Exam 1 Solutions

Question 1

What are the three different types of liquid dosage forms?

Answer 1

1. solutions
2. emulsions
3. suspensions

Question 2

What is a solution?

Answer 2

a homogenous molecular dispersion → like water but has the drug dissolved in it

Question 3

What is an emulsion?

Answer 3

not homogenous → is heterogenous in which liquid is suspended → can be oil in water or water in oil

Question 4

What is a suspension?

Answer 4

solid particles are suspended in liquid → examples are calamine lotion and pepto bismol

Question 5

What are some examples of solution dosage forms?

Answer 5

injectables, nasal solutions, ophthalmic solutions, otic solutions, irrigation solutions, enemas, douches, gargles, mouthwashes, juices

Question 6

What are some advantages of solution dosage forms?

Answer 6

1. homogenous → there are no problems of content uniformity (since it is essentially one phase because the drug has dissolved and is in solution)
2. easy to manufacture
3. good bioavailability → the drug is ready to be absorbed since the drug is already dissolved in the molecular level

Question 7

What are some disadvantages to solution dosage forms?

Answer 7

1. greater chance for the drug to be exposed to adverse reactions
2. not all drugs are suitable for solutions (like water soluble drugs)

Question 8

When can oil be used as a dosage form?

Answer 8

can be used for solutions but not for straight IV injections → IM injections are good but oil straight into the bloodstream is bad

Question 9

What are the components of solution dosage forms?

Answer 9

1. active ingredient (aka the drug)
2. solvent
3. buffering agent
4. preservative
5. antioxidant, chelating agent
6. flavor and sweetener

Question 10

What are some examples of solvents to be used in a solution dosage form?

Answer 10

water and vegetable oils (for long acting parenterals)

Question 11

What is a co-solvent?

Answer 11

helps the drug dissolve in addition to the solvent → examples include ethanol, glycerin, propylene glycol

Question 12

What is the role of a preservative in a solution dosage form?

Answer 12

is used for stability issues → usually antimicrobial agents

Question 13

What is the role of an antioxidant/chelating agent in a solution dosage form?

Answer 13

reduces chemical agents

Question 14

What is the role of a flavor/sweetener in a solution dosage form?

Answer 14

used for oral solution products → examples include sorbitol and sucrose

Question 15

What is the principle behind a buffer?

Answer 15

1. keeps the pH constant
2. is a solution of a weak acid and a salt of its conjugate base
3. weak acid can remove added base (OH-)
4. salt (aka conjugate base) can remove added acid (H+)

Question 16

What is the Henderson-Hasselbach equation used for?

Answer 16

to calculate how much acid and salt we have (pH = pKa + log ([A-]/[HA]))

Question 17

What is the buffering capacity?

Answer 17

the ability of a buffer to resist a change in pH due to added OH- or H+ → the Van Slyke equation which is β = 2.3C*(Ka[H3O+]/(Ka+[H3O+])^2) where C is the total buffer concentration = [Ha] + [A-] → the max is when pH = pKa

Question 18

When is buffering capacity (β) the greatest (aka at maximum)?

Answer 18

when pH = pKa of the buffer

Question 19

What are some common pharmaceutical buffers?

Answer 19

acetic acid, citric acid (has 3 ionization constants), glycine (has 2 ionization constants), phosphoric acid (has 3 ionization constants)

Question 20

How do you choose a buffer (aka acid and the conjugate base) when given the pH?

Answer 20

choose the pair (acid and conjugate base) with a pKa closest to the pH value for the highest buffering capacity

Question 21

What is the difference between monobasic, dibasic, and tribasic?

Answer 21

monobasic = one negative charge
dibasic = two negative charges
tribasic = three negative charges

Question 22

When given a graph of log k vs pH, how do you know what pH is where the drug is most stable?

Answer 22

the dip in the graph (aka the lowest point) is where the drug will be kept and not be degraded the fastest so it’s the pH where the drug would be most stable (since higher k value = higher degradation)

Question 23

What are things to keep in mind with the selection of the pH?

Answer 23

1. use pH that provides the maximum stability for the drug
2. want to minimize irritation with parenteral, ophthalmic, or nasal dosage forms by adjusting pH to be the same as the pH of the body fluid (like blood, interstitial fluid, or tears at pH of 7.4) → want to match pH of body fluid is possible, but if not, can minimize buffering capacity, minimize volume, and administer slowly

Question 24

Why is it important to match the pH with the pH of body fluid when possible?

Answer 24

it is painful for the patient is the pH is quite different than physiological pH → want more on the lower side than higher side since higher pH can cause more pain

Question 25

Why is it important to match the pH with the pH of body fluid when possible?

Answer 25

it is painful for the patient is the pH is quite different than physiological pH → want more on the lower side than higher side since higher pH can cause more pain

Question 26

What is the purpose of antimicrobial preservatives?

Answer 26

1. protect the patient from pathogens | 2. maintain the potency and stability of the dosage form

Question 27

What is the mechanism of action behind antimicrobial preservatives?

Answer 27

1. they can absorb the bacterial membrane and disrupt it → the membrane is lipophilic and has a net negative surface charge 2. absorption is due to lipid solubility → alcohols, acids, esters 3. absorption is due to electrostatic attraction → quaternary ammonium compounds which are cationic and can interact with the negative surface charge of the membrane

Question 28

What is the bacterial content allowed in ampules?

Answer 28

has to be sterile, single dose, and no preservative is needed

Question 29

What is the bacterial content allowed in multiple dose vials?

Answer 29

has to be sterile, may contain up to 10 doses, need a preservative to kill microorganisms introduced during use

Question 30

What is the bacterial content allowed in ophthalmic solutions?

