ceutics exam 3

what is the definition of biopharmaceutics

how the physical/chemicalproperties of a drug and its dosage forms affect onset, duration, and intensity of action

what is the definition of pharmacokinetics

the time course of drug absorption, distribution, metabolism, and elimination. what the body does to the drug

what is the definition of pharmacodynamics

the relationship between drug concentration at the site of action and the resulting effect. what the drug does to the body.

what are the advantages of formulating drugs in dosage forms

dosing accuracy, administration and handling, stability, site degradation, local irritation, organoleptic masking, and pk modification.

define dosing accuracy

is the dose too small to handle or measure precisely

define administration and handling

raw powders/chemicals are impractical to give.

define stability

protect from light, moisture, and heat.

define site degradation

shield drugs from harsh environments

define local irritation

prevent tissue injury from high local concentration

define organoleptic masking

hide unpleasant taste or smell

define pk modification

control the rate/pattern of drug release.

what is the definition of bioavailability

the fraction of an administered dose of unchanged drug that reached the systematic circulation.

what factors can affect bioavailability

route of administration and dosage form

what is the x axis on a blood drug concentration curve

time

what is the y axis on a blood drug concentration curve

drug concentration

what is the lower line on a blood drug concentration curve

MEC- maximum effective concentration

what is the upper line on a blood drug concentration curve

MSC- maximum safe concentration

what is the space between the curves on a blood drug concentration curve

therapeutic window

what is the onset of action on a blood drug concentration curve

time after taking dose to when drug concentration reaches the minimum effective concentration

what is the duration of action on a blood drug concentration curve

time that the drug concentration stays above the minimum effective concentration line

what are these examples of: IV, IM, sublingual, oral, transdermal, topical.

routes of drug administration

what effects does dosage form have on drug absorption

faster absorption leads to a quicker onset of action.

what is the definition of polymorphism

the same drug molecule can exist in more than one crystalline arrangement

when it comes to polymorphs, what’s the correlation between melting point and solubility

higher melting point, lower solubility

what is the definition of crystalline, its solubility, and stability

arranged in a fixed fashion. less soluble, more stable.

what is the definition of amorphous, its solubility, and stability

random arrangement. more soluble, less stable.

what is notable about fast acting drugs

they contain a more soluble ester

what is notable about long acting drugs

they contain a less soluble ester

regarding weak electrolytes, describe the dissociation and solubility

dissociate partially, less soluble

for weak bases, when pH is 2 units _ pKa, 99% of the drug is unionized

above

for weak bases, when pH is 2 units _ pKa, 99% of the drug is ionized

below

what is the isoelectric point

pH at which the molecule exists in the form of a zwitterion

what is the definition of zwitterion form

the molecule possesses a positive and negative ion

for weak acids, when pH is 2 units _ pKa 99% of the drug is unionized

below

for weak acids, when pH is 2 units _ pKa, 99% of the drug is ionized

above

what step does the IV route bypass

absorption

what are van der waals forces

weak, short range attractions between molecules. they contribute to solubility and complexation.

which state of matter has the strongest inter molecular forces

solids

which state of matter has the weakest intermolecular forces

gases

what is the relationship between intermolecular forces and melting point

stronger forces mean a higher melting point

describe the melting point for crystalline solids

definite, and sharp

describe the relationship between melting point and solubility

higher melting point, lower solubility

describe the relationship between intermolecular forces and solubility

weak IMFs, higher solubility

rank these from highest to lowest solubility

1. amorphous acetaminophen

2. crystalline form with lower melting temperature

3. crystalline form with higher melting temperature

1, 2, 3

define an anhydrous form

no water is incorporated into the crystal lattice

define a hydrate form

water molecules are incorporated into the crystal lattice, further stabilizing it.

which form is more soluble: anhydrous or hydrate

anhydrous

what is the eutectic point

the lowest temperature at which a liquid phase can exist for a given mixture of 2 solids

which has a higher boiling point: cis or trans molecules

cis

A pharmaceutical scientist has worked on the development of a chloramphenicol palmitate product to improve the drug's bioavailability by using different polymorphic forms. Which pharmaceutical area is this scientist working in?

Biopharmaceutics

The structures and melting points of two beta agonists are shown below.Based on the melting points shown above, which drug would have higher solubility in water?

Metaproterenol

Docosanoic acid and the omega-3 fatty acid DHA are both C-22 carboxylic acids; DHA has six double bonds. One of the two compounds is an oily liquid at room temperature, and the other is a waxy solid. Based on this information, which compound is the waxy solid?

