Physical Pharmacy Exam 2

If solubility for a drug is poor, its oral absorption is likely to be: (choose from: poor, good, excellent, can't say)

Poor

What is the main difference between rock salt and table salt

Rate of Solubility

Which of the following solutions are encountered in Pharmacy?

- solid/solid

-liquid/liquid

-solid/liquid

USP defines soluble as one part of solute in 10 to 30 parts of the solvent. Here the word "part" refers to

Mass: Grams

Liquid: mL

Regarding the Noyes Whitney equation [dC/dt=DA/h* (Cs-C)], when you add a spoon full of sugar into your morning coffee and stir, this is the parameter that you are most directly altering

Stagnant layer thickness

In pharmaceutical manufacturing, non-polar solvents like acetone are not used to formulate drugs

True

For weakly acidic drug, as the pH of the medium increases, its distribution coefficient (LogD)

Becomes lower than than its logP

Which of the following represents an ascending order (low to high) of water solubility

Calcium sulfate, barium chloride, potassium iodide

The solubility of calcium chloride in water increased with temperature. This means:

endothermic reaction

Regarding pKa of a drug, choose the correct statement/s from below

- pH at which is 50% ionized

- pH at which is 50% unionized

-pKa is a chemical property of a drug

Atropine has a solubility of 1 part in 455 parts of water. Atropine sulfate as a solubility of 1 part in 0.5 of water. The best explanation for this is:

atropine sulfate ionizes in water

Codeine is a weakly basic drug. This means that it is least ionized in acidic pH

false

The partition coefficient of a drug (LogP) is found to be 3. This means

it is a 1000 times more soluble in water than in oil

Choose the solvents from below that are especially useful in solubilizing unionized drugs, when used in combination with water (you are allowed to select more than one )

propylene glycol and ethanol

In general, divalent salts (e.g. Calcium sulfate are more soluble in water than monovalent salts (e.g. potassium iodide)

false

As temperature of a liquid increases, the dissolved gas in it tends to reduce. This phenomenon can be opposed by the following

increased pressure

A brand of Lugol's solution has 10 parts of potassium iodide, 5 parts of iodine and 85 part of water. Note that both KI and I2 at room temperature are crystalline solids. According to USP this may be expressed as:

10% W/V KI, 5% W/V I2 in water

Regarding benzene and phenol, which of the following statements are true?

-Benzene is more non-polar

-Phenol is more polar

-Benzene is less soluble in water

-Phenol is more soluble in water

Dipole-Dipole interactions are shown by which of the following examples

sugar in water

For some protein formulations, adding modest amount of salt will prevent protein aggregation

True

Saturated solutions of two different drugs in water will have comparable concentrations of the respective drug

false

The immiscible liquids used typically to test partition coefficients of drugs are:

n-octanol and water

Salicylic acid is a weakly acidic drug. This means it is most ionized in basic pH

true

Ion-dipole bonds are involved in which of the following solutions?

normal saline, Lugol's solution

FDA does not allow the use of alcohol as a co-solvent in formulations meant for children below 6 years of age.

false

Which of the following indicates the substance A will spread over substance B where Gamma indicates surface tension

γA+ γB - γAB - 2γA = +ve

During surface tension determination, it was found that the force require to move the movable bar EK to a new position E'K' is 436 dynes, and the length of the bar is 6 cm. Calculate the surface tension of the solution.

36.33 dynes/cm

Select ALL statements that are true: For a drug delivered as a oral table, which of the following statements apply?

1. Drug particles need to dissolve into individual molecules

2. The tablet needs to first disintegrate into smaller pieces in the GI tract

Which of the following statements is true in terms of reducing unintended adsorption of a protein drug to the container.

Low dose of albumin is induced in the formulation

In a beaker full of water, the water molecules in the bulk phase experience the following kind of forces:

cohesive forces only

Which of the following pairs does not show significant interfacial/surface tension at equilibrium

water and propylene glycol

Adsorption is generally an endothermic process. Therefore, as temperature increases, adsorption also increases.

false

Which of the following suggests a high chance of wetting of a given particle by water

low contact angle between water and the particle

Which of the following conditions will enable the spreading of the material Z over material M

adhesion forces between Z and M are greater than cohesion forces within Z

Amphoteric surfactants may have both positive and negative charge on the same molecule, depending on the medium's pH

True

Simethicone, a silicone oil, is given to babies as drops to relieve gas. With reference to its use, which of the following statements is true.

