Dissolution rate characterization

Fig. 5.54 Mixed potential. (A) Zinc dissolution in acid medium. The partial processes are indicated at the corresponding voltammograms. (B) Dissolution of mercury in nitric acid solution. The original dissolution rate characterized by (1) the corrosion current y a is enhanced by (2) stirring which causes an...

In a detailed study the dissolution kinetics of shock-modified rutile in hydrofluoric acid were carefully studied by Casey and co-workers [88C01], Based on the defect studies of the previous sections in which quantitative measures of point and line defects were obtained, dissolution rates were measured on the as-shocked as well as on shocked and subsequently annealed powders. At each of the annealing temperatures of 200, 245, 330, 475, 675, 850, and 1000 °C, the defects were characterized. It was observed that the dissolution rates varied by only a factor of 2 in the most extreme case. Such a small effect was surprising given the very large dislocation densities in the samples. It was concluded that the dissolution rates were not controlled by the dislocations as had been previously proposed. 

It should be noted however that it is almost impossible to predict fully the in vivo dissolution rate due to the many factors involved, of which several have not yet been completely characterized. The introduction of new study techniques to directly follow drug dissolution in vivo in the human intestine should therefore be of importance [30, 31]. For example, in vivo dissolution studies discriminated between the dissolution rates of the two different particle sizes of spironolactone, based on the intestinal perfusate samples. In addition, dissolution rates of carba-mazepine obtained in vitro were significantly slower than the direct in vivo measurements obtained using the perfusion method. The higher in vivo dissolution rate was probably due to the efficient sink conditions provided by the high permeability of carbamazepine [30, 31]. 

While batch dissolution methods are simple to set up and to operate, are widely used, and may be carefully and reproducibly standardized, they suffer from the following disadvantages (1) the hydrodynamics are usually poorly characterized, with the notable exception of the rotating disc method, (2) a small change in dissolution rate will often create an undetectable and therefore an immeasurable perturbation in the dissolution time curve, and (3) the solute concentration cb may not be uniform throughout the solution volume V. 

The weathering of silicates has been investigated extensively in recent decades. It is more difficult to characterize the surface chemistry of crystalline mixed oxides. Furthermore, in many instances the dissolution of a silicate mineral is incipiently incongruent. This initial incongruent dissolution step is often followed by a congruent dissolution controlled surface reaction. The rate dependence of albite and olivine illustrates the typical enhancement of the dissolution rate by surface protonation and surface deprotonation. A zero order dependence on [H+] has often been reported near the pHpzc this is generally interpreted in terms of a hydration reaction of the surface (last term in Eq. 5.16). 

As was mentioned in the introduction to this chapter "diffusion-controlled dissolution" may occur because a thin layer either in the liquid film surrounding the mineral or on the surface of the solid phase (that is depleted in certain cations) limits transport as a consequence of this, the dissolution reaction becomes incongruent (i.e., the constituents released are characterized by stoichiometric relations different from those of the mineral. The objective of this section is to illustrate briefly, that even if the dissolution reaction of a mineral is initially incongruent, it is often a surface reaction which will eventually control the overall dissolution rate of this mineral. This has been shown by Chou and Wollast (1984). On the basis of these arguments we may conclude that in natural environments, the steady-state surface-controlled dissolution step is the main process controlling the weathering of most oxides and silicates. 

Different modifications of hydrous oxides, even if present in solution with the same surface area concentrations, are characterized by significantly different reactivities (e.g., dissolution rate). This depends above all on the different coordination geometry of the surface groups. For a given pH (on surface protonation) the reactivity of a Fem-center is likely to increase with the number of terminal ligands (Wehrli et al., 1990), i.e., groups such as -Fe-OH are less acid and react faster than... 

Anderberg, E.K., and Nystrom, C. (1990), Physicochemical Aspects of Drug Release X. Investigation of the Applicability of the Cube Root Law for Characterization of the Dissolution Rate of Fine Particulate Materials, Intemat. J. of Pharma., 62, 143-151. 