Ducosanoic acid

Two organic compounds have the same molecular weight, but compound A has a greater latent heat of fusion than compound B. Based on this information, which compound would likely have the higher melting point?

Compound A

A drug compound can exist in both amorphous and crystalline forms. If a formulation contains both forms, which form is more likely to cause a stability issue during storage?

Amorphous form

What is the area of study concerned with the physical and chemical properties of drugs and their proper dosage forms as related to the onset, duration, and intensity of drug action?

Biopharmaceutics

What is the portion of an administered dose of unchanged drug that reaches the systemic circulation, which is proportional to the “area under the curve (AUC)” of a plasma drug concentration versus time curve?

Bioavailability

What is the route of drug administration via the body site between the cheek and gums, used for local or systemic drug action?

Buccal

True or False: Subcutaneous administration of a drug tends to result in higher bioavailability compared to oral administration of the same drug at the same dose.

True

Using a spray-drying formulation approach, a pharmaceutical scientist converted a poorly soluble crystalline cephalosporin into its amorphous form for a tablet dosage form. What is the likely impact on oral bioavailability?

An increase in bioavailability

A drug compound with a lower melting point is likely to be __________ soluble than a drug compound with a higher melting point (all else being equal).

more

Which of the following theophylline compounds would have greater solubility in water?

Theophylline anhydrous

Which of the following acetaminophen products would be less soluble in water?

Crystalline acetaminophen

Considering the isomerism of a drug compound, which isomer of a solid drug compound would have a higher melting temperature?

Trans-isomer

For a liquid drug molecule that shows isomerism, which isomer of the drug molecule would have a higher boiling temperature?

Cis- form

Itraconazole (Sporanox capsules) is an oral medication for fungal infections. It is a weak base with a pKa of 3.7. Taking Sporanox with an antacid medication significantly affects its therapeutic activity. Considering the two rate processes associated with oral drug absorption, what would be the effect of the presence of an antacid (which removes acid from the stomach) on itraconazole dissolution in the stomach?

Decreases drug dissolution

Itraconazole (Sporanox capsules) is an oral medication for fungal infections. It is a weak base with a pKa of 3.7. Taking Sporanox with an antacid medication significantly affects its therapeutic activity. Considering the rise of stomach pH in the presence of an antacid, what would you expect to happen to the ratio of ionized to unionized itraconazole? Recall the pH partition theory.

More drug in undissociated state

Itraconazole (Sporanox capsules) is an oral medication for fungal infections. It is a weak base with a pKa of 3.7. Taking Sporanox with an antacid medication significantly affects its therapeutic activity.Considering the conflicted effect of the stomach pH change caused by the antacid on itraconazole absorption, what do you think is the apparent effect of an antacid on itraconazole absorption? (Hint: consider the sequence of drug absorption process.)

Lowers drug absorption

Itraconazole (Sporanox capsules) is an oral medication for fungal infections. It is a weak base with a pKa of 3.7. Taking Sporanox with an antacid medication significantly affects its therapeutic activity.Considering the effect of an antacid on itraconazole absorption, what would be your recommendation, as a pharmacist, to a patient who needs both itraconazole and an antacid?

Recommend the patient take the antacid at least 2 hours before or after taking Sporanox.    

Sulfadiazine is a weakly acidic drug that is eliminated primarily by renal excretion in the urine. Its solubility decreases in acidic urine, which can cause the drug to precipitate in the renal tubules and lead to acute crystal nephropathy. Which of the following is NOT an appropriate option for treating this complication?

Administering ammonium chloride to acidify the urine

The drug in _________ form is more permeable to the membrane for drug absorption. The _________ form of a drug is less water-soluble. 

Unionized; Unionized

A salt of a strong acid and a weak base ___________ the pH of the solution.

Decreases

For an organic weak acid drug, the percentage of unionized form of the drug is roughly 99% at a pH which is 2 units ________ the pK_a

Below

For an organic weak base drug, the percentage of ionized form of the drug would be 99% at a pH which is 2 units ________ the pK_a 

Below

What is the pH of a solution containing a hydroxide (OH^-) concentration of 1×10^-10 M? pOH=-log(OH), 14-x=answer

4

Itraconazole (Sporanox capsules) is a common oral medication that can be used to treat fungal infections. It is a weak base with a pK_a of 3.7. Which part of the gastrointestinal tract would render greater itraconazole absorption?

