Dissolution rate and solubility

The fundamentals of the measurements of solubility and dissolution properties of pharamceuticals are given elsewhere in considerable detail (Vachon and Grant 1987  

The rate and extent of the physiological absorption of an active drug substance are decisive factors in its overall efficacy (e.g. carbamazepine, Zannikos et al. 1991). These can vary among different crystal modifications, and they have become an important scientific and regulatory issue (Ahr et al. 2000). 

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Stucki, G., Alexander, M. (1987) Role of dissolution rate and solubility in biodegradation of aromatic compounds. Appl. Environ. Microbiol. 53, 292-297. 

Differences in solubility between different crystal forms alter the driving force for dissolution, controlled by the difference between the solution concentration and the saturation concentration (Cs - C). Hamlin et al. (1965) have shown that dissolution rate correlates well with solubility for a large number of pharmaceutical compounds varying in solubility from 0.01 to 10 mg/mD t 37 Nicklasson and Brodin (1984) have shown that using cosolvent mixtures fordrugs with poor aqueous solubility produces a good correlation between dissolution rate and solubility. 

Hamlin, W.E., Northam, J.I., and Wagner, J.G (1965). Relationship betvne itro dissolution rates and solubilities of numerous compounds representative of various chemical spdciSttarm. Sci., 54 1651-1653. 

Nicklasson, M. and Brodin, A. (1984). The relationship between intrinsic dissolution rates and solubilities in the water-ethanol binary systehif. J. Pharm., 18 149-156. 

Kuma K., Nakabayashi S., Suzuki Y., and Matsunaga K. (1992) Dissolution rate and solubility of colloidal hydrous ferric oxide in seawater. Mar. Chem. 38, 133-143. 

Many compounds form crystals with different molecular arrangements, or polymorphs. These polymorphs may have different physical properties, such as dissolution rate and solubility. The vitamin riboflavin exists in several polymorphic forms, and these have a 20-fold range in aqueous solubility. Polymorphs that have no crystal structure, or amorphic forms, have different physical properties from the crystalline forms. 

The combined effect of pH and surfactants on the dissolution of piroxicam has been reported. " In this system, the dissolution rate and solubility of the drug substance could be well estimated by a simple additive model for the effect of pH and surfactant, where the total dissolved concentration equaled the summation of the amoimt of dissolved non-ionized substance, the amount of dissolved ionized substance, and the amoimt of substance solubilized in the surfactant micelles. It was suggested that the model developed in this work could be useful in establishing an in vitro-in vivo correlation for piroxicam. 

Polymorphism is the ability of a chemical species to crystallize in more than one distinct crystal habit. The pharmaceutical applications of polymorphism have been reviewed by several authors. The differences in dissolution rate and solubility that polymorphs can produce may have a dramatic impact on bioavailability when dissolution is the rate-limiting step in the absorption process. 

Polymorphic form also influences dissolution rate and solubility. By definition, metastable polymorphs should have higher solubility and faster dissolution rates than those of their more stable crystalline counterparts because they possess a higher Gibbs free energy. Generally, only a moderate enhancement of solubility and dissolution rate can be achieved through polymorphic modification, although... 

The dissolution rate and solubility in a solvent medium are two of the most important characteristics of a drug substance, because these quantities determine the bioavailability of the drug for its intended therapeutic use. Solubility is defined as the equilibrium concentration of the dissolved solid (the solute) in the solvent medium and is ordinarily a function of temperature and pressure. 

Ultimately calcite dissolution rate and solubility depend on pH values, which in the natural water are closely associated with the CO content. For this reason calcite usually dissolves until it reaches certain equilibrium with the content or partial pressure of CO. ... 

Overall, the dissolution rate and solubility of minerals with diffuse-kinetic dissolution regime change within a broad range of values and depend on water acidity. These minerals are preserved for quite a long time under surface conditions even in humid climate. Their dissolution is the cause of most common on the surface carbonate karst. 

Minerals with Kinetic Dissolution Condition Minerals of this group are considered in everyday life insoluble. Ihey include mostly metal oxides, hydroxides, sulphides and aluminum sihcates. The mechanism of their dissolution is dominated by hydrolysis whose nature depends on the structure and composition of minerals. Their dissolution under any conditions has kinetic condition, i.e., it is controlled by extremely slow chemical reactions of surface complexation. The rate of their dissolution is noticeably lower than 10 ° mole m s and the solubility does not exceed 10" mole l Besides, both their dissolution rate and solubility depend on pH values. These minerals are most common in the Earth crust and often play a leading role in the formation of imderground water composition. It is convenient to subdivide minerals with kinetic dissolution regime into three groups 1- silica, 2 - oxides, hydroxides and sulphides of metals, 3-aluminum silicates. 

On the whole, correlations of the dissolution rate and solubility vs. pH values are similar, which shows in their increase in alkaline water. 

Comparison of the dissolution rates and solubilities for individual minerals demonstrates a surprising similarity of these correlations with the pH value. As a regular rule, with max solubility is associated max dissolution rate. 

Dissolution rate and solubility of the fendiline-base- /3-cyclodextrin /F- (iCD/ complex at the pH of the gastric juice is much higher than those of the presently marketed fendiline hydrochloride /F HCl/ The X-labelled F HC1 and F- (iCD jeTe orally administered to rats in a dose 5 in /kg and the activity of the blood, serum, urine and faeces was detected for 48 h ... 

As acidic and basic drugs demonstrate pH-dependent solubility, their dissolution rates in aqueous media having different pH values may differ greatly. The Noyes-Whitney equation describing the relationship between dissolution rate and solubility (Noyes and Whitney 1897) is given below ... 

All of the examples discussed in Section 7.2.3, reveal the great potential of solid forms that can be exploited to achieve the desired pharmacokinetic properties. However, one has to also keep in mind the possibility that an increase in dissolution rate and solubility could sometimes even prove to be detrimental. It could lead to the accumulation of the drug, beyond the equilibrium solubility, creating a driving force for the nucleation and crystallization of some stable phases in the physiological medium. To avoid any such accumulation, the drug should possess a sufficient absorption rate for its optimal distribution in the body. 

Figure 7.5(a) Ratio of dissolution rates and solubilities of sulphamethizole in surfactant solution to those in distilled water, (b) Ratio of dissolution rates and solubilities of sulphadiazine in surfactant solution to those in distilled water. 

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