This section considers aspects and examples of the dissolution behaviour of individual iron oxides. Additional data are listed in Table 12.3 for a range of experimental conditions. As yet, characteristic dissolution rates carmot be assigned to the various iron oxides (Blesa Maroto, 1986). There are, however, some consistent differences between oxides with considerable stability differences, hence a comparison of the oxides is included here. In addition, the reactivity of any particular oxide may vary from sample to sample, depending on its source (natural or synthetic) and the conditions under which it formed. To illustrate this. Table 12.4 summarizes conditions and results from dissolution experiments in which a range of samples of the same oxide was compared. How the properties of the sample influence its dissolution behaviour is still not fully understood. A thorough characterization of the samples by solid state analysis, e. g. by EXAFS, to provide a basis for understanding the dissolution behaviour is, therefore, desirable. 

Examination of Figure 1-12 provides some clue to qualitatively gauge the interface reaction rate for reactions in water. Figure 1-12 shows that, for mineral with low solubility and high bond strength (characterized by (z+z )max, where z+ and z are valences of ions to be dissociated), the overall dissolution rate is controlled by interface reaction otherwise, it is controlled by mass transport. Because diffusivities of common cations and anions in water do not differ much (by less than a factor of 10 Table l-3a), when the overall reaction rate is controlled by interface reaction, it means that interface reaction is slow when the overall reaction rate is controlled by mass transport, the interface reaction rate is rapid. Therefore, from Figure 1-12, we may conclude that the interface reaction rate increases with mineral solubility and decreases with bond strength (z+z )max to be dissociated. 

By the above definition, b is positive for crystal dissolution, and negative for crystal growth. During convective crystal dissolution, the dissolution rate u is directly proportional to b. During diffusive crystal dissolution, the dissolution rate is proportional to parameter a, which is positively related to b. Hence, for the dissolution of a given mineral in a melt, the size of parameter b is important. The numerator of b is proportional to the degree of undersaturation. If the initial melt is saturated, b = 0 and there is no crystal dissolution or growth. The denominator characterizes the concentration difference between the crystal and the saturated... 

Hecq, J., Deleers, M., Fanara, D., Vranckx, H., Amighi, K. (2005). Preparation and characterization of nanocrystals for solubility and dissolution rate enhancement of nifedipine. International Journal of Pharmaceutics, 299, 167-177. 

Level B Correlation A predictive mathematical model for the relationship between summary parameters that characterize the in vitro and in vivo time courses, e.g., models that relate the mean in vitro dissolution time to the mean in vivo dissolution time, the mean in vitro dissolution time to the mean residence time in vivo, or the in vitro dissolution rate constant to the absorption rate constant. 

The majority of characterized solvates are stoichiometric, with either water or organic solvents present in a Lxed ratio with the drug molecules. Glibenclamide was isolated as two nonsolvated polymorphs, a pentanol solvate, and a toluene solvate (Suleiman and Najib, 1989). Furosemide could form solvates with dimethylformamide or dioxane (Matsuda and Tatsumi, 1989). Haleblian and McCrone (1969) studied the solid forms of steroids, and found different dissolution rates for two monohydrates of Luprednisolone, a monoethanol and hemiacetone solvate of prednisolone and two monoethanolates and a hemichloroform solvate of hydrocortisone. Other solvents that have been reported to form solvates with drugs include methyl ethyl ketone, propanol, hexane, dimethylsulfoxide, acetonitrile, and pyridine. The potential toxicity concerns eliminate most of these from consideration as practical mechanisms of solubility enhancement for human therapeutics. 

The effects of surfactant on the solubility and dissolution rate of poorly soluble drugs are well characterized. In general, the surfactant increases both solubility and dissolution rate even if the increment in dissolution rate is less pronounced due to the low diffusivity of the drug loaded into the micelle [9-16]. 

Drug formulations are designed to provide an attractive, stable, and convenient method to use products. Conventional dosage forms may be broadly characterized in order of decreasing dissolution rate as solutions, solid solutions, suspensions, capsules and tablets, coated capsules and tablets, and controlled release formulations. 

Many techniques have been used to characterize the physical nature of solid dispersions. These include thermal analysis (e.g., cooling-curve, thaw-melt, differential scanning calorimetry and X-ray diffraction, microscopic, spectroscopic, dissolution rate, and thermodynamic methods) Usually, a combination of two or more methods is required to obtain a complete picture of the solid dispersion system. 

Simonelli, A.P. Mehta, S.C. Higichi, W.I. Dissolution rates of high energy sulphathiazole-povidone coprecipitates II characterization of form of drug controlling its dissolution rate via solubility studies. J. Pharm. Sci 1976,65 (3), 355-361. 

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