The solubility of a substance is affected not only by temperature but also by the presence of other solutes. Equilibrium constant chemical equil solubility product ch. The phsolubility profiles indicated a phmax ph of maximum solubility of. In the current experimental condition the henderson hasselbalch hh relationship was used to predict the phdependent solubility profiles of choosen drug at two temperatures.
In drug formulation it is well known that salts from basic. Using the mean dissolution values from both curves al each time interval, calculate the difference factor f 1 and similarity factor f 2 using the above equations. Salts and solubility 5 activities in pdf phet contribution. Experiences and surprises in logs measurements krisztina takacsnovak semmelweis university, budapest physchem forum 9 september 17, 2010. Jun 27, 2015 many mesalamine formulations employ a ph dependent release mechanism designed to maximize drug release in the colon. This lowers the hydroxide concentration and makes magnesium hydroxide more soluble. Pdf in the present study the solubilityph profiles of sibutramine free base and its hydrochloride salt were determined in the ph range.
Cefpodoxime proxetil cp is third generation cephalosporin antibiotic and. For example, when the pka of a drug is in the range of 35, solubility should be. Equilibrium constant chemical equil solubility product. In the initial step, the solute is removed attracted away from its crystal.
The study revealed that carvedilol exhibited a typical weak base phdependent solubility profile with a high solubility at low ph 545. Qureshi, solubility considerations for drug dissolution testing november 12, 2012 page 1 the gi tract at a given time. Decreasing the ph increases the solubility of sparingly soluble bases and basic salts. Below ph 8 the free papaverine base starts to convert to cationic form. Jan 24, 20 in this work, the solubilities of lidocaine, thiabendazole, and terfenadine and their salts were measured and modeled as a function of ph. Determine the dissolution profile of two products 12 units each of the test and reference products. S decreases solubility increases due to increase in the surface area. All substances presented in this work are derivatives of anthranilic acid. Knowledge of comparative solubility profiles of a base and its hydrochloride salt is important in selecting one form over the other for dosage form design. Description this has all the materials for using the simulation for 5 different activities that i used throughout the year in different units. Pdf solubilityph profiles of a free base and its salt.
The ph solubility profile of the test drug substance should be determined at 37 1c in aqueous media with a ph in the range of 17. It all involves the application of le chateliers principle. College of pharmacy, chitradurga, karnataka india abstract ofloxacin is a synthetic fluoroquinolone broad spectrum anti microbial agent used in the treatment of bacterial. It should be noted that apis may have different aqueous solubilities, high or low, but for dissolution testing purposes api must be freely highly. General treatment of ph solubility profiles of weak acids and bases and the effects of different acids on the solubility of a weak base. Solute pka, solvent ph, and solubility university of north. Concerning your issue about how to increase the dissolution profile of cefpodoxime proxetil tablets. Cefpodoxime proxetil cp is third generation cephalosporin antibiotic and has poor. The effect of ph on a weak acid a and a weak base b 3. Dissolution tests are conducted for solid oral products. For curves to be considered similar, f 1 values should be close to 0, and f.
Many weakly soluble ionic compounds have solubilities which depend on the ph of the solution. In addition, the solubility of simple binary compounds such as oxides and sulfides, both strong bases, is often dependent on ph. Investigation of solubility and dissolution of a free base. The ph solubility profile of the api should be determined at 37 1 c in. Combining both phdependent solubility and phdependent permeability in one diagram provides a phwindow. The solubility ph profile of mefenamic acid as well as the pka values at two temperatures, 298. The pka also increases with an increase of temperature. Beyond this saturation concentration, a solute cannot further dissolve in the amount of solvent provided. Many sparingly soluble compounds have solubilities that depend on ph. The composite solubility versus ph profile and its role in intestinal.
The body is equipped with physical and chemical means to maintain its ph within the physiological range. For example, the anion in many sparingly soluble salts is the conjugate base of a weak acid that may become protonated in solution. For example, the presence of an acid can have a major influence on the solubility of a substance. It is possible for some substances to dissolve in a higher concentration than could be attained at equilibrium, have increased solubility, and form supersaturated solutions. To calculate free ion concentration in a saturated solution. Formulation and evaluation of ofloxacin aqueous injection. Absorption of basic drugs was found to be a function of the whole solubilityph relationship rather than a single solubility value at ph 7. Moisture content showed negligible impact on the dissolution kinetics of cuo nps. Pdf study of phdependent drugs solubility in water researchgate. Solubility product equilibrium to write an expression for an equilibrium constant. Oral solution formulations are likely to be challenging due to poor aqueous solubility chewable orodispersible tablets may evoke a gritty mouth sensation due to low drug solubility in the mouth taste assessment needs to be performed to understand whether taste masking is required and help guide dosage form selection. Reliable solubility and dissolution data, also in biorelevant media such as fessif and fassif were available acat inbuilt physiological parameters such as ph, transit times, volume and bile salt concentration across the intestinal tract were used to simulate fasted and high calorie, highfat hfhc meal conditions. Solubility is a physical property, and values for the solubility of pure substances are found in the literature.
