Henderson-Hasselbalch equation drugs

Generally it is only the non-dissociated or unionised drug that is lipid-soluble and a drug s degree of ionisation depends on its dissociation constant (pA) and the pH of the environment in which it finds itself. For an acidic drug this is represented by the Henderson Hasselbalch equation as... 

Fig. 3.2 Solubility profiles log S-pH. The dashed curves, representing uncharged precipitate in equilibrium with solution of the drugs, were calculated by Henderson-Hasselbalch equations. The dotted horizontal lines are estimates of the solubility of the charged form of the drugs, using either actual data (naproxen) or estimates based on the sdiff 3-4 approximation (atenolol and...

Fig. 3.3 Solubility profiles of sparingly soluble drugs, based on data taken from Avdeef et al. [20]. The solutions consisted of robotically adjusted universal buffers, based on a mixture of Good buffers (see text), and contained 0.2 M KCl. The dashed lines were calculated by the Henderson-Hasselbalch equation and, as can be seen, did not accurately describe the solubility profiles. The solid curves were...

The most important shortcoming of GSE is that it is valid only for nonelectrolytes, whereas many drug compounds and compounds in screening libraries are acidic or basic. In this case the solubility is pH-dependent. If one assumes for simplicity s sake that the ionized form is infinitely soluble in water, then the Henderson-Hasselbalch equation can be used to calculate the solubility at a given... 

A base exists predominantly as the ionised form at pHpKa. Rearrangement of the Henderson-Hasselbalch equation gives the expressions for the fraction of unionised drug as a function of pH and pKa ... 

The Henderson-Hasselbalch equation is used to predict A, changes in pH as the concentrations of HC03 or CO2 are altered or B, the ionic forms of drugs. 

An important step in the understanding of partitioning phenomena is the ability to link between a drug molecule s pKa and its pH-dependent solubility. The major tool for this estimation has been, for the past 80 years, the Henderson-Hasselbalch equation [133]. The ionized fraction of a drug can be calculated for any pH value if its pKa is known [134], as follows ... 

The Henderson-Hasselbalch equation enables predicting of how small changes in the pH values of the intestinal chyme could affect the solubility of poorly water-soluble drugs and hence their partitioning into the enterocyte membrane and their intestinal absorption. 

Henderson-Hasselbalch equation 15. Antisense drugs target RNA. Why do they not target DNA ... 

This equation essentially describes the relationship between pH and the degree of ionization of weak acids and bases. When applied to drugs, the equation tells us that when pH equals the apparent equilibrium dissociation constant of the drug (pKJ, 50 percent of the drug will be in the unionized form and 50 percent will be in the ionized form (i.e., log[base/acid] = 0 and antilog of 0 = 1, or unity). Application of the Henderson-Hasselbalch equation can, therefore, allow one to mathematically determine the exact proportion of ionized and nonionized species of a drug in a particular body compartment if the pKa of the drug and the pH of the local environment are known. 

THE USE OF THE HENDERSON-HASSELBALCH EQUATION TO QUANTIFY THE DEGREE OF IONISATION OF A DRUG SPECIES... 

The majority of the pharmaceutical drugs are weak bases or weak acids. Among the marketed drugs, more than 75% are weak bases, 25% are weak acids, and 5% are nonionic [38]. Therefore, knowledge of pK i is useful for enhancing drug solubility and stability. The Henderson-Hasselbalch equation is used to describe the ionization of a weak acid or base ... 

Many drugs are weak acids or bases with one or several pKa values. According to the Henderson-Hasselbalch equation, the solubility of an acidic drug will depend on the pK and pH as... 

It is obvious from the above equilibrium that the ratio of ionic to nonionic form of the drug in the solution is controlled by the proton concentration, which is commonly represented by pH values (negative logarithm of proton concentration). Taking the negative logarithm of expression (12-2), the well-known Henderson-Hasselbalch equation could be obtained ... 

