Multiphase release

United States Patent 4,767,628 assigned to Imperial Chemical Industries describes a similar lactide/glycolide delivery system for LHRH polypeptide (122,123). A multiphase release pattern is again postulated. The first phase occurs by diffusion of drug through aqueous polypeptide domains linked to the exterior surface of the matrix. 

Initially, the drug concentration profile is specified by a computer model, which is then built in the deposition process. Complex drug delivery systems can be created in this way, such as the release of multiple drugs or multiphasic release of a single drug. 

Laboratory experiments by our group showed that reaction 13 occurs very slowly in the gas phase (10). However, in the presence of ice surfaces the reaction proceeds very efficiently the product CI2 is immediately released to the gas phase, whereas HNO3 remains frozen in the ice (11). Other groups also found that this heterogeneous (i.e., multiphase) process occurs efficiently (12,13), and that a similar reaction also occurs with N2O5 as a reactant ... 

Steele et al. 1987 Battaglia et al. 1988). In summary, previous pharmacologic studies indicate that MDMA and related psychotropic amphetamines have a multiphasic effect marked by an acute release of 5-HT, which may be reversible, followed by a ehronic decrease in 5-HT markers probably due to axon degeneration. 

Similar to gasoline, the properties of DNAPLs such as immiscibility with water, volatility, and solubility of some of its components cause the presence of multiphase (pure product, solute, gas, and adsorbate) products and movement that is typical of the phenomena associated with DNAPL release. The theory associated with the interaction of gasoline with soil is applicable to DNAPLs. However,... 

Abriola LM, Pinder GF (1985) A multiphase approach to the modeUing of porous media contamination by organic compounds. Water Resour Res 21 11-18 Ahuja LR (1982) Release of soluble chemicals from soil to runoff. Trans Am Soc Agri Eng 25 948-953... 

Current and future combustor applications require increased energy release with reduced chamber volume, increased equilibrium temperature, multiphase reacting flows with radiative heat transfer, and sometimes even with electric and magnetic fields. A thorough understanding of the basic physical and chemical... 

The geometry of the ramjet system simulated is shown in Fig. 7.1, which consists of a cylindrical inlet connected to a central dump combustor that has an exhaust nozzle. This specific geometry was chosen because extensive studies have been made in the past of the interaction between acoustics, vorticity dynamics, and chemical energy release in this system [17-20]. These earlier gas-phase flow studies are very helpful in interpreting the current multiphase flow simulations. 

The present investigation applies deterministic methods of continuous mechanics of multiphase flows to determine the mean values of parameters of the gaseous phase. It also applies stochastic methods to describe the evolution of polydispersed particles and fluctuations of parameters [4]. Thus the influence of chaotic pulsations on the rate of energy release and mean values of flow parameters can be estimated. The transport of kinetic energy of turbulent pulsations obeys the deterministic laws. 

Further in vivo studies revealed that the arteriolar constriction that follows mast cell activation via inosine, is the result of histamine and thromboxane release and that A3AR is involved in mediating this response (Shepherd and Duling 1996 Shepherd et al. 1996 Fozard et al. 1996 Reeves et al. 1997). Inosine, which does not bind to Aj or A2 receptors, thus elicits a monophasic arteriolar constrictor response distinct from the multiphasic dilator/constrictor response to adenosine (Jin et al. 1997). 

Both intracellular release and transmembrane flux contribute to the rise in intracellular Ca2+.14,15 The rise in keratinocyte intracellular Ca2+ in response to raised extracellular Ca2+ has two phases (a) an initial peak, not dependent on extracellular Ca2+ and (b) a later phase that requires extracellular Ca2+.14 An early response of human keratinocytes to increases in extracellular Ca2+ is an acute increase in intracellular Ca2+. Stepwise addition of extracellular Ca2+ to neonatal human keratinocytes is followed by a progressive increase in intracellular Ca2+, where the initial spike of increased intracellular Ca2+ is followed by a prolonged plateau of higher intracellular Ca2+.16 The response of intracellular Ca2+ to increased extracellular Ca2+ in keratinocytes is saturated at 2.0 mM extracellular Ca2+.16,17 The response of intracellular Ca2+ to increased extracellular Ca2+ in keratinocytes resembles the response in parathyroid cells, in that a rapid and transient increase in intracellular Ca2+ is followed by a sustained increase in intracellular Ca2+ above basal level. This multiphasic response is attributed to an initial release of Ca2+ from intracellular stores followed by an increased influx of Ca2+ through voltage-independent cation channels. The keratinocyte and parathyroid cell contains a similar cell membrane calcium receptor thought to mediate this response to extracellular Ca2+. This receptor can activate the phospholipase-C pathway, leading to an increase... 

Robert Langer, Polymer Systems for Controlled Release of Macromolecules, Immobilized Enzyme Medical Bioreactors, and Tissue Engineering J. J. Linderman, P. A. Mahama, K. E. Forsten, and D. A. Lauffenburger, Diffusion and Probability in Receptor Binding and Signaling Rakesh K. Jain, Transport Phenomena in Tumors R. Krishna, A Systems Approach to Multiphase Reactor Selection... 

The issues to be solved for direct fluorinations are heat release and mass transfer via the gas-liquid interface. Multiphase microstructured reactors enable process intensification [230,248-250,304—306]. Often geometrically well-defined interfaces are formed with large specific values, for example, up to 20 000 m2/m3 and even more. These areas can be easily accessible, as flow conditions are often highly periodic and transparent microreactors are available. For the nondispersing... 

This guideline covers only nonroutine or accidental events. Many hazardous events start with the discharge or loss of containment of a flammable and/or toxic material from a vessel or pipe. These discharges, which may take the form of vapor, liquid, solid, or multiphase vapor-liquid-solid mixtures, may be released into a confined area, such as a dike, building, or an equipment array, or into an open, unconfined area. The sources of these releases could be holes in vessels or pipelines, open pressure-relief devices, pipe ruptures, flange and seal leaks, or catastrophic vessel mptures. The range of releases is illustrated in Figure 2.1. 

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