Exam 2 Flashcards

1
Q

Suspensions

A

type of dispersed system containing finely divided solid particles in water

insoluble drug particles suspended in solvent

thermodynamically unstable

particle size greater than 500nm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Dispersed phase

A

internal phase of suspensions (particles)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Dispersion medium

A

external phase of the suspension (solvent)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Examples of pharmaceutical suspensions

A

orally-administered mixtures
externally applied lotions
injectable preparations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why are suspensions useful?

A

Drugs with limited solubility in water (25-100 mg/mL)

taste-masking

improved chemical stability than solutions

longer-acting drugs; slower drug absorption from suspensions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Short (regular) insulin is a solution with a high efficacy after x hours?

A

2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Intermediate (NPH/long acting form) is a suspension with a high efficacy after x hours

A

4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Duration of NPR

A

less than 6 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Duration of NPH

A

up to 14 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Desirable characteristics of a suspension

A

adequate dispersion of particles in solvent

minimal aggregation/clumping of particles in suspension

prevent caking (formation of sedimentation that can’t be resuspended)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Formulation of a suspension has to be prepared such that it can be suspended upon?

A

moderate agitation/shaking

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

v= {d^2 x (pi-pe) x g} / 18n

A

stokes equation; relates sedimentation velocity to particle size and density, and solvent viscosity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

As solvent viscosity increases, sedimentation velocity…

A

decreases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the 2 key approaches to improve suspension stability

A

use a viscosifier: MC/HPMC

use a flocculating agents: electrolytes such as aluminum chloride, polymers, surfactants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Flocs

A

loosely bound particle clusters
stabilized by weak H-H bonds and van der Waals forces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Flocculated suspensions structure and redispersion

A

structure: scaffold-like, weak bonds

redispersion: easy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Deflocculated suspensions structure and redispersion

A

structure: closely packed, cake

redispersion: difficult/impossible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Suspending agent

A

increases viscosity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

wetting agent

A

disperse hydrophobic drug particles
decrease interfacial tension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Antioxidants

A

prevent oxidation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Buffers maintain

A

pH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Biologics

A

derived from biological organisms/biological material
have action specificity
require lower doses compared to traditional small molecule APIs
improved safety profile of protein drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How would you describe biologics approval over time?

A

steady rise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Major PO delivery factors of biologics

A
  1. high molecular mass means lower membrane permeability
  2. relative hydrophilicity/hydrophobicity balance
  3. ionic charge- function of proteins hydrophilicity and pH environment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

5 challenges to delivery of polypeptide drugs

A
  1. lower permeability across biological membranes
  2. lower solubility of hydrophobic proteins
  3. smaller molecular mass/particle diameter means rapid kidney clearance
  4. immunogenicity of recombinant proteins
  5. susceptibility to proteolytic degradation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Advantages of Oral protein and peptide delivery systems

A

protect drug from enzymatic degradation and decrease systemic clearance
increased cargo solubility
controlled release and minimize undesirable side effects
improve biodistribution, decrease non specific uptake
low immunogenicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

3 characteristics of PEGylated proteins

A
  1. increase in size to reduce kidney filtration
  2. increase in solubility due to PEG hydrophilicity
  3. decreased accessibility for proteolytic enzymes and antibodies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Pegylated protein advantages

A

sustained absorption
increased half life
decreased systemic clearance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How does PEGylation affect dosing?

A

decreases dosing intervals
increases patient compliance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are challenges for nucleic acid delivery?

A

hydrophilic molecules limit permeation into hydrophobic membrane
have a high molecular mass

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Short interfering RNA (SiRNA)

A

interferes with the translation of mRNA into a protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Vectors

A

carry nucleic acids to their sites of action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What are the extracellular steps in nucleic acid delivery?

A

circulation
accumulation
penetration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Intracellular steps in nucleic acid delivery

A

fusion
endocytosis
release
endo/lysome escape
nuclear localization
mRNA delivery
siRNA delivery
DNA delivery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What barriers can carriers overcome?

A

extracellular and intracellular barriers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Where are DNA drugs delivered?

A

nucleus

37
Q

Where are mRNA drugs and SiRNA delivered?

A

cytoplasm

38
Q

Gene therapy

A

clinical application of DNA molecules
replacement of mutated copy of the gene with a healthy/normal DNA copy

39
Q

What does ADA deficiency cause?

A

SCID

40
Q

What drives the need for safer alternative gene delivery?

A

limited packaging capacity of viral vectors and their immunogenicity

41
Q

What are the 3 main extracellular barriers/challenges to nanoparticle delivery of nucleic acids?

A

renal filtration
non-specific uptake by the liver/spleen
nuclease degradation

42
Q

What are the 3 main intracellular barriers/challenges to nanoparticle delivery of nucleic acids?