Answer 30

has to be sterile, must contain a preservative if it's packaged in a multiple dose container

Question 31

What is the bacterial content allowed in oral liquids?

Answer 31

doesn't need to be sterile but shouldn't contain pathogens (the immune system can manage organisms) → FDA has limited the number of organisms (such as E. coli) to be less than 100 per mL → preservative is needed if packaged in multiple dose packages

Question 32

What is the bacterial content allowed in oral solids?

Answer 32

is less likely to carry bacteria than liquid forms so it does not need to be sterile (pathogens don't like solids since there is no water) → pathogen contamination is still a concern (like Salmonella) so raw materials are tested and the manufacturing facility should be clean

Question 33

What are the characteristics of an ideal preservative?

Answer 33

1. effective in low concentrations against a wide variety of organisms 2. soluble in formulation → to be available 3. non-toxic → should only be toxic to bacteria 4. stable → to keep the drug active

Question 34

What is the main mechanism behind a pharmaceutical preservative?

Answer 34

to affect the bacterial membrane of the pathogen but to leave the patient's cell membranes intact and unharmed

Question 35

What are the classes of pharmaceutical preservatives?

Answer 35

1. alcohols 2. acids 3. esters of p-hydroxybenzoic acid (parabens) 4. quaternary ammonium compounds

Question 36

What are some examples of alcohol preservatives?

Answer 36

1. ethanol → required to be greater than 15%, limited to oral products, can be lost due to volatility (since concentration can drop as it evaporates once it's opened and closed over time) 2. benzyl alcohol → has local anesthetic action, burning taste so not used orally, is water soluble and is stable over a wide pH range so it is widely used in parenterals 3. chlorobutanol → campor like odor and taste so not used orally, used in parenterals and ophthalmics, is volatile (like ethanol) in which its concentration can drop as it is lost through rubber stoppers and plastic containers

Question 37

What is important about acid pharmaceutical preservatives?

Answer 37

1. is only active in unionized (lipid soluble) form since if it is ionized/charged, it won't work 2. needs to be fully protonated → the pH needs to be below the pKa value

Question 38

What are some examples of acid pharmaceutical preservatives?

Answer 38

1. benzoic acid (pKa is 4.2) → used in oral products (active in pH below 4.2) 2. sorbic acid (pKa is 4.8) → used in oral products, is excellent for molds and yeasts (effective at pH below 4.8)

Question 39

What's important to know about esters of p-hydroxybenzoic acid (parabens) as pharmaceutical preservatives?

Answer 39

1. widely used orally → not ionized but hydrolyzed rapidly at pH values above 7 (aka loses its activity at pH above 7), anesthetizes the tongue 2. low solubility is a problem 3. can cause skin sensitization when used in dermatological products

Question 40

What are some examples of parabens as pharmaceutical preservatives?

Answer 40

the most lipophilic ones (propyl paraben and butyl paraben) are best against mold and yeast while the least lipophilic ones (methyl paraben and ethyl paraben) are best against bacteria

Question 41

What is important to know about quaternary ammonium compounds?

Answer 41

1. widely used in ophthalmics and is very water soluble and fast killing 2. there may be some incompatibility issues due to positive charge → is okay to use in small amounts like eyedrops but no systemic use (aka no injectables) because of the charge that can damage proteins and membranes

Question 42

What are some examples of quaternary ammonium compounds as pharmaceutical preservatives?

Answer 42

1. benzalkonium chloride (Zephirin) | 2. cetyltrimethylammonium chloride (Cepryn)

Question 43

What are the factors that affect preservative action?

Answer 43

1. pH → only the unionized (aka fully protonated when pH is below pKa) species of weak acids are effective → have to add more total weak acid when pH is above pKa in order to have effective concentration of unionized species 2. complex formation → only the uncomplexed (free) preservative is active 3. absorption by solids → only the unabsorbed preservative is active 4. chemical stability → consider the shelf life

Question 44

What are antioxidants?

Answer 44

they are used as protectants of liquid products

Question 45

Why are antioxidants used?

Answer 45

drug substances are less stable in aqueous media than solid dosage forms → acid base reactions, acid/base catalysis, oxidation, or reduction may occur from ingredient-ingredient interactions or container-product interactions

Question 46

What is the main degradation pathway of pharmaceuticals?

Answer 46

oxidation! (examples include vitamins, essential oils, fats, and oils)

Question 47

What are the two types of oxidation?

Answer 47

1. auto-oxidation → an automatic reaction with oxygen without drastic external interference in which the molecule is turned to something else 2. can be initiated/accelerated by heat, light, peroxides, metals (copper, iron) to make free radicals that react with oxygen to create more free radicals

Question 48

What are the three types of antioxidants?

Answer 48

1. free radical scavengers 2. reducing agents 3. chelating agents

Question 49

What are free radical scavengers?

Answer 49

they retard/delay oxidation by rapidly reacting with free radicals (aka removes them) → examples include 1. propyl, octyl, dodecyl esters of gallic acid 2. butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) 3. tocopherols, Vitamin E

Question 50

What are reducing agents?

Answer 50

react with oxygen before the active compound can (consumes oxygen) → has lower redox potentials than the drug so it's more readily oxidized → examples: 1. sodium bisulfite 2. ascorbic acid 3. thiols

Question 51

What are chelating agents?

Answer 51

they don't do anything regarding free radicals or oxygen, but they get rid of metals → considered antioxidant synergists and have little antioxidant effect themselves but removes trace metals → examples: 1. citric acid 2. EDTA (ethylenediaminetetraacetic acid)