Dissolution media, aqueous

Dissolution media, aqueous—See also Aqueous media and Aqueous processing... 

AIO.5.2.3.3 In preparing the transformation/dissolution medium, the pH of the medium should be adjusted to the desired pH (air buffering or CO2 buffering) by agitation for about half an hour to bring the aqueous medium into equilibrium with the buffering atmosphere. At least three samples (e.g. 10-15 ml) are drawn from the test medium prior to addition of the substance, and the dissolved metal concentrations are measured as controls and background. 

Occasionally salts may demonstrate lower aqueous solubilities and dissolution rates than expected due to the common ion effect. For example, the dissolution rate of doxycycline hydrochloride dihydrate salt was determined as four times greater in water than in O.IM HCl solution. Changing the dissolution medium from O.IM HCl to O.IM methanesul-fonic acid resulted in an increase in rate, clearly demonstrating specificity for chloride ions. This effect is due to the presence of chloride ions in the dissolution medium, which disturb the position of equilibrium for the drug solubilization process ... 

The dissolution rate of a drug substance is related to its aqueous solubility. For neutral drugs there is a direct correlation between the solubility and dissolution rate as demonstrated by the Noyes and Whimey equation (37.11). However, depending on the pH of the dissolution medium... 

The final nickel concentrations in Thomsen s experiments were quite high (approximately 0.14 m), thus applying a proper heat of dilution correction to determine Ar//°(V.63) is problematic [99ARC]. The final nickel concentrations in the experiments of Ashcroft [70ASH] and Gurrieri et al. [73GUR/CAL] were about a factor of five lower, but to use these values a correction for transfer of the aqueous species from the dissolution medium to water is needed. 

The nature of the dissolution medium can profoundly affect the shape of a dissolution profile. The relative rates of dissolution and the solubilities of the two polymorphs of 3-(3-hydroxy-3-methylbutylamino)-5-methyl-a5-triazino[5,6-Z)7indole were determined in USP artificial gastric fluid, water, and 50% ethanol solution [69]. In the artificial gastric fluid, both polymorphic forms exhibited essentially identical dissolution rates. This behavior has been contrasted in Fig. 6 with that observed in 50% aqueous ethanol, in which Form II has a significantly more rapid dissolution rate than Form I. If the dissolution rate of a solid phase is determined by its solubility, as predicted by the Noyes-Whitney equation, the ratio of dissolution rates would equal the ratio of solubilities. Because this type of behavior was not observed for this triazinoindole drug, the different effects of the dissolution medium on the transport rate constant can be suspected. 

Suitable manipulation of the dissolution medium can sometimes inhibit the conversion of one polymorph to another during the dissolution process, thus permitting the measurement of otherwise unobtainable information. In studies on the polymorphs of sulfathiazole and methylprednisolone, Higuchi, who used various alcohols and additives in the dissolution medium to inhibit phase transformations, first employed this approach [87], Aguiar and Zelmer were able to characterize thermodynamically the polymorphs formed by chloramphenicol palmitate and mefenamic acid by means of dissolution modifiers [88], Furthermore, the use of an aqueous ethanol medium containing 55.4%... 

Macheras et al.[56] used an automated FI on-line dialysis spectrophotometric system, incoiporating the dialyzer in a sample loop, to monitor the kinetic process of drug dissolution in low fat milk. The system is similar to that shown in Fig. 6.3, and the dissolution medium is circulated as donor stream through the dialyzer, pumping it from and back to the dissolution tank. Commercial formulations of salicylamide, propantheline bromide, nittbfurahtoin and acetaminophen were used in the study. The results show that the dissolution rate of drugs in milk are lower than in an aqueous buffer. 

The reactivity of titanium dioxide toward acids is very dependent on the temperature of the reaction mixture. It may be slowly dissolved by boiling concentrated sulfuric acid, with the dissolution rate being promoted by the addition of ammonium sulfate. Titanium dioxide may be readily dissolved by hydrofluoric acid. The material is completely insoluble in aqueous alkalies, but is readily dissolved in molten sodium (or potassium) hydroxide, carbonate, or borate. An equimolar molten mixture of sodium carbonate and sodium borate is partially effective as a dissolution medium. 

When the aqueous solubility of an active substance is too low, it can be dissolved in a different solvent or mixture of solvents, which is compatible with the route of administration. The solubility of a lipophilic substance (a substance which dissolves well in the oil or fat but poorly in water) can be increased by making the dissolution medium (water) less polar by the addition of less polar but water-miscible solvents. Often mixtures of water, ethanol and propylene glycol are used. Also glycerol and macrogol (polyethylene glycol) can be used. The polarity of a solvent can be expressed by its dielectric constant, e (for examples see Table 18.8, the higher the dielectric constant, the higher the polarity). 

Hypromellose or hydroxypropylmethylcellulose is a partly O-methylated and 0-(2-hydroxypropylated) cellulose [25]. It is used from 10% up to 80% w/w for controlled drug release in solid dosage form and from 2% to 20% w/w as coating solution for tablets and pellets [25,30,31 ]. Hydroxypropylmethylcellulose is a nonionic polymer with pH of a 2% w/w aqueous solution ranging from 5 to 8. It is soluble in water. Being nonionic, it will not form complexes with metallic salts or ionic compounds that can possibly lead to the precipitation of insoluble compounds [32]. Hydroxypropylmethylcellulose matrix hydrates and swells into a gel layer in the direction of matrix surfaces to core when it is contacted with the dissolution medium [14,20,33]. Erosion of gel takes place thereafter and may occur simultaneously with the subsequent phases of matrix hydration and swelling [14]. The swelling and erosion properties of a solid matrix made of... 

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