Exam 2 Flashcards
Solubility and Ionic Equilibria
T or F: Only drugs that are dissolved in their free molecule form in the body will be readily absorbed.
True. Drugs in their full particle form will not be readily absorbed
What is a nonelectrolyte?
Drug that is fully unionized/ uncharged. Examples include mannitol, glucose, and more.
T or F: A non-electrolyte solution with water will conduct electricity better than water alone.
False. They will both conduct electricity equally. Neither is better.
A high partition coefficient means the drug is more _________.
Lipophilic
A low partition coefficient means that drug is more __________
Hydrophilic (polar)
T or F: For all different types of soluble drugs, the ratio of oil and water solubility is approximately equal to the oil/water partition coeffincent.
False. This is only true if the solubility is not very high for the drug.
What two factor govern passive diffusion of drugs across biological membranes?
Oil solubility (Soil)
Molecular size/weight
T or F: The solubility of a drug in oil can be found by taking the rearranging the partition coefficient equation.
True. Soil can be found by multiplying Ko/w and Sw
T or F: Oil solubility can be estimated for high lipophilic drugs forming ideal or nearly deal solutions in an oil environment.
False. It can be estimated for moderately lipophilic drugs.
What are the 3 properties associated with ideal solutions?
- Volume of solution is equal to the sum of the individual components
- No heat is released is absorbed when components are mixed
- Components mix randomly in solution
T or F: If a drug is liquid at room temperature it has a high solubility.
False. If liquid at room temperature, the solubility is miscible as it is so high.
What is this equation used for?
This equation is used to determine the solubility of a solid drug at room temperature in oil using its mole fraction.
If the melting point is below 25C for this equation, then the solubility of the a solid drug in oil at room temperature is __________.
Miscible
For every ______C increase in melting point above room temperature, the mole fraction solubility in oil of an ideal solute falls by a factor of _______.
100C
10
T or F: Drugs with very high melting points that are placed in oil will have decrease solubility.
True!
Which one has miscible solubility in oil?
Benzene ring as it is a liquid at 25C because its melting point is 5.5C. Drugs that are liquid at room temperature have miscible solubility in oil. X2b=1
Which one is not miscible in oil at room temperature?
Naphthalene as it is a solid at room temperature meaning it will be soluble in oil.
T or F: For every 100C increase in MP above room temperature, solubility of a drug in oil and in water fall by a factor of 10.
True! This is true in both oil and water solubilty.
For every increase in logKo/w of ________ unit, water solubility of a drug falls by a factor of ________.
1 unit
10
What is the general solubility equation used to determine the solubility of a drug in water at room temperature?
Indomethacin is an NSAID with a MW of 385, mp if 159C, and a LogKo/w of 4.27. Estimate its water solubility in g? at 25C.
What is the effect of melting point of a drug on it solubility?
A. At mp >25C, higher mp leads to higher solubility
B. At mp >25C, higher mp leads to lower solubility
C. At all mps, higher mp leads to higher solubility
D. At all mps, higher mp leads to lower solubility
B. At mp >25C, higher mp leads to lower solubility
What is the effect of drug lipophilicity on its aqueous solubility?
A. Higher octanol/water partition coefficient leads to higher aqueous solubility
B. High octanol/water partition coefficient leads to lower aqueous solubility
C. Octanol/water partition coefficient is unrelated to lipophilicity
D. Lipophilicity has no effect on aqueous solubility.
B. High octanol/water partition coefficient leads to lower aqueous solubility
Which of these compounds would be expected to have a higher solubility in lipid membrane/oil?
They hame similar solubilities in oil. This is known through using the solubility in oil equation which only takes melting point into account. As the melting points are so similar, they have similar solubilities.
Which of these compounds would be expected to have a higher solubility in water?
Hydrocortisone as it has a lower logKo/w compared to estradiol.
Remember that every 1 unit increase in logKo/w decreases water solubility by a factor of 10.
What is a cosolevent?
This is a solvent added to the primary solvent at a smaller quantity than the primary solvent to increase the solubility of a compound in the primary solvent.
What are 3 common cosolvents used in pharmacy practice?
Ethanol, glycerin, and propylene glycol
Why are ethanol, glycerin, and propylene glycol often used a cosolvennts?
They are polar but much less polar than water and can substantially increase the solubility of organic compounds.
T or F: In most cases, we want drugs that are less polar than either solvents.
True. Normally we want non-polar drugs so they are less polar than the solvents. When this is the case, the solubility graph with a cosolvents looks like the image.
