Chapter 8, Problem 8.54AP

Interpretation Introduction

(a)

Interpretation:

The drug which has greater partition coefficient is to be stated.

Concept introduction:

The partition coefficient is defined as the ratio of the concentration of the compound in two different solvents. The octanol-water partition coefficient is one of the most used partition coefficients which is the ratio concentration in octanol to the water.

$P_{\text{ow}}=\frac{\text{drug concentration in 1-octanol phase}}{\text{ drug concentration in water phase}}$

Answer to Problem 8.54AP

The $\left(S\right)\text{-}$ prorpanolol has the greater partition coefficient because of being the most non-polar among two drugs.

Explanation of Solution

The structure of the two drugs is shown below.

Figure 1

From the structure of two drugs, it is clear that $\left(S\right)\text{-}$ atenolol contains more number of polar groups and also hydrophobic groups present in it lesser than the $\left(S\right)\text{-}$ propranolol Octanol is a non-polar solvent and water is a polar solvent. The polar compounds are more soluble in water than octanol.

Therefore, the partition coefficient of $\left(S\right)\text{-}$ propranolol is more than $\left(S\right)\text{-}$ atenolol because it is less polar and its concentration will be more in the octanol solvent.

Conclusion

The $\left(S\right)\text{-}$ propanolol has the greater partition coefficient because it is more nonpolar drug.

Interpretation Introduction

(b)

Interpretation:

The concentration of atenolol in each phase is to be stated.

Concept introduction:

The partition coefficient is defined as the ratio of the concentration of the compound in two different solvents. The octanol-water partition coefficient is one of the most used partition coefficients which is the ratio concentration in octanol to the water.

$P_{\text{ow}}=\frac{\text{drug concentration in 1-octanol phase}}{\text{ drug concentration in water phase}}$

Answer to Problem 8.54AP

The amount of atenolol is $0.376\text{g}$ and in octanol is $0.624$.

Explanation of Solution

The given value of the logarithm of the partition coefficient is shown below.

$\text{log}{P}_{\text{ow}}=0.22$

Take antilog on both sides to find out value of $P_{\text{ow}}$ as shown below.

$\begin{array}{rll}{P}_{\text{ow}}& =& {10}^{0.22}\\ & =& 1.66\end{array}$

The formula of the partition coefficient is shown below.

$P_{\text{ow}}=\frac{\text{drug concentration in 1-octanol phase}}{\text{ drug concentration in water phase}}$

Substitute the value of $P_{\text{ow}}$ in above equation as shown below.

$\begin{array}{rll}1.66& =& \frac{\text{drug concentration in 1-octanol phase}}{\text{ drug concentration in water phase}}\\ 1.66\times \text{drug concentration in water phase}& =& \text{drug concentration in 1-octanol phase}\end{array}$

The concentration of drug in octanol is $1.66$ times than the water.

Since the volume of each phase is given same.

Therefore, the ratio of amount of atenolol in octanol to water is $1.66:1$.

Assume x to be the ratio constant to find out the amount in each solvent. Therefore, the amount of atenolol in water is x and in octanol is $\text{1}\text{.66x}$.

The sum of both amounts is equal to the total amount.

$\begin{array}{rll}1.66\text{x}+\text{x}& =& \text{1}\text{.0}\text{g}\\ \text{2}\text{.66x}& =& \text{1}\text{.0}\text{g}\\ \text{x}& =& \frac{\text{1}\text{.0}\text{g}}{2.66}\\ & =& 0.376\text{g}\end{array}$

Therefore the amount of atenolol is $0.376\text{g}$ and in octanol is $0.624\left(1.66\times 0.376=0.624\right)$.

Conclusion

The amount of atenolol is $0.376\text{g}$ and in octanol is calculated as $0.624$.

Interpretation Introduction

(c)

Interpretation:

The relative water solubility’s of the crystalline atenolol and propranolol are to be stated.

Concept introduction:

The partition coefficient is defined as the ratio of the concentration of the compound in two different solvents. The octanol-water partition coefficient is one of the most used partition coefficients which is the ratio concentration in octanol to the water.

