Dissolution surface area

In this chapter we will provide a brief overview of the early approaches to bioavailability enhancement by use of simple lipid-based delivery systems (lipid solutions, emulsions etc), and then describe recent progress in the application of self-emulsifying- and microemulsion-based formulations. The effects of lipids on the oral bioavailability of co-administered poorly water-soluble drugs may also be classified from a mechanistic (and to a degree, historical) perspective as physicochemically mediated effects (solubility, dissolution, surface area) and biochemically mediated effects (metabolism, transport related events), and these will be approached separately. It is readily apparent, however, that in many cases physicochemically and biochemically mediated mechanisms will operate side by side. In some instances, bioavailability may also be enhanced by the stimulation of intestinal lymphatic transport, and these studies will be addressed in a separate section. 

If the spreading is into a limited surface area, as in a laboratory experiment, the film front rather quickly reaches the boundaries of the trough. The film pressure at this stage is low, and the now essentially uniform film more slowly increases in v to the final equilibrium value. The rate of this second-stage process is mainly determined by the rate of release of material from the source, for example a crystal, and the surface concentration F [46]. Franses and co-workers [47] found that the rate of dissolution of hexadecanol particles sprinkled at the water surface controlled the increase in surface pressure here the slight solubility of hexadecanol in the bulk plays a role. 

Other Measurements. Other tests include free moisture content, rate of dissolution and undissolved residue in acids and alkaH, resin and plasticizer absorption, suspension viscosity, and specific surface area. Test procedures for these properties are developed to satisfy appHcation-related specifications. 

Polycondensation reactions (eqs. 3 and 4), continue to occur within the gel network as long as neighboring silanols are close enough to react. This increases the connectivity of the network and its fractal dimension. Syneresis is the spontaneous shrinkage of the gel and resulting expulsion of Hquid from the pores. Coarsening is the irreversible decrease in surface area through dissolution and reprecipitation processes. 

Soaking a siUca gel in dilute ammonium hydroxide solution at 50—85°C can result in significant coarsening of the gel texture (5). Aging and thermal treatments result in a one-way process, ie, loss of specific surface area and in increase in pore size. The pore size can also be enlarged by dissolution of some of the siUca. Treating a siUca gel with O.S-N KOH or dilute HF can enlarge the pores from 0.7 to 3.7 nm (3). 

Both titanium and boron can be added as grain refiners to ensure small grain size and hence high surface area grain boundaries. This reduces the risk of preferential attack at grain boundaries and promotes more uniform dissolution. 

It was found that the dissolution rate of the material depends both on its surface area and on its crystalline size, but the importance of the crystalline size seems to be greater. The empiric equation describing the above dependence of the leaching rate on these two parameters is as follows (130) ... 

It is important to distinguish clearly between the surface area of a decomposing solid [i.e. aggregate external boundaries of both reactant and product(s)] measured by adsorption methods and the effective area of the active reaction interface which, in most systems, is an internal structure. The area of the contact zone is of fundamental significance in kinetic studies since its determination would allow the Arrhenius pre-exponential term to be expressed in dimensions of area"1 (as in catalysis). This parameter is, however, inaccessible to direct measurement. Estimates from microscopy cannot identify all those regions which participate in reaction or ascertain the effective roughness factor of observed interfaces. Preferential dissolution of either reactant or product in a suitable solvent prior to area measurement may result in sintering [286]. The problems of identify-... 

The following brief account is concerned with factors that affect the acces-sibihty of the OH groups of cellulose, since this is the determining factor for its dissolution, hence subsequent derivatization. Electron microscopy. X-ray scattering and porosimetry of cellulose fibers have clearly shown the presence of non-uniform pores, capillaries, voids and interstices in the fiber surface [25]. Consequently, the total surface area of cellulose fibers exceeds by far the geometrical outer surface. Pore structure determines the internal... 

Electrochemical machining is performed in concentrated solntions of salts alkali chlorides, snlfates, or nitrates. Very high current densities are nsed hundreds or thousands of kA/m when referring to the surface area of the anodic working sections. At a current density of 10" mA/cm, the rate of iron dissolution is about 0.15 mm/min. This should also be the rate of advance of the cathode in the direction of the anode. High rates of solution flow through the working gap are used to eliminate the reaction products and heat evolved (e.g., flow rates of 10" cm/s). 

The surface of the base metal is anodically polarized under the effect of local cells. For a graphical analysis of the phenomena, one must construct the polarization curves for the partial currents at the base metal as well as the overall anodic 4 vs. E curve reflecting the effective rate of dissolution of this metal under anodic polarization. The rate of the cathodic process, 4, at the inclusions is described by the corresponding cathodic polarization curve (since the surface areas of anodic and cathodic segments differ substantially, currents rather than current densities must be employed here). At open circuit the two rates are identical. 

Investigation of the differences in crystal packing between (431) and (426) from comparison of their respective X-ray structures, revealed that (431) was more tightly packed than (442), reflected in their respective melting points of 235 and 170 °C. It was postulated that the absence of in vivo activity for (431) may be explained by the resultant reduction in water solubility and dissolution rate compared with (426). The comparatively high calculated polar surface area of (431) (122.5A ) compared with (426) (89.3 A ) was also proposed as a factor influencing the marked difference in bioavailability between the two related compounds. Compound (426) (SLV-319) is currently being developed with Bristol-Myers Squibb for the potential treatment of obesity and other metabolic disorders. Phase I trials for obesity were started in April 2004. Earlier Phase I clinical trials for the treatment of schizophrenia and psychosis, which commenced in April 2002, appear to have been abandoned. 

Consider a situation where a fluid flows past a solid surface from which a component A is being transferred. Such a situation can be encountered in simple processes like drying or dissolution. The bulk of the fluid can be considered to be in turbulent flow, while there is a laminar film adjacent to the solid surface. The major change in the concentration of component A occurs across this laminar film. It is found that the rate of transfer of A (denoted by dNA/di) is proportional to the surface area, S, and to the difference in the concentration of A in the fluid adjacent to the solid surface and that in the bulk of the fluid. Denoting these concentrations as CAs and CAb respectively (Figure 3.23), one can write... 

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