, and cell adhesion molecule activity. Of interest, mRNA levels of a select group of genes, known to or with potential to influence cervical remodeling were altered. For example, real time PCR analysis showed that levels of VCAM-1, a key molecule in leukocyte recruitment, endothelial adhesion, and subsequent trans-endothelial migration, were elevated about 10 folds by VEGF. Further, VEGF agents also altered mRNA levels of decorin, which is involved in cervical collagen fibrillogenesis, and expression of eNO, PLC and PKC mRNA, critical downstream mediators of VEGF. Of note, we show that VEGF may regulate cervical epithelial proliferation, as revealed by SEM.</p> <p>Conclusion</p> <p>These data are important in that they shed new insights in VEGF's possible roles and mechanisms in cervical events near-term, including cervical remodeling.</p

Hepcidin, Serum Iron, and Transferrin Saturation in Full-Term and Premature Infants during the First Month of Life: A State-of-the-Art Review of Existing Evidence in Humans.

Neonates regulate iron at birth and in early postnatal life. We reviewed literature from PubMed and Ovid Medline containing data on umbilical cord and venous blood concentrations of hepcidin and iron, and transferrin saturation (TSAT), in human neonates from 0 to 1 mo of age. Data from 59 studies were used to create reference ranges for hepcidin, iron, and TSAT for full-term-birth (FTB) neonates over the first month of life. In FTB neonates, venous hepcidin increases 100% over the first month of life (to reach 61.1 ng/mL; 95% CI: 20.1, 102.0 ng/mL) compared with umbilical cord blood (29.7 ng/mL; 95% CI: 21.1, 38.3 ng/mL). Cord blood has a high concentration of serum iron (28.4 μmol/L; 95% CI: 26.0, 31.1 μmol/L) and levels of TSAT (51.7%; 95% CI: 46.5%, 56.9%). After a short-lived immediate postnatal hypoferremia, iron and TSAT rebounded to approximately half the levels in the cord by the end of the first month. There were insufficient data to formulate reference ranges for preterm neonates