Benzoic acid, dissolution

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. 

Thus the benzoic acid dissolution does take place in a short pipe, where short is defined in terms of diffusion. 

R Braun, E Parrot. Effect of various parameters upon diffusion-controlled dissolution of benzoic acid. J Pharm Sci 61 592, 1972. 

Table 1 lists experimental results from HPWH s original paper [2] in which the dissolution of benzoic acid tablets in aqueous sodium hydroxide solutions was measured gravimetrically. Results from other dissolution experiments in acetate, phosphate, carbonate, and tetraborate buffers, where agreement between theory and experiment were comparable to those listed in Table 1, established this paper and the theoretical HPWH model as the premier reference for dissolution with reaction in pharmaceutics in the 1960s and throughout the 1970s. 

Figure 5 Dissolution rates of salicylic acid-benzoic acid mixtures. ( ) Benzoic acid from melt (O) salicylic acid from melt (A) salicylic acid from mechanical mix ( ) Benzoic acid from mechanical mix. (From Ref. 19.)... 

Evidence for the formation of (188) is provided by the observation that while dissolution of unhindered benzoic acid itself (189) in cone. H2S04 results in the expected two-fold freezing point depression ... 

Work on the rate of dissolution of regular shaped solids in liquids has been carried out by Linton and Sherwood(1), to which reference is made in Volume 1. Benzoic acid, cinnamic acid, and /3-naphthol were used as solutes, and water as the solvent. For streamline flow, the results were satisfactorily correlated on the assumption that transfer took place as a result of molecular diffusion alone. For turbulent flow through small tubes cast from each of the materials, the rate of mass transfer could be predicted from the pressure drop by using the 1 j-factor for mass transfer. In experiments with benzoic acid, unduly high rates of transfer were obtained because the area of the solids was increased as a result of pitting. 

Benzoic acid is assayed by titration with 0.1 N sodium hydroxide VS to a pink phenolphthalein endpoint. The procedure calls for the dissolution of about 500 mg of accurately weighed sample in 25 mL of diluted alcohol (previously neutralized with 0.1 N sodium hydroxide). Each milliliter of 0.1 N sodium hydroxide is equivalent to 12.21 mg of benzoic acid. 

Lepidocrocite (-y-FeOOH) has also been used as a catalyst for Fentonlike reactions [54]. First-order decomposition of hydrogen peroxide was observed in the presence of this catalyst. Peroxide decay at 20 g/L catalyst was found to be pseudo-first-order and pH-dependent, with rate constant values reported from 0.102 hr-1 at pH 3.3 to 0.326 hr-1 at pH 8.9. In this system benzoic acid degradation was fastest at the low pH value. Under these conditions, acid dissolution of the lepidocrocite was observed to produce... 

Noyes and Whitney published [103] in 1897 the first quantitative study of a dissolution process. Using water as a dissolution medium, they rotated cylinders of benzoic acid and lead chloride and analyzed the resulting solutions at various time points. They found that the rate c(t) of change of concentration c (t) of dissolved species was proportional to the difference between the saturation solubility cs of the species and the concentration existing at any time t. Using... 

In a batch slurry reactor, the liquid-solid mass-transfer coefficient can be measured by dissolving a sparingly soluble solid in liquid. The concentration of dissolved solid in liquid (Bt) can be measured as a function of time, preferably by a continuous analytical device. Systems such as the dissolution of benzoic acid, jS-naphthol, naphthalene, or KMn04 in water can be used. A plot of B( as a function of time and the slope of such plot at time t = 0 can give ks as... 

Carboxylic acids are conveniently utilized in the extraction of a number of metal ions. The dissolution of metal soaps in trichlorobenzene was first noticed by Biffen and Snell (12). The first example of the liquid-liquid extraction involving a metal carboxylate appears to be the extraction of scandium with benzoic acid prior to the colorimetric determination (54). 

The liquid-solid mass-transfer coefficient under trickle-flow conditions was first measured by Van Krevelen and Krekels102 from the rate of dissolution of benzoic acid with no gas flow. They presented a relation... 

That the rate-controlling process might change with conditions has been realized since the early days of the Nernst theory. For example at high stirring speeds the surface process might be slower than convective transport. In 1909 Wilderman (32) reported that benzoic acid reached a maximum dissolution rate but examination of his data shows that the... 

Childs et al. formulated crystalline complexes with a salt form of an API with carboxylic acids. The antidepressant, fluoxetine hydrochloride, was cocrystallized with benzoic acid, succinic acid, and fumaric acid where the chloride ion acts as a hydrogen bond acceptor for the carboxylic acid groups of the three ligands. Intrinsic dissolution studies were carried out at 10°C because at 25°C, the rates were so rapid that the dissolution rates of the cocrystals could not be distinguished from one another. The fumaric acid 2 1 complex had a similar dissolution rate to that of the crystalline fluoxetine hydrochloride, but the dissolution rate for the benzoic acid 1 1 complex was half that of fluoxetine hydrochloride. Fluoxetine hydrochloride succinic acid 2 1 complex had approximately three times higher dissolution rate, but the dissolution was so fast that an accurate value was difficult to measure. ... 

Serajuddin, A.T.M. Jarowski, C.I. Effect of diffusion layer 54. pH and solubility on the dissolution rate of pharmaceutical acids and their sodium salts. II. Salicylic acid, theophylline and benzoic acid. J. Pharm. Sci. 1985, 74 (2), 148-154. 55. 

Add benzoic acid (10 g, 82 mmol) to the organic extracts and stir with a glass rod to ensure complete dissolution ofthe acid. 

When a solution of, for example, benzoic acid is prepared by dissolving a given number of mol in a specific volume of solution, the concentration is given as number of mol/volume of solution. When a concentration is worked out in this way, i.e. in terms of what was weighed out, it is called the stoichiometric concentration. But what really is of interest is what is actually present in solution, and a concentration based on this is called the actual concentration. If, on dissolution, the solute is involved in any reaction or equilibrium, then the stoichiometric concentration will not correspond to what is actually present. 

In a subsequent study, Linton and Sherwood (1950) extended the range of Schmidt number when they investigated the rate of dissolution of benzoic acid, cinnamic acid, and -naphthol. The combined results were correlated by... 

As discussed in 9.10.2, the calculation of the mass transfer coefficient fiat requires knowledge of the value of the dissipation energy e. It can be calculated at different stirring rates and liquid loads by measuring the dissolution rates of some solid materials, for instance, benzoic acid. 

Fig. 9.18. The pH-dependent dissolution of salicylic acid (o), benzoic acid ( ), and phenobarbital ( ). (From Gibaldi M. Biopharmaceutics and Clinical Pharmacokinetics, 4th Ed. Philadelphia Lea and Febiger, 1991, with permission.)...

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