What does it mean for a drug to be non-polar?
It means it is less polar than the solvents it is in.
For non polar solutes, the solubility ____________ strongly with __________ fraction of cosolvent.
Increases
Increasing
T or F: Polar and semi-polar drugs behave the same way as non polar drugs in the sense that increasing the fraction of cosolvents increases the solubility.
False. Only non-polar molecules have that relationship with cosolvents.
What is the approximate effect of melting point of a drug on its solubility?
A. 10x decrease per 100C increase
B. 4x decrease per 100C increase
C. 10x decrease per 10C increase
D. 4x decrease per 10C increase
A. 10X decrease per 100C increase
Which of the following factors affect the solubility of a moderately lipophilic drug in oil (assuming that the liquid drug is miscible with oil)?
A. Melting point
B. Low Ko/w
C. Both
A. Melting point
What is the approximate effect of logKo/w of a drug on its aqueous solubility?
A. 10x decrease per 1 unit of logKo/w increase
B. 10x increase per 1 unit of logKo/w increase
C. 10x decrease per 10x logKo/w increase
D. 10x increase per 10x logKo/w increase
A. 10x decrease in solubility per 1 unit LogKo/w increase
What is Kw?
Ionization of water with the value of 1x10^-14 at room temperature. It does change at different temperatures.
What is the relationship between drug solubility and volume fraction of cosolvent for a drug that is less polar than the cosolvent in water?
A. Linear relationship of increasing solubility with increasing volume fraction of cosolvent
B. Linear relationship of decreasing solubility with increase volume fraction of cosolvent
C. Log-linear relationship of increasing solubility with increasing volume fraction of cosolvent
D. Log-linear relationship of decreasing solubility with increasing volume fraction of cosolvent
C. Log-linear relationship of increasing solubility with increasing volume fraction of cosolvent
At room temperature, the equilibrium constant for water, Kw, is what?
1 x 10^-14, giving it pKw to be 14
If a molecule with its pKa is given and added to water, will you be able to tell if the water becomes more acidic or basic?
No. You need to know if the drug is in its acid form or conjugate base/salt form.
The higher the ionic strength means the more __________ that is shield the effects of charges.
Ions
_______ __________ is important to colloid stability
Ionic strength
In order to calculate an accurate pH value, one must use both _________ and ________ coefficent.
Concentration
Activity coefficient
If you put valproic acid (pKa=4.8) in water, what happens to the pH of the water?
It decreases
If you put divalproex sodium into water (salt form of valproic acid), what happens to the pH of the water?
It increases because the salt form is also the conjugate base form.
Is morphine a weak acid or base?
Weak base. The morphine hydrochloride is the conjugate acid form which correlates to pKa being 7.87.
Is atropine a weak acid or base?
Atropine is a weak base. It conjugate acid/salt form is atropine sulfate which has the pKa of 9.65.
If more ions (higher ionic strength) are present, the interactions with the drug to the counter ion will be _______ strong.
Less
If there are less ions (lower ionic strength), the interactions with the drug to the counter ion will be _______ strong.
More
T or F: Ionic strength increases with the concentration of the ions.
True
T or F: Ionic strength increases with the number of charges on the ions.
True
What is the key formulation variable affecting the stability of gels, emulsions, and suspensions?
Ionic strength
Emulsions and suspensions are often stabilized by _________ _________.
Electrostatic Repulsion
If you decrease ionic strength, the stability of the compound will ___________.
Increase
If you increase ionic strength, the stability of the compound will __________.
Decrease
What two things affect gel making?
Ionic strength and pH
T or F: If you have a high ionic strength in the gel, then it will be less stable.
True. This means the repulsions are less and the gel is less stable.
Which of the following solutions would have the highest ionic strength? Consider both protons on H2SO4 to be strong acids.
A. 0.1M K2SO4
B. 0.1M KHSO4
C. 0.1M H2SO4 (equivalent to 0.2M Na H2SO4)
D. 0.1M Na2SO4
E. All solutions have similar ionic strength
E. All solutions have similar ionic strength
(all have same number of anions and cations as well as molar concentration which is what goes into ionic strength)
Phosphoric acid is a weak acid with pKa values of 2.12, 7.21, and 12.67. Given this information, which of the following solutions would have the highest ionic strength?
A. 0.1M K3PO4
B. 0.1M K2HPO4
C. 0.1M KH2PO4
D. 0.1M H3PO4
E. All solutions have equal ionic strength
A. 0.1M K3PO4 (dissociates into 3 K+ and 1 PO4^-3)