The average pH of saliva is 6.4. Because the un-ionized form of a drug is the lipid-soluble-diffusible form, the piifa of the drug plays an important role in its absorption across the lipid membranes of the oral mucosa. The degree of ionization of a drug at a specified pH can be calculated using the Henderson-Hasselbalch equation as follows ... 

When a weakly acidic or basic drug is administered to the body, the drug will ionise to a greater or lesser extent depending on its piCa and the pH of the body fluid in which it is dissolved. The pH of the body varies widely, but the most important biological solution is the blood, which, as stated above, normally has a pH of 7.4. An equation can be derived that will predict the extent to which the drug ionises, and, as is often the case, the starting point for the derivation is the Henderson-Hasselbalch equation (1.7). 

The acidity or basicity of a drug substance is defined by the dissociation constant K, which is the equilibrium constant, more conveniently represented by its logarithmic parameter pK, reflecting the degree of ionization of a substance at a particular pH and described by the Henderson-Hasselbalch equations (37.2) and (37.3). ... 

Much of the beneht in solubihty enhancement from salt formation is attributable to the change in solution pH caused by the presence of the counterion. This occurs because the ionization and solubility of acidic drugs (such as barbiturates and non-steroidal anti-inflammatory drugs) increases in basic conditions but decreases in acidic conditions. This behavior is exemplified by derivations of the Henderson-Hasselbalch equations (37.2) and (37.3). The opposite situation occurs for basic drugs such as chlorpromazine, morphine and codeine, which are more soluble in acidic conditions. 

The degree of drug ionization depends upon both the pH of the solution in which it is presented to the biological membrane and on the pKa (dissociation constant) of the drug (whether it is an acid or base). The entire concept of pKa is derived from the Henderson-Hasselbalch equation for both acids and bases as follows ... 

The cell membrane is lipophilic in nature, and therefore acts as a barrier to drugs that are water-soluble. Those drugs that are dissociated (charged) at physiologic pH for a particular compartment will not cross the lipophilic cell membrane, and will therefore not be absorbed, or will be absorbed in lesser quantities, which are predicted by the Henderson-Hasselbalch equation. 

Drugs that are weak acids exist in a protonated state within an acid environment, but when exposed to a basic environment, the proton dissociates, forming an anion and a cation (the molecule ionizes). The protonated (non-dissociated, non-ionized) state is thus the more lipophilic for a drug that is a weak acid. This becomes important when utilizing the Henderson-Hasselbalch equation to predict the degree of absorption across cell membranes. 

The pH of the tissue at the injection site will influence the potency of the drug. In order for the drug to enter the cell and bind to the cytoplasmic side of the sodium channel, it must be in nonionized form (see the Henderson-Hasselbalch equation, Chapter 1, General Pharmacology). The more ionized a drug is, the less potent it is. Thus, dosage must be increased in order to achieve maximal efficacy. 

WEAK ELECTROLYTES AND INFLUENCE OF pH Most drugs are weak acids or bases that are present in solution as both the hpid-soluble and diffusible nonionized form, and the relatively lipid-insoluble nondiffusible ionized species. Therefore, the transmembrane distribution of a weak electrolyte is determined by its pIsT (pH at which 50% is ionized) and the pH gradient across the membrane (see Figure 1-2). The ratio of nonionized to ionized drug at each pH is readily calculated from the Henderson-Hasselbalch equation ... 

FIGURE 1-2 Influence of pH on the partitioning of a weak acid (pK = 4.4) between plasma (pH = 7.4) and gastric juice (pH = 1.4) separated by a lipid barrier. The gastric mucosal membrane behaves as a lipid barrier permeable only to die lipid-soluble, nonionized form of the acid. The ratio of nonionized to ionized drug at each pH is readily calculated from die Henderson-Hasselbalch equation diat relates die pH of the medium and die drug s dissociation constant (p ) to the ratio of the protonated (HA) and unprotonated (A") forms. The same principles apply to drugs that are weak, bases (BH B -l- H ). 

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