Dissolution rate development

The formation of deposits on platinised anodes can cause anode degradationThus dissolved impurities present in water which are liable to oxidation to insoluble oxides, namely Mn, Fe, Pb and Sn, can have a detrimental effect on anode life. In the case of MnOj films it has been stated that MnOj may alter the relative proportions of Cl, and O, produced and thus increase the Pt dissolution rate Fe salts may be incorporated into the TiO, oxide film and decrease the breakdown potential or form thick sludgy deposits. The latter may limit electrolyte access and iead to the development of localised acidity, at concentrations sufficient to attack the underlying substrate . 

Sintered and sprayed ceramic anodes have been developed for cathodic protection applications. The ceramic anodes are composed of a group of materials classified as ferrites with iron oxide as the principal component. The electrochemical properties of divalent metal oxide ferrites in the composition range 0- lA/O-0-9Fe2O3 where M represents a divalent metal, e.g. Mg, Zn, Mn, Co or Ni, have been examined by Wakabayashi and Akoi" . They found that nickel ferrite exhibited the lowest consumption rate in 3% NaCl (of 1 56 g A y at 500 Am and that an increase in the NiO content to 40mol 7o, i.e. O NiO-O-bFejO, reduced the dissolution rate to 0-4gA y at the expense of an increase in the material resistivity from 0-02 to 0-3 ohm cm. 

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. 

G. Levy, J. R. Leonards, and J. A. Procknal, Development of in vitro dissolution tests which correlate quantitatively with dissolution rate-limited drug absorption in man, J. Pharm. Sci., 54, 1719-1722 (1966). K. A. Javaid and D. E. Cadwallader, Dissolution of aspirin from tablets containing various buffering agents, J. Pharm. Sci., 61, 1370-1373 (1972). 

In a typical research and development setting, in the event that a new drug candidate is recognized by the drug-discovery group, then the dissolution rate constant K for that compound under specified hydro-dynamic conditions can be determined from powder dissolution data and practical size analysis by microscopy. 

The intrinsic dissolution rate is the rate of mass transfer from the solid phase to the liquid phase. Information on the intrinsic dissolution rate is important in early drug product development. It has been suggested that drugs with intrinsic dissolution rates of less than 0.1 mg/(min cm2) will have dissolution rate-limited absorption, while drugs with intrinsic dissolution rates greater than 0.1 mg/ (min cm2) are unlikely to have dissolution rate problems. 

Figure 7 Rotating disk to evaluate the intrinsic dissolution rate of compounds. The amount of drug dissolving per unit area is the same everywhere on the disk surface. This simplification makes the disk a powerful experimental tool in drug discovery and development. 

Although, the pH-partition hypothesis has not been found to be universally applicable, it has resulted in the recognition of the important contribution of GI pH to permeability and to the dissolution rate of solid dosage forms. This theory does not consider the solubility of the drug, which is a critical physicochemical parameter in the oral absorption process. Dressman et al. [34] developed an absorption potential concept that takes the two parameters into account. The absorption potential is defined as... 

The surface area of a solid material is important in that it provides information on the available void spaces on the surfaces of a powdered solid [48]. In addition, the dissolution rate of a solid is partially determined by its surface area. The most reproducible measurements of the surface area of a solid are obtained by adsorbing a monolayer of inert gas onto the solid surface at reduced temperature and subsequently desorbing this gas at room temperature. The sorption isotherms obtained in this technique are interpreted using the equations developed by Brunauer, Emmett, and Teller, and therefore the technique is referred to as the B.E.T. method [49]. The surface area is obtained in units of square meters of surface per gram of material. 

Evaluation of the dissolution rates of solid drugs is extremely important in the development, formulation, and quality control of solid pharmaceuticals. The... 

Since the rate of absorption of many drugs from the gastrointestinal tract is controlled by their dissolution rate, this becomes the rate-limiting step. Accurate and reliable measurements of dissolution rate are therefore required in the pharmaceutical sciences. The measurement and interpretation of the dissolution rates of solid drugs in the pure state or from formulations, such as tablets, capsules, and suppositories, has an extensive pharmaceutical literature [95-100]. Moreover, the design, operation, and interpretation of dissolution rate measurements on pharmaceutical solids have been the subject of considerable scientific study, technical development, and debate. 

Figure 8 shows the effect of the alkaline concentration in TMAH solutions on the contrast and sensitivity of the new resist. Sensitivity of the resist increases as the alkaline concentration increases, however, the contrast is maxima (4.72) at 0.83% TMAH solution. This means that the higher concentration over 0.83% cannot distinguish the difference of the dissolution rate between the unexposed and exposed resist film. For instance, the higher concentrated developer also attacks the exposed areas and the loss of resist thickness occurs. The alkaline concentration in TMAH solution, therefore, is optimized at 0.83%. This developer concentration was subjected to the following lithographic evaluation. 

Various devices can be used to determine the kinetics and rates of chemical weathering. In addition to the batch pH-stats, flow through columns, fluidized bed reactors and recirculating columns have been used (Schnoor, 1990). Fig. 5.15a illustrates the fluidized bed reactor pioneered by Chou and Wollast (1984) and further developed by Mast and Drever (1987). The principle is to achieve a steady state solute concentration in the reactor (unlike the batch pH-stat, where solute concentrations gradually build up). Recycle is necessary to achieve the flow rate to suspend the bed and to allow solute concentrations to build to a steady state. With the fluidized bed apparatus, Chou and Wollast (1984) could control the AI(III) concentration (which can inhibit the dissolution rate) to a low level at steady state by withdrawing sample at a high rate. 

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