Kinetics of Silica Condensation In Brines

Homogeneous nucleation and growth of silica from brines supersaturated in silicic acid has been studied over a range of pH (4.5-6.7), temperature (75-105 C), salinity, and silicic acid concentration (700 to 1200 ppm as SiO{sub 2}). The experimental technique involved analyses for molybdate-reactive silicic acid as a function of time after a supersaturated solution of H{sub 4}SiO{sub 4} was prepared by mixing aliquots of a stock silicate solution with buffered brine. The isothermal rate of SiO{sub 2} condensation is a strong function of supersaturation (C/C{sub eq}), pH, and salinity. The overall kinetics follow what is expected from the general theory of phase transitions and are adequately described by the Volmer-Becker-Doring expressions for condensation from solution. At supersaturations less than about 3, an induction or transition time is observed. It amounts to several hundred minutes at supersaturations of about 2.

Transdermal Pharmacology of Small Molecule Cyclic C5a Antagonists

Overproduction or underregulation of the proinflammatory complement component C5a has been implicated in numerous immune and inflammatory conditions. Therefore, targeting the C5a receptor (C5aR) has become an innovative strategy for antiinflammatory drug development. The novel cyclic peptide C5aR antagonist, AcF-[OP(D-Cha)WR] (PMX53), attenuates injury in numerous animal models of inflammation following intravenous, subcutaneous, intraperitoneal, and oral administration. In the present study the transdermal pharmacology of PMX53 and three analogs designed with increased lipophilicity, hydrocinnamate-[OP(D-Cha)WCit] (PMX200), AcF-[OP(D-Cha)WCit] (PMX201) and hydrocinnamate-[OP(D-Cha)WR] (PMX205), have been examined in order to assess their transdermal permeability and inhibitory effect on C5a-mediated lipopolysaccharide (LPS)-induced systemic responses. In the rat, PMX53, PMX201, and PMX205, were bioavailable following topical dermal administration (10 mg/50 cm(2) site/rat). All analogs functionally antagonized neutropenia and hypotension induced by systemic challenge with LPS (I mg/kg i.v.). Interestingly, PMX200 attenuated LPS-induced neutropenia more effectively than other analogs, despite undetectable (< 5 ng/ml) circulating levels following topical administration. In conclusion, we have demonstrated that cyclic peptide C5aR antagonists can penetrate transdermally sufficiently to have systemic effects. However, increasing lipophilicity in these compounds did not result in increased blood levels. Nonetheless, topical application of C5aR antagonists produced circulating levels of the drugs that antagonized the LPS-induced systemic responses of neutropenia and hypotension. This suggests that these small-molecule C5aR antagonists may be developed for topical administration for the treatment of local and systemic inflammatory conditions in the human and veterinary pharmaceutical markets