Distal small intestine (pH is around 7.4, neutral)

Intrinsic solubility (S_o) is the concentration of a(n)  ___________ weak electrolyte in a solution that is in equilibrium with the solid phase. The intrinsic solubility of the weak electrolyte ____________ as pH increases.

unionized; remains same

Total (apparent) solubility of a __________________ approaches the intrinsic solubility as the solution pH is lowered.

Weak acid

Sulfadiazine is a weak acid drug used to treat bacterial infections. Total solubility of sulfadiazine will ___________ as pH decreases.

Decreases

Maalox is an antiacid to relieve the symptoms of stomach upset and heartburn. Its main components are Al(OH)₃ and Mg(OH)_2, which are poorly soluble strong electrolytes. What would be the impact of Mg (Gylcinate), a highly soluble supplement, on the solubility of Mg(OH)₂ in Maalox?

Decrease solubility

Ferric hydroxide, Fe(OH)₃, is an iron supplement and a poorly soluble strong electrolyte. What is the impact of co-administrating calcium citrate, Ca₃(Citrate)₂, on the solubility of Fe(OH)₃? Citrate is known to tie up ferric iron (Fe³⁺).

Increase the solubility

If you need a buffer with a greater buffer capacity, which of following should you choose?

NaH₂PO₄ (0.3 M) +Na₂HPO₄ (0.3 M)

If you need to formulate an eye drop using an acetate buffer (pKa = 4.76) at pH 4.5, which of the following would be most preferable for not causing eye irritation?

Acetic acid (0.001 M) +sodium acetate (0.001 M)

If an eye drop was formulated using a buffer of pH 4.5, which of the following would be the preferred dose of the eye drop to minimize tissue irritation?

1 gtt

Which of following buffers has the greatest buffer capacity? The base has a pK_a of 8.5?

[base]=[salt] =0.2 M, pH=8.7

The buffer capacity of an acid buffer is “0.575×C” when pH equals to the pK_a, where C counts only [acid] concentration in the buffer.

False

A drug is to be compounded as an eye drop. Knowing that the drug is unstable at pH 7.4 but stable at pH 3.0, a buffer of pH 3.0 was selected to fill the order. For compounding the drug, which of following buffers should be used?

pH 3.0 buffer with a low buffer capacity

An acidic buffer prepared from a weak acid with a pK_a of 4.76 will be highly effective as a buffer, resistant to a pH change caused by the addition of a base, at pH 7.4.

False

Which of the following dosage forms would not be subject to dissolution-limited drug absorption?

Oral solutions

Which of the following drugs would dissolve the slowest?

Crystalline solid drugs

Two brands of the oral antidiabetic drug glyburide were compared for drug absorption. A 3 mg tablet of one brand produced slightly higher plasma levels, reached more quickly, than a 5 mg tablet of the other brand. The main difference between the two was that the 3 mg brand contained micronized glyburide. Which variable in the Noyes-Whitney equation was most affected by this difference?

Surface area, S

It is often recommended to take tablets and capsules with a large glass of water. Which of the following variable in the Noyes-Whitney equation would be most affected by the large volume of water?

Cb

Cyclosporine, an immunosuppressant, is a substrate of P-glycoprotein (P-gp), an ATP-dependent efflux pump expressed on the apical surface of intestinal epithelial cells (enterocytes). Grapefruit juice is an inhibitor of P-gp and first-pass metabolizing enzyme CYP3A4. Based on this, which of the following is the most likely effect on cyclosporine bioavailability when the drug is taken with grapefruit juice?

Cyclosporine bioavailability will increase.

Which of the following dosage forms does not require dissolution before the drug can be absorbed?

Solutions

A drug was formulated as a salt. Which of the following variables in the Noyes-Whitney equation would be most affected by this choice of salt form?

Cs

Food intake affects drug dissolution and absorption. It increases the viscosity of gastric fluid, resulting in a(n) ______________ in the drug's diffusion coefficient (D) and a(n) _________________ in drug absorption.

decrease; decrease

Based on the rate processes involved in oral drug absorption, which of the following best describes oral solutions?

absorption rate-limited drug absorption

Paracellular drug transport requires the drug to partition into cell membranes.

False

Two drugs have different partition coefficients. Drug A has a log P of 2.5, while drug B has a log P of −1.0. Which drug would be expected to show greater absorption?

Drug A

Carrier-mediated active drug transport requires energy.

True

Carrier-mediated facilitated drug transport can move drugs against a concentration gradient.

False