Dissolution rate data

Many of the same factors which complicate the interpretation of laboratory kinetic studies are among the most important limitations on the application of laboratory dissolution rate data to natural systems. These include uncertainty about 1) the effective surface area in natural systems (56,57) 2) the extent to which surface area and surface roughness change with reaction progress ( 18) and 3) the magnitude of solution composition effects on rates in natural systems. 

Fig. 5. Plot showing the effect of radiation field intensity on U02 dissolution rate (data extracted from Christensen Sunder 1996). Dissolution rates were obtained by electrochemical measurements. A significant enhancement in the reaction rate is observed with dose and in the presence of oxygen.

Table I contains dissolution rate data for an m-cresol novolac, 1, and for the novolac containing 15 wt% of the dicizoquinone 2. Using...

Tablet disintegration was once considered a sufficient criterion to predict in vivo absorption. This was proven inadequate, however, and dissolution is now recognized as a better criterion. Regulatory agencies now require dissolution rate data for all new oral formulations. The increasingly wide acceptance of dissolution as the best available in vitro parameter to predict in vivo absorption is reflected in the proliferation of such tests in official compendia.

The delay in the peak aluminium concentration relative to calcium and magnesium makes sense when comparing the dissolution rates of carbonate and aluminosilicate minerals. Comparing dissolution rate data on calcite (Morse, 1983) with those on albite (Chou Wollast, 1985 Knauss Wolery, 1986) shows that at a pH of 3 calcite dissolves considerably faster, with a difference of several orders of magnitude. 

The study of the dissolution behavior involves measurements of film thickness as a function of time. Although the simplest procedure requires manual measurements of the initial thickness and the thickness after development for a given period of time to generate average dissolution rates, automated in situ thickness measurement methods are much more preferred as kinetics information is much more valuable than simple average dissolution rate data. Two methodologies are available laser interferometry and quartz crystal microbalance (QCM). 

Figure 12.6 Comparison of the accuracy of the Dill model, Mack model, and enhanced (advanced) Mack model in modeling the dissolution rate data of AZ 7908 resist developed in 300-MIF developer. (Courtesy of R. Dammel.)...

In addition to the above, polymer dissolution rate data have been used to determine glass transition temperature and other thermodynamic parameters associated with polymorphic changes [21]. Dissolution has also found a variety of uses in the pharmaceutical sciences. In the development of microcapsules for sustained release dosage forms [22], the mechanism of drug transport is governed by the dissolution of the polymer. Cooney [23] studied the dissolution of pharmaceutical tablets in the design of sustained release forms. Ozturk et al. [24, 25] showed that the dissolution of the polyacid, which is used in enteric-coated tablets, was the controlling step in the release kinetics mechanism. 

Dissolution rate data, for example, are conveniently expressed in this way. The mass transfer coefficient, in the Sherwood number, depends on the solution velocity, u, raised to the power a. It is possible, therefore, that the effect of solution velocity on crystal growth may also be represented by an equation of this type in the region where diffusion influences the growth rate. 

Dissolution rate data obtained under forced convection conditions can be correlated by means of equation 6.64 or 6.65. As described in section 6.2.2, equation 6.64 is the preferred relationship on theoretical grounds, since Sh = 2 for mass transfer by convection in stagnant solution (Re = 0), whereas equation 6.65 incorrectly predicts a zero mass transfer rate (Sh = 0) for this condition. However, at reasonably high values of Sh (>100) the use of the simpler equation 6.65 is quite justified. The exponent of the Schmidt number b is usually taken to be and for mass transfer from spheres the exponent of the Reynolds number a =... 

Dissolution rate data for potash alum are plotted in accordance with equations 6.108 and 6.110 with e = 0.95, in Figure 633, where it can be seen that the results lie reasonably close ( 20%) to the predicted values. However, it should be noted that equation 6.110 is very sensitive to values of e as e —> 1, so it cannot be applied with any reliabihty to very lean beds of dissolving particles and certainly not to the dissolution of single particles. 