antifoaming agent with low HLB value

In general, the greater the logP for a drug, the better is its oral absorption

false

According to Noyce Whitney equation, the rate of dissolution of a drug particle is inversely proportional to the following parameter:

stagnant layer thickness

The units of surface tension in cgs the system are dynes/cm squared

false

For an adsorbing surface, as pressure increases, its capacity to adsorb also increases, at least initially

True

Cationic surfactants can produce a lot of foam and considered irritating to skin

false

In terms of combining two different types of surfactants, which of the following is not acceptable

Anionic and Cationic Surfactants

For a weak acid like the nosteroidal anti-inflammatory drug, indomethacin (pKa= 4.5), which of the following statements is likely true?

at pH 10, Log D is lower than log P

Anionic Surfactants can bind to negatively charged proteins and therefore used in hair conditioners

false

Owing to their non-irritating nature, the following type of surfactants are used in baby shampoos

nonionic

Since hexane spreads on water, water must naturally spread on hexane

false

Force is defined as mass* acceleration due to gravity or F=ma

True

Which of the following statements is INCORRECT

Bile salts help in emulsifying water soluble vitamins

With reference to water, the interfacial tension of some liquids are shown below. Choose the liquid that is likely to spread on water the easiest.

1-Octanol; 8.51

The key difference between table salt and rock salt is

1. rate of solubility

2. Particle size

With regard to surface active agents, which of the following is a true statement

They are amphiphilic

At a given temperature, which of the following fluids has the highest viscosity?

Whole milk

In atherosclerosis, the arteriole diameter narrows due to deposition of plaques. Based on Poiseuille's equation, this can lead to:

an increase in the work done by the heart

For extra protection, flak jackets maybe infused with a shear thinning fluid

false

Based on Poiseuille's law, a doubling of the radius of an artery will lead to which of the following

A 16 fold increase in the blood flow

In anemic patients, since the number of RBCs may be lower, their blood may have higher visocity

False

A graph that plots the relationship between shear stress and rate of shear

Rheogram

Regarding mucin secretion, which of the following statements is FALSE?

In its natural form it exhibits newtonian flow

Polymes like methyl cellulose will form a gel like consistency when used as a suspending medium. Upon shaking, they become more fluid

Molecules transform from globular to linear form

When shear stress is plotted on x-axis and rate of shear is plotted on the y-axis, the slope of the graph of the graph is equal to viscosity

False

Rouleaux formation or stacking of the RBCs in an arteriole may lead to viscoelastic property of the blood

False

Penicillin G Procaine injection is formulated to exhibit pseudoplastic flow, identify the TRUE statement from below

This helps in the easy flow during injection

Some fluids show zero rate of shear at low values of shear stress. Such fluids are describe to exhibit the following

Plastic

With shear stress plotted on x-axis and rate of shear plotted on the y-axis, a rheogram shows a straight line intersecting the origin. This kind of fluid behavior is best described as

Newtonian System

Einstein's Equation explains

as colloidal particles increase, viscosity increases

Based on Poseuille's law that relates blood flow to various physical factors, choose the most appropriate statement:

- Higher the pressure gradient, higher the flow rate

-Lower the arterial diameter, smaller the flow

- Higher blood viscosity, lower flow

In the condition of polycythemia vera, total blood cell count increases substantially leading to shear thickening behavior of blood

true

Liquid and solid materials offer resistance to flow. The measure of this resistance is called

Viscosity

The unit of viscosity in cgs is:

poise

synovial fluid becomes more viscous in ageing patients leading to joint inflammation

false

with regret to it normal rheological behavior in the body, the blood in small arteries may not show a linear relationship between applied stress and rate of shear

true

an antacid suspension was being mixed in a ribbon mixer. Since the operator thought that it was taking too long, the rotor speed increased. However, instead of speeding up, the rotor slowly ground to a halt. Which of the following statements may help explain this phenomenon

There is more solid and less liquid in the formulation

Which of the following is NOT an example of high viscosity material?

Whey

In a netwonian system of flow, shear stress is proportional to:

rate of shear

Shear stress is defined as:

force/area in the equation

F/a=n*dV/dR

When shear stress is plotted on the x-axis and rate of shear on y-axis, the slope of the line is equal to

fluidity or phi

Using the rheogram for a newtonian fluid, it was found that for a 40 unit change in shear stress plotted on the x-axis, there was 200 unit change on the y-axis (rate of shear). Based on this info, which is true:

The viscosity of the system is 0.2 poise

slope=rise/run

slope= 200/40 = 5

this is fluidity (units 1/poise)

Viscosity is 1/slope or 1/fluidity = 1/5= 0.2 poise or 20 centipoise

For a newtonian system, a large change in shear stress is caused by a small change in the rate of shear. Based on this, how would you categorize this system?