The solubility was modeled using the epcsaft equation of state. For this purpose ph dependent profile of drug were determined at temperature of 298. Solubility 1 % wv no dissolutionrelated absorption problem highly insoluble drug administered in small doses may exhibit good absorption unstable drug in highly acidic environment of stomach, high solubility and consequent rapid dissolution could result in a decreased bioavailability the solubility of every new drug must be. In contrast, the dissolution rate constant correlated with ph for ph solubility and dissolution rate constants of cuo np in two test soils ph 5. At around ph 3 the solubility of the hcl salt reaches a maximum. The effect of acidbase equilibria the solubility of salts. Solubility of titanium dioxide in cosmetic formulations spectrophotometric method with hydrogen peroxide 5 in order to compare the results obtained by the method of derivative spectrophotometry, sam ples have been analysed by the spectrophotome tric method with hydrogen peroxide after 68 days of incubation. The size of this window is directly proportional to the observed oral bioavailability.
General treatment of phsolubility profiles of weak acids and. The novelty of the present work is to show the effect of ph on the solubility in buffer solutions at two temperatures and ambient. Dissolution of commercially available mesalamine formulations. Acidic, basic, and amphoteric oxides and hydroxides. In the last section we considered the dissolving of ionic compounds in pure water. The ph solubility profile of a weak acid or base is shown to be a function of its pksp, pka, and uncharged species solubility.
In a basic solution, the concentration of hydroxide ion in solution is high. According to the hendersonhasselbach equation, the relationship between ph, pka, and relative concentrations of an acid and its salt is as follows. Increase the dissolution profile of cefpodoxime proxetil. The higher solubility of the mesylate salt at ph 25 is attributed to its higher solubility product ksp than that of the hydrochloride salt. A direct example is hydroxides since the ohion is directly involved in the equilibrium constant. The effects of ph on solubility chemistry libretexts. Solubility of pharmaceuticals and their salts as a function of ph. Effect of soil organic matter, soil ph, and moisture content. Formulation and evaluation of ofloxacin aqueous injection 1, t. The solubility of many compounds depends strongly on the ph of the solution. The aqueous solubilities of lidocaine and thiabendazole were measured in the ph range between 0.
Figure 6 shows the phequilibrium solubility profile for flu at 298. The solubilities of five sparingly soluble drugcompounds in water were measured at constant temperatures 298. These phdependent solubility differences lead to ph. Solubility considerations for drug dissolution testing and. If you want to download the materials in word for easy editing, look at the individual activitiy postings. Ssosolubility of ionized species ph of a substance is related to its pka and the concentration of the ionized and unionized forms of the substance. The phsolubility profile of the test drug substance should be. Increase the dissolution profile of cefpodoxime proxetil tablets. Other cases of ph dependence may not be quite so simple. What is the relationship between solubility and ph. The number of ph conditions for a solubility determination can be bas ed on the ionization characteristics of the test drug substance. Intrinsic solubility so the equilibrium solubility of the free acid or base form of an ionizable compound at a ph where it is fully unionized. The studies with two model bases, namely, tiaramide and papaverine, showed that, except during phase transition from a base to a salt or vice versa, the ph solubility profiles are identical whether a base or a salt are used.
In case of very rapidly dissolving products, dissolution profiles may be accepted as similar. Solubility classification and eligibility for biowaiver procedure. Above ph 8 there is a constant value for the solubility of the nonionized neutral base. The maximum solubility of the ph equilibrium solubility profile is limited by the solubility product. Dissolution profiles of the two formulations are considered similar if f. These controls of ph in healthy humans include respiration. Most of the apis demonstrated ph versus solubility profiles in line with. Safety assessment of zinc salts as used in cosmetics.
217 1405 432 392 1142 903 1518 633 1038 1355 356 502 1460 1275 1068 93 856 920 415 734 94 1036 779 1243 939 859 203 1402 893 1165 557 1262