There are in addition several other factors that accelerate corrosion and must betaken into account these include crevices, galvanic coupling, tensile stress, aeration, presence of impurities, surface finish, etc. If these were also taken into consideration then several million experiments would have to be performed to compile such data. There are many instances where two or more chemicals exert a marked synergistic action such that low dissolution rates obtained in either environment become much greater in the presence of both. Further, the corrosiveness of a chemical will be affected by the presence of certain impurities, which may act as either accelerators or inhibitors. To take all these factors into account would add to an already impossible task and as Evans has remarked, There are not enough trained investigators in the world to obtain the empirical information to cover all combinations of conditions likely to arise . Unfortunately corrosion science has not yet reached the stage where prediction, based on a few well established laws, allows selection of materials to be made without recourse to a vast amount of data. 

Figure 4.52. Coefficients of variation that reflect both tablet to tablet and analytical variability. For formulation B, particularly strengths 2 and 3, the drop in CV with higher cumulative release (a - b) is marked, cf. Fig, 4.50. When the dissolution rate is high, individual differences dominate, while towards the end analytical uncertainty is all that remains. The very low CVs obtained with strength 3 of formulation A ( 0.7-0.8%, data offset by +10% for clarity) are indicative of the analytical uncertainty. Because content uniformity is harder to achieve the lower the drug-to-excipient ratio, this pattern is not unexpected.

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. 

Dissolution test data will be required in all cases (and for all strengths of product) for development and routine control and should be based on the most suitable discriminatory conditions. The method should discriminate between acceptable and unacceptable batches based on in vivo performance. Wherever possible Ph Eur test methods should be used (or alternatives justified). Test media and other conditions (e.g., flow through rate or rate of rotation) should be stated and justified. Aqueous media should be used where possible and sink conditions should be maintained. A small amount of surfactant may be added where necessary to control surface tension or for active ingredients of very low solubility. Buffer solutions should be used to span the physiologically relevant range—the current advice is over pH 1 6.8 or perhaps up to pH 8 if necessary. Ionic strength of media should be reported. The test procedure should employ six dosage forms (individually) with the mean data and a measure of variability reported. 

A very powerful method for the evaluation of solubility differences between polymorphs or solvates is that of intrinsic dissolution, which entails measurements of the rates of solution. One method for this work is to simply pour loose powder into a dissolution vessel, and to monitor the concentration of dissolved solute as a function of time. However, data obtained by this method are not readily interpretable unless they are corrected by factors relating to the surface area or particle size distribution of the powder. In the other approach, the material to be studied is filled into the cavity of a circular dissolution die, compressed until it exhibits the effective planar surface area of the circular disc, and then the dissolution rate is monitored off the surface of the rotating disc in the die [130],... 

This paper presents new data on dissolution kinetics. The effects of alkali concentration, size of the cation, and salt addition were studied. The influence of segmental mobility on dissolution was elucidated by measuring the temperature coefficients of the dissolution rates. Experiments were also carried out to study the relation between the chemical structure of a polymeric Inhibitor and Its effectiveness 1n retarding dissolution. Based on these results,... 

Once the diffusion coefficient is determined at a given concentration, the extent of fluorescence quenching can be predicted. Therefore, by working backward, one can determine the solvent diffusion coefficient and the solvent concentration in a polymer film from fluorescence quenching data. Consequently, if a polymer film dissolves in a solvent with a constant dissolution rate (DR), the solvent concentrations at different parts of the SCP can be determined. Finally, a SCP is constructed from these data. 

Fig. 5.16 Dissolution rate of 30% Ru02 + 70% Ti02 at 2 kA nrT2 in 300 g I-1 NaCI at 70°C arising from erosion and general dissolution (plotted from the data in Ref. [24]). 

The data in Figure 8 can be used to estimate the chemical dissolution rate on the surface of pore walls. For a PS with a density of 50% and an average pore diameter of 3 nm, the chemical dissolution rate is estimated to be about 6x10"4 A/s,... 

But within the pH range of natural waters, the dissolution (and precipitation) of carbonate minerals is surface controlled i.e., the rate of dissolution is rate determined by a chemical reaction at the water-mineral interface. Fig. 8.1 gives the data on the dissolution rates of various carbonate minerals in aqueous solutions obtained in careful studies by Chou and Wollast (1989). 

Stone (1987) proposes - in agreement with his experimental data - the following rate law for the dissolution rate ... 

Plummer, L. N., and F. T. Mackenzie (1974), "Predicting Mineral Solubility from Rate Data Application to the Dissolution of Magnesian Calcites", Amer. J. Sd. 274, 61 -83. 

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