Block3 Lecture1

Question 1

What are the 3 classes of incompatibilities?

Answer 1

therapeutic, chemical, physical

Question 2

Define a therapeutic incompatibility.

Answer 2

drug combo with antagonistic or synergistic effects

Question 3

Define a chemical incompatibility.

Answer 3

covalent bond changes in drug or excipient upon reconstitution or mixing prior to administration

Question 4

Define a physical incompatibility.

Answer 4

changes in non-covalent interactions upon reconstitution or mixing prior to administration

Question 5

Define stability.

Answer 5

time during which the drug product retains integrity in terms of quality and chemical identity of API

Question 6

What are the sites for incompatibility in an administration set?

Answer 6

1) solution, 2) additive, 3) y-site, 4) syringe

Question 7

Define additive instability.

Answer 7

instability between drug and minibag solution

Question 8

define solution instability.

Answer 8

instability of drug with infusion solution

Question 9

define y-site instability.

Answer 9

instability between 2 drugs at site of mixing

Question 10

define syringe instability.

Answer 10

instability between 2+ drugs in same syringe

Question 11

What are common co-solvents?

Answer 11

ethanol, glycerin, propylene glycol, low-MW PEG

Question 12

define co-solvent

Answer 12

water-miscible organic solvents that are biocompatible

Question 13

When mixing a large polyanion with a large polycation, what kinetics would you expect?

Answer 13

2nd order

Question 14

Define chemisorption.

Answer 14

formation of a covalent bond upon collision with interface

Question 15

Define physisorption

Answer 15

formation of a noncovalent bond upon collision with surface

Question 16

What is the typical energy of a covalent bond?

Answer 16

50-150 kcal/mol

Question 17

What is the usual bond energy in physisorption?

Answer 17

1-10 kcal/mol

Question 18

What molecular characteristics maximize physisorption?

Answer 18

1) planar, 2) large, 3) amphiphilic, 4) opposite ionization state

Question 19

What are the therapeutic implications for protein adsorption?

Answer 19

1) unclear loss of therapeutic agent, 3) possible alteration of surface, 3) possible alteration of protein

Question 20

How are adsorbed proteins displaced?

Answer 20

ion/pH change or shaking

Question 21

How can protein adsorption be minimized?

Answer 21

1) minimize air/water interface, 2) make solid surfaces as hydrophilic as possible, 3) add an adsorption competitor

Question 22

Why should solid surfaces be hydrophilic regarding protein adsorption?

Answer 22

hydrophobic residues are at the core of protein. If container is hydrophobic, protein more likely to unfold and become an antigen.

Question 23

Define the Vroman Effect.

Answer 23

big proteins displace small proteins at a surface

Question 24

What are examples of adsorption competitors?

Answer 24

surfactants (Tweens & Brijs) or serum albumin

Question 25

What is HAS

Answer 25

human serum albumin

Question 26

What should be the concentration of a HSA to maximize rate of HAS adsorption?

Answer 26

1-2% w/v

Question 27

What kind of surface is air?

Answer 27

hydrophobic

Question 28

Why is it bad to displace adsorbed proteins?

Answer 28

precipitation and antigens

Question 29

What are the characteristics of proteins that maximize adsorption?

Answer 29

large, amphiphilic, flexible

Question 30

Describe the characteristics of chemisorption.

Answer 30

1) usually only at solid-liquid interfaces, 2) released as different molecule, 3) simple monolayers limits capacity

Question 31

What is an advantage to using glass a container?

Answer 31

SiO2 is inert to chemisorption

Question 32

Describe the characteristics of physisorption.

Answer 32

1) forms at variety of interfaces, 2) same molecular species when released, 3) multilayers can be formed

Question 33

What factors affect physisorption rate?

Answer 33

concentration of drug, number of unoccupied sites

Question 34

What is the volume of a minibag?

Answer 34

100 mL

Question 35

What are the various types of vaccines?

Answer 35

1) whole virus/microbe (attenuated or dead), 2) selected fraction, 3) synthetic protein

Question 36

What are the components of a vaccine?

Answer 36

1) antigen, 2) preservatives, 3) additives, 4) residues from manufacture, 5) adjuvants

Question 37

What are examples of preservatives?

Answer 37

phenol, 2-phenoxyethanol, thimerosal

Question 38

What are the functions of additives in vaccines?

Answer 38

stabilization of the live, attenuated virus to reduce virulence

Question 39

What are examples of additives in vaccines?

Answer 39

1) sugars (sucrose/lactose), 2) amino acids (glycine/glutamate), 3) proteins (gelatin/human serum albumin)

Question 40

In which vaccines are protein additives present?

Answer 40

MMR, shingles, rabies

Question 41

Advantages to using sugars as vaccine additives?

Answer 41

good if frozen, also good for isotonicity

Question 42

What kinds of manufacturing residues may be leftover in vaccines from manufacture?

Answer 42

inactivating agents, cellular components, antibiotics

Question 43

What are examples of inactivating agents used in manufacturing vaccines?

Answer 43

formaldehyde & glutaraldehyde

Question 44

What cellular components may be leftover in vaccines from manufacture?

Answer 44

chicken egg proteins (allergy), and yeast cells

Question 45

Why are antibiotics used in vaccine manufacture?

Answer 45

to prevent overgrowth during egg manufacture

Question 46

What kinds of antibiotics are used in vaccine manufacture?

Answer 46

streptomycin b, polymixin, amphoB

Question 47

What is the purpose of adjuvants in vaccines?

Answer 47

to potentiate the immune response

Question 48

How do adjuvants stimulate the immune response?

Answer 48

1) stimulate APCs and dendritic cells, 2) enhances adaptive immune response by unfolding protein to present epitope

Question 49

What are examples of adjuvants?

Answer 49

Al(OH)3, AlPO4, KAlSO4

Question 50

What do adjuvants not do?

Answer 50

1) directly induce the immune system, 2) irritate locally, 3) toxic

Question 51

How are parental products degraded?

Answer 51

1) hydrolysis, 2) oxidation, 3) photo, 4) deamidation

Question 52

What are common buffers?

Answer 52

1) ascorbate, 2) citrate, 3) phosphate, 4) bicarb, 5) acetate - painful

Question 53

What is the appropriate range of refrigerator temperatures according to USP?

Answer 53

2-8 degrees C

Question 54

What is the appropriate range of freezer temps according to USP?

Answer 54

-20 to -10 degrees C

Question 55

How are lyophilized products reconstituted?

Answer 55

with SWFI

Question 56

What drugs are susceptible to photodegradation?

Answer 56

nitroprusside, amphoB, furosemide

Question 57

How can deamidation be inhibited?

Answer 57

bulky amino acids around Arg to inhibit flexibility and through limiting H2O contact

Question 58

What factors affect hydrolysis?

Answer 58

1) pH, 2) temperature, 3) H2O

Question 59

For what temp increase does k double?

Answer 59

10 degrees C

Question 60

How can oxidation initiation be blocked?

Answer 60

1) limit O2, 2) use iron chelators and neutral pH to reduce co-factor contact, 3) limit H2O, 4) rid free radicles with ascorbic acid, 5) limit contact with light

Question 61

What are the 3 steps of free-radical reactions?

Answer 61

initiation, propagation, termination

Question 62

How does wavelength affect photodegradation?

Answer 62

shorter wavelength = higher energy = faster degradation