Crystalline salts dissolution rate

While the metastable forms offer higher dissolution rates, many manufacturers use a particular amorphous, crystalline, salt, or ester form of a drug with the solubility needed to be dissolved in the established conditions, for instance, to prepare a chloramphenicol ophthalmic solution [39]. Thus, the selection of amorphous or crystalline form of a drug may be of considerable importance to facilitate the formulation, handling, and stability [37]. 

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. ... 

When the solvate happens to be water, these are called hydrates, wherein water is entrapped through hydrogen bonding inside the crystal, and strengthens the crystal structure, thereby invariably reducing the dissolution rate (Table 4). The water molecules can reside in the crystal either as isolate lattice, where they are not in contact with each other as lattice channel water, where they fill space and metal coordinated water in salts of weak acids, where the metal ion coordinates with the water molecule. Metal ion coordinates may also fill channels, such as in the case of nedocromil sodium trihydrate. Crystalline hydrates have been classified by structural aspects into three classes isolated lattice sites, lattice channels, and metal-ion coordinated water. There are three classes, which are discernible by the commonly available analytical techniques. 

The factors described earlier that affect the solubility of a lead compound when choosing a particular salt form—a polymorphic form—a specific crystalline form directly affects the most critical parameter that determines the drug activity, which is the dissolution rate in the biological milieu. The first step in the commencement of dissolution is the wettability of solid particles—there is a direct correlation between wettability and bioavailability. As the milieu of drug administration sites is mostly aqueous in nature, low wettability makes the particles less hygroscopic. 

The preparation of salts is frequently undertaken to improve the physicochemical properties of an ionizable compound. Most often, improvement of solubility and dissolution rate is desired. However, improvement in crystallinity (e.g., melting point), stability, or hygro-scopicity may be possible (1,2). Figure 18.1 shows the solubility of several salts of terfena-dine and the free base as a function of pH. Development of salts, particularly soluble salts of insoluble compounds, is not without challenge, however. Complete characterization of salt forms is needed (4). If the salt is very soluble, precipitation of the insoluble free base (or free acid) may occur in uivo under physiological pH conditions. 

The effect of the mineral is determined first of all by its strength, i.e., energy of its crystalline lattice. Max dissolution rate belongs with salts of strong adds and bases (alkali), with the weakest crystalline lattice and max solubility. The lowermost rate is observed at hydrolysis solution of minerals with strong crystalline lattice. 

Silver nitrate in ammoniacal solution may be completely reduced to silver by aqueous arsenious oxide. The reduction is hindered by the presence of ammonium sulphate, owing to the decrease in concentration of the hydroxyl ions 5 neutral salts such as sodium sulphate or sodium nitrate have no effect. Similarly, auric chloride may be reduced to gold.6 At 20° C. an aqueous solution of vitreous arsenious oxide reacts 4 to 5 times as rapidly as an aqueous solution of the octahedral form 7 the greater rate of dissolution in water of the former variety has been mentioned (p. 137), but from supersaturated solutions of the two forms there is no appreciable difference in the rates of deposition. The explanation of the inferior reducing power of the crystalline variety may be that there exist anisotropic molecules which only slowly lose their anisotropic properties. An ammoniacal solution of arsenious oxide heated with cupric sulphate in a sealed tube at 100° C. causes reduction... 

---