Dissolution rate/time

Two observations relevant to ECM can be made. (/) Because the anode metal dissolves electrochemicaHy, the rate of dissolution (or machining) depends, by Faraday s laws of electrolysis, only on the atomic weight M and valency of the anode material, the current I which is passed, and the time t for which the current passes. The dissolution rate is not infiuenced by hardness (qv) or any other characteristics of the metal. (2) Because only hydrogen gas is evolved at the cathode, the shape of that electrode remains unaltered during the electrolysis. This feature is perhaps the most relevant in the use of ECM as a metal-shaping process (4). 

It would seem easy in principle to separate cracking that proceeds by anodic dissolution from hydrogen-assisted cracking by investigating the effects of polarisation on the crack growth rate, time to failure or some... 

Nevertheless, it was clearly shown [453] that diy extended milling efficiently increases the dissolution rate of the material. Thus, a powder milled for 50 hours exhibits a dissolution rate 4500 times higher than a powder after only two hours of milling. 

In addition to these in vitro demonstrations of the importance of the effective surface area of drug particles on dissolution rate, many in vivo studies are available. Phenacetin plasma levels versus time are plotted for three different particle sizes of phenacetin in Fig. 14. Healthy adult volunteers received 1.5-g doses of phenacetin as an aqueous suspension on an empty stomach. The results show that both the rate and... 

Figure 3 illustrates a situation in which this may not be true. When 250 mL of water was taken with erythromycin tablets, the extent of absorption was much greater than when the tablets were taken with only 20 mL of water. In the latter case, dissolution probably did not occur under sink conditions. Hence, the dissolution rate decreased, and it appears that not all of the erythromycin had a chance to dissolve in the GIT. Note than the dissolution was not, however, the ratedetermining step in absorption, since the time to reach the peak concentration was the same in all situations. 

Determination of the time for a tablet to disintegrate when immersed in some test fluid has been a requirement in most compendia for many years. For many years, it was the only test available to evaluate the release of medicaments from a dosage unit. We now recognize the severe limitations of such tests in assessing this property—hence, the introduction of dissolution rate requirements. 

Interestingly, exceptions are possible. Stewart et al. [81] reported that the effect of magnesium stearate concentration on the dissolution of a model low-dose drug, riboflavin, from capsules was dependent in some manner on the type of filler. Soluble fillers exhibited the anticipated prolonged times with increasing lubricant levels. However, the trends with insoluble fillers were less predictable. In some cases insoluble fillers were only slightly affected by the concentration of magnesium stearate. For others, such as microcrystalline cellulose, there appeared to be an ideal intermediate concentration of lubricant at which the dissolution rate was maximized. 

This aromatic alcohol has been an effective preservative and still is used in several ophthalmic products. Over the years it has proved to be a relatively safe preservative for ophthalmic products [138] and has produced minimal effects in various tests [99,136,139]. In addition to its relatively slower rate of activity, it imposes a number of limitations on the formulation and packaging. It possesses adequate stability when stored at room temperature in an acidic solution, usually about pH 5 or below. If autoclaved for 20-30 minutes at a pH of 5, it will decompose about 30%. The hydrolytic decomposition of chlorobutanol produces hydrochloric acid (HC1), resulting in a decreasing pH as a function of time. As a result, the hydrolysis rate also decreases. Chlorobutanol is generally used at a concentration of 0.5%. Its maximum water solubility is only about 0.7% at room temperature, which may be lowered by active or excipients, and is slow to dissolve. Heat can be used to increase dissolution rate but will also cause some decomposition and loss from sublimation. Concentrations as low as 0.125% have shown antimicrobial activity under the proper conditions. 

Since dosage forms contain more than just active drug, it is of practical interest to understand how the various components from a multicomponent solid influence their own dissolution and release. Nelson [18] was one of the first pharma-ceuticists to ponder this question and perform the initial dissolution studies. Unfortunately, Nelson initially considered the dissolution of interacting solids (benzoic acid + trisodium phosphate), which is a more complicated and more complex situation than simple multicomponent dissolution of noninteracting solids. Nelson did show that for his benzoic acid and trisodium phosphate pellets, there was a maximum increase in benzoic acid dissolution in water at a mole fraction ratio of 2 1 (benzoic acid trisodium phosphate) and that the benzoic acid dissolution rate associated with the maximum rate was some 40 times greater than that of benzoic acid alone. 

Fig. 1.4 The calculated results for one acoustic cycle when a bubble in water at 3 °C is irradiated by an ultrasonic wave of 52 kHz and 1.52 bar in frequency and pressure amplitude, respectively. The ambient bubble radius is 3.6 pm. (a) The bubble radius, (b) The dissolution rate of OH radicals into the liquid from the interior of the bubble (solid line) and its time integral (dotted line). Reprinted with permission from Yasui K, Tuziuti T, Sivaknmar M, Iida Y (2005) Theoretical study of single-bubble sonochemistry. J Chem Phys 122 224706. Copyright 2005, American Institute of Physics...

The absorption of class III drugs is limited by their permeability over the intestinal wall. Thus, as this process is not at all modeled by the classical in vitro dissolution test, no IVIVC should be expected. When drug dissolution becomes slower than gastric emptying, a reduction in the extent of bioavailability will be found in slower dissolution rates as the time when the drug is available for permeation over the gut wall in the small intestine will then be reduced. Thus, the same type of relationship can be expected between bioavailability and in vitro dissolution, as shown in Fig. 21.12 for a class I drug. 

One approach to the study of solubility is to evaluate the time dependence of the solubilization process, such as is conducted in the dissolution testing of dosage forms [70], In this work, the amount of drug substance that becomes dissolved per unit time under standard conditions is followed. Within the accepted model for pharmaceutical dissolution, the rate-limiting step is the transport of solute away from the interfacial layer at the dissolving solid into the bulk solution. To measure the intrinsic dissolution rate of a drug, the compound is normally compressed into a special die to a condition of zero porosity. The system is immersed into the solvent reservoir, and the concentration monitored as a function of time. Use of this procedure yields a dissolution rate parameter that is intrinsic to the compound under study and that is considered an important parameter in the preformulation process. A critical evaluation of the intrinsic dissolution methodology and interpretation is available [71]. 

The magnitude of association between a drag compound and various cyclodextrins depends critically on the details of the fit of the substrate into the cyclodextrin cavity. As shown in Table 6, the experimental compound RS-82856 forms the strongest complexes with /3-cyclodextrin, while maximal solubility is reached with y-cyclodextrin [62], Formation of the /8-cyclodextrin complex dramatically increased the dissolution rate of the compound as well. For RS-82856 itself, 20% dissolved within 20 minutes, while more than 80% of the drug-/3-cyclodextrin complex was found to be dissolved at the same time point. 

The dissolution rate of a solid may be defined as dm/dt, where m is the mass of solid dissolved at time t. In a batch dissolution method, the analyzed concentration, cb, in the solution (if well stirred) is representative of the entire volume, V, of the dissolution medium, so that... 

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. 

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