A

cellular entry
endosomal escape
nuclear uptake

43
Q

10-100 nm are useful as?

A

drug carriers

44
Q

Endosome

A

acidic compartments

45
Q

Polymers and lipids used for nanoparticle formation for nucleic acid delivery are ?

A

cationic chemical groups
amino groups are the most common

46
Q

What do amino groups in carriers bind to?

A

phosphate groups in nucleic acids

47
Q

What can go into a lipid nanoparticle?

A

DNA
siRNA
mRNA
Proteins
small molecules

48
Q

What does CAR stand for?

A

Chimeric Antigen Receptor

49
Q

CAR T-Cell Therapies

A

involve engineering the patient’s own immune cells to treat their cancer

50
Q

The CAR gene can be delivered to the patient’s T-cell using what?

A

a viral/non viral NP carrier

51
Q

What will CAR-T bind to ?

A

the patient’s cancer cell antigen

52
Q

CAR has improved over time for the?

A

Expansion of CAR-Ts after infusion
persistence of injected CAR-T

53
Q

What does the the extracellular domain of CAR do?

A

recognition/binding of a specific antigen by a T cell

54
Q

What does the intracellular domain of CAR do?

A

stimulate T-cell proliferation, cytolysis, and cytokine secretion to eliminate the target cell

55
Q

CD19

A

antigen present on cancer cells

56
Q

anti CD-19 CAR

A

binds to CD-19 on cancer cells

57
Q

Are CAR-T therapies patient specific?

A

yes

58
Q

Biological challenges of CAR-T therapies

A

on target toxicity; CAR-T struggles to tell the difference between normal and cancerous B cells
off target toxicity; cytokine release syndrome

59
Q

Manufacturing Challenges of CAR-T cell therapies

A

high cost
heterogeneity of personalized products

60
Q

What does Kymriah treat?

A

pediatric leukemia

61
Q

What does Yescarta treat?

A

adult B cell lymphoma

62
Q

How is ER different from IR dosage forms?

A
  1. maintains steady [drug] compared to immediate release dosage forms
  2. avoids fluctuations in plasma
63
Q

Eneteric polymers are usually polyacids with a pKa around?

A

5

64
Q

Which dosage forms are always coated with enteric polymers?

A

DR

65
Q

Purposes of DR dosage forms?

A
  1. protect the acid-sensitive API from degrading in the stomach
  2. protect stomach mucosa against the irritating effects of the drug
  3. local delivery effects in the small intestine
66
Q

Characteristics of ER systems

A
  1. prolong duration of drug release
  2. avoids fluctuations of [drug] and increases patient compliance
67
Q

controlled release membrane

A

mechanism where release of API is extended/ controlled over prolonged periods

68
Q

Diffusion mechanism

A

tablet core surrounded by ethyl/methyl cellulose asymmetric/porous membrane

water soluble portion of the membrane dissolves away leaving pores through which water and drug diffuse

69
Q

Dissolution based er drugs

A

dissolution of the polymetric matrix in addition to dissolution of the API molecules

70
Q

PLGA

A

poly(lacticacid)- co-glycolic acid

71
Q

Key factors that control the rate of drug release

A
  1. molecular mass of the PLGA polymer
  2. [API/drug] that’s loaded in the PLGA polymer matrix
72
Q

Osmotic release oral system

A
  1. GI fluid enters through semipermeable membrane, hydrates the push layer containing an osmogen
  2. Osmogen creates the osmotic pressure
  3. osmotic pressure is the driving force for zero-order drug release
73
Q

Factors affecting rate of drug degradation

A

temperature
pH
light intensity
excipients
solvents

74
Q

reaction rate

A

speed or velocity of the reaction
expressed in terms of changes in reactant/product concentration over time

75
Q

rate law

A

a quantitative relationship between the reaction rate and the concentration of reactants and other species present

76
Q

reaction order

A

describes the concentration dependence of a reaction rate on the concentration of reactants

77
Q

In a zero order reaction, rate is independent of?

A

concentration

78
Q

First order

A

rate = k [A]

79
Q

Second order

A

rate = k[A]^2 OR k [A][B]

80
Q

Third Order

A

rate = k[A]^2[B] or k[A][B][C]

81
Q

What type of dosage forms are useful to formulate high drug concentrations or drugs with limited water solubility?

A

suspensions

82
Q

As a drug solubilizes in solution, more drug is released so that concentration stays?

A

constant

83
Q

half-life

A

time it takes for a drug to decompose to half of its original concentration

84
Q

You should pick the R^2 value closest to which number?

A

1

85
Q

A0

A

starting/ initial [drug]

86
Q

K

A

rate constant

87
Q

shelf life

A

time a drug product is expected to remain within its approved specification

88
Q

t90

A

used to widely indicate shelf life