High viscosity since a large change in shear stress is only causing a small change in flow

As temperature increases, the fluid might change as follows:

decreased viscosity; temp is inversely proportional to viscosity so a and b are the same

For gases, a temp increases, viscosity reduces

False; as temp increases, gas viscosity tends to increase due to random motion

At high pressures, engine oil viscosity increases

true

The proof for Einstein's equation regarding viscosity and suspended particles can be seen from the follow grocery item:

Whole milk has higher viscosity out of all choices. It has more suspended particles supporting Einstein's observation. Water has no suspended particles and has the leases viscosity from the list followed by whey

Which of the following systems has a yield point

Plastic

Materials that show a yield point are

Bingham Bodies

On a graph, if the line going up follows a different path than the line coming down, its supposed to exhibit

Hysteresis, thixotropy, or sol-gel transformation

A shear thickening flow is likely to be exhibited by the following material:

A suspension with high fraction of particles; dilatant flow is exhibited by formulations with a high degree of suspended particles (>60%)

A systemic dose of epinephrine (adrenaline) reduced the radius of a blood vessel from 4 mm to 2 mm. All other factors remaining the same, the flow rate in the artery

reduces by 16x

Flow rate is proportional to the radius of the blood vessel, raised to its 4th power. If the radius is halved, the flow rate will decrease by 2 raised to 4=16 times

In polycythemia vera, as the suspended cells greatly increase in number, the viscosity of blood also increases.

True

In your own words, how would you explain the difference between solubility and dissolution of a drug

Solubility is a physical constant. In a given liquid, at a given temperature, the equilibrium solubility of a drug is a constant and is an equilibrium property of the drug.

Dissolution indicates how quickly the drug reaches maximum equilibrium solubility. Thus, dissolution is a rate process and indicates the speed of solubility

For a solution of CO2 in water, an increase in temperature would improve CO2 solubility

False; increase in temperature increases the kinetic energy of the gas molecule and helps them escape the solution. So partial pressure of the dissolved CO2 decreases

For saturated solutions of aspirin and acetaminophen, you expect comparable (or same) molar concentrations of the drug

Fales; because they are both saturated. There is no expectation that their concentrations should be the same. Aspirin solubility is around 3 mg/ml at RT while acetaminophen is approx 17 mg/mL. Their MW is 180 and 154 respectively. Thus, aspirin 3 mg/mL= 0.0016 M. For acetaminophen (17 mg/mL) is 0.11 M

To improve dissolution of crystal sugar in water, you may heat it. This suggests that:

Endothermic reaction; external heat improves dissolution. The heat of the solution would be negative for such reaction

According to Noyce Whitney equation, to improve dissolution, you might do the following change to your tablet formulation

Reduce the drug's average particle size

Which of the following is true regarding organic solvents?

They can extract active principles; they are extract fat soluble/non-polar active principles from plants. DO NOT HAVE high dielectric or facilitate ionic interactions or have dipole moment/polarity

USP defines very soluble drug as: 1 part of drug soluble in part of the liquid like water. One part here means

gram/mL

mass of drug and liquid

In order for a drug to be absorbed orally, it needs to be soluble within the GI lumen

True. Without some degree of aqueous (water) solubility, drugs are unlikely to be orally absorbed

The pKa of codeine, a weak base, is 8.2. This means:

At a pH of 7.2, codeine is mostly ionized;

Remember weak bases ionize at acidic pH (lower pKa). Since pKa is 8.2, at that pH, codeine is 50:50 ionized/unionized. At higher than 8.2 pH (e.g. 9.2), it would be mostly unionized. 7.2 ionized

For a drug to be orally absorbed, which of the following properties is highly desirable?

Some water solubility and some lipid solubility; extremely high lipid solubility is not good as the drug may remain in the body in fat depots (adipose tissue) for an unnecessarily long time. Reasonable amount of lipid and water solubility is desirable for most drugs.

Why is n-octanol and not some other lipohillic solvent used for determining the partition coefficient of drugs (LogP)

because like cellular bilayer lipids, it has polarity (due to OH groups) and a lot of lipophilicity (. due to the long 8 carbon chain)

According to Noyes-Whitney equation, as the viscosity of the dissolution medium increases, the rate of dissolution decreases

True, since eta(n) is the denominator, there is inverse relationship between dissolution rate and viscosity