$P_{\text{ow}}=\frac{\text{drug concentration in 1-octanol phase}}{\text{ drug concentration in water phase}}$

Answer to Problem 8.54AP

The $\left(S\right)\text{-}$ atenolol has higher water solubility than the $\left(S\right)\text{-}$ propranolol.

Explanation of Solution

From the structure of two drugs, it is clear that $\left(S\right)\text{-}$ atenolol contains more number of polar groups and also hydrophobic groups present in it are lesser than the $\left(S\right)\text{-}$ propranolol. Octanol is a non-polar solvent and water is a polar solvent. The polar compounds are more soluble in water than octanol.

Therefore, the partition coefficient of $\left(S\right)\text{-}$ propranolol is more than $\left(S\right)\text{-}$ atenolol because it is less polar and its concentration will be more in the octanol solvent.

That means $\left(S\right)\text{-}$ atenolol is more soluble in water as compared to $\left(S\right)\text{-}$ propranolol.

Conclusion

The $\left(S\right)\text{-}$ atenolol has higher water solubility than the $\left(S\right)\text{-}$ propranolol because the $\left(S\right)\text{-}$ propanolol has the greater partition coefficient value.

Interpretation Introduction

(d)

Interpretation:

The structure of the conjugated acids of the both drugs is to be drawn.

Concept introduction:

The drugs $\left(S\right)\text{-}$ propranolol and $\left(S\right)\text{-}$ atenolol both contains a basic amino group in their structure. The amino group is basic and it accepts a proton in its acid-base reaction. The conjugate acid of amino group contains the protonated amino group.

Answer to Problem 8.54AP

The structure of the conjugated acids of the both drugs is shown below.

Explanation of Solution

The structure of conjugate acids of both drugs can be made by protonating the amino groups of each drug.

The structures of conjugate acids of each drug are shown below.

Figure 2

Conclusion

The structure of the conjugated acids of the both drugs is shown in Figure 2.

Interpretation Introduction

(e)

Interpretation:

An explanation about the change in the partition coefficient of each drug if it was determined again using water of $\text{pH }7.4$ is to be stated.

Concept introduction:

$\text{p}{K}_{\text{a}}$ of the acid represents the $\text{pH}$ at which the acid will be found in the protonated form or dissociated form. The acid is found in the dissociated form in the $\text{pH}$ range equal to $\text{p}{K}_{\text{a}}-1$ to $\text{p}{K}_{\text{a}}+1$.

Answer to Problem 8.54AP

The value of partition coefficient for both the drugs will decrease on using water of $\text{pH }7.4$.

Explanation of Solution

The $\text{p}{K}_{\text{a}}$ value of the conjugated acids of both drugs is same and is equal to $9.5$. Therefore, both the drugs will be found in their conjugate acids forms at $\text{pH }7.4$ because the solution is sufficiently acidic for the protonation of the amino group of the drugs.

This means the polarity of both the drugs will increase due to which their solubility in the water phase will increase. Therefore, the value of partition coefficient for both the drugs will decrease.

Conclusion

The value of partition coefficient for both the drugs will decrease because both the drugs will be present in the conjugated acids form and therefore their solubility in the water will increase.

Interpretation Introduction

(f)

Interpretation:

The reason as to why the drugs are formulated in the form of hydrogen chloride instead of using their basic form is to be stated.

Concept introduction:

$\text{p}{K}_{\text{a}}$ of the acid represents the $\text{pH}$ at which the acid will be found in the protonated form or dissociated form. The acid is found in the dissociated form in the $\text{pH}$ range equal to $\text{p}{K}_{\text{a}}-1$ to $\text{p}{K}_{\text{a}}+1$.

Answer to Problem 8.54AP

The drugs are generally weak acids and bases and for dissolution or absorption in the body these forms are generally not ideal.

To boost their absorption and dissolution in the body, the drugs are formulated in the form of salts.

Explanation of Solution

The drugs are usually weak acids and bases but these forms are usually not optimal for the dissolution or absorption in the body. Medicines need to be water soluble as well.

The drugs are formulated in the form of the salts in order to increase their absorption and dissolution in the body. The salt forms are more optimal for the dissolution and boost its absorption in the stream of blood.

Conclusion

The drugs used in the form of salts in order to enhance its activity and dissolution in the body.