Dissolution Improvement of Poorly Water Soluble Drug Valsartan and Improving Flow Properties of Solid Dispersion

The aim of the present investigation is to improve the dissolution of poorly water soluble drug valsartan by preparing solid dispersions and also to evaluate the effect of different inert carriers on flow properties of solid dispersion. Valsartan is a poorly soluble drug useful in the treatment of hypertension. Absorption window of valsartan is stomach and upper part of small intestine. One possible way to improve dissolution rate is solid dispersions of the drug. The solid dispersions were prepared by solvent evaporation method using HPMC E5 LV as water soluble carrier, as use of HPMC low viscosity polymers for solid dispersion preparations were reported in literature. But film formation took place during solid dispersion formulation and was creating difficulty in releasing the drug from formulation; and those solid dispersions, were not free flowing. Thus such preparations are not useful from the formulation development point of view. So to improve the flow properties some inert material were tried like microcrystalline cellulose (MCC) and lactose. The solid dispersions were evaluated for drug content, solubility and dissolution studies. In vitro drug release of solid dispersions was studied by USP type II paddle dissolution apparatus. For the solid dispersion the solubility and dissolution of the drug increased with the increase in the carrier concentration. Probable mechanisms of improved solubility and dissolution were characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (Powder XRD) and Scanning Electron Microscopy (SEM) of drug, physical mixture and solid dispersions. This study revealed that solid dispersions technique is promising and useful for valsartan to improve its solubility and dissolution and incorporation of inert carriers improved the flow property of solid dispersion.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Activation of Akt by the Bacterial Inositol Phosphatase, SopB, is Wortmannin Insensitive

Salmonella enterica uses effector proteins translocated by a Type III Secretion System to invade epithelial cells. One of the invasion-associated effectors, SopB, is an inositol phosphatase that mediates sustained activation of the pro-survival kinase Akt in infected cells. Canonical activation of Akt involves membrane translocation and phosphorylation and is dependent on phosphatidyl inositide 3 kinase (PI3K). Here we have investigated these two distinct processes in Salmonella infected HeLa cells. Firstly, we found that SopB-dependent membrane translocation and phosphorylation of Akt are insensitive to the PI3K inhibitor wortmannin. Similarly, depletion of the PI3K regulatory subunits p85α and p85ß by RNAi had no inhibitory effect on SopB-dependent Akt phosphorylation. Nevertheless, SopB-dependent phosphorylation does depend on the Akt kinases, PDK1 and rictor-mTOR. Membrane translocation assays revealed a dependence on SopB for Akt recruitment to Salmonella ruffles and suggest that this is mediated by phosphoinositide (3,4) P2 rather than phosphoinositide (3,4,5) P3. Altogether these data demonstrate that Salmonella activates Akt via a wortmannin insensitive mechanism that is likely a class I PI3K-independent process that incorporates some essential elements of the canonical pathway