Exam 3 Flashcards
How is polydispersity calculated?
Mw/Mn
Find the average number and weight of Batch 1:
2 Polymers with MW of 50 kDa
10 Polymers with MW of 20 kDa
Mn=25 kDa
Mw=30 kDa
(Mono/poly-dispersed) When the molecular weight distribution equals 1
Monodispersed
(Lower/Higher) polydispersity= Broader distribution
Higher
(Mono/poly-dispersed) When the molecular weight distribution is greater than 1
Polydispersed
Crystalline or Amorphous: linear polymer with a good barrier to drug diffusion
Crystalline
Crystalline or Amorphous: What does this tell about its melting point?
Crystalline: definable melting point, sharp Tm
In Crystalline polymers, the polymer can pack together in regular arrays at T (>,<, =) Tm
In Crystalline polymers, the polymer can pack together in regular arrays at T<Tm
Crystalline or Amorphous: Polymers with irregular structure
Amorphous
Crystalline or Amorphous: Define what occurs at points a and b
Amorphous:
a- low temp, rigid “glass” structure
b- high temp, rubbery
Crystalline or Amorphous: Polymer forms “glass” at T<Tg
Amorphous
Crystalline or Amorphous: Softens over a wide temperature range
Amorphous
With Amorphous (Tg), At T(<,>, =)Tg
Polymers are hard, stiff, and glassy
T<Tg
With Amorphous (Tg), At T(<,>, =)Tg
Polymers are rubbery and may flow
T>Tg
A long polymer with bulky side chains has a (higher/lower/no change) Tg
higher Tg
T/F: The less crosslinked, the higher Tg
False: more crosslinked
Molecules that increase the entropy and mobility of the polymer chains
Plasticizers
Rate the modulus of a, b, and c
a- high modules
b- low modules
c- Very low modules
What is the area under the curve (arrow) referred to as?
Toughness
T/F: Stress (force/area) is proportional to strain (deformation)
True
T/F: Elastic polymers are highly crosslinked
True
Swell rapidly when places in water and retain large volumes of water in their structures
hydrogels
Chemical and physical gels of hydrophilic polymers are ______________
crosslinked
Which are cellulose-based polymers:
-Alginic acid
-Carboxylmethyl cellulose
-Poly(vinyl alcohol)
-Ethylcellulose
-Hydroxypropyl methyl cellulose
-Polyactic acid
-Ethylcellulose
-Carboxylmethyl cellulose
-Hydroxypropyl methyl cellulose
Which are hydrocolloids (hydrophilic polymers)?
-Alginic acid
-Carboxymethyl cellulose
-Chitosan
-Polylactic acid
-Ethylcellulose
-Alginic acid
-Chitosan
Which are water-soluble synthetic polymers?
-Poly(ethylene glycol)
-Poly(lactic-co-glycolic) acid
-Polylactic acid
-Poly(vinyl alcohol)
-Poly(ethylene glycol)
-Poly(vinyl alcohol)
Which are water-soluble synthetic polymers?
-Poly(ethylene glycol)
-Poly(lactic-co-glycolic) acid
-Polylactic acid
-Poly(vinyl alcohol)
-Poly(lactic-co-glycolic) acid
-Polylactic acid
What does the stratum corneum consist of?
Dead cells (bricks) and lipid (mortar)
T/F: Dead cells are non-permeable
True
T/F: Dead cells are non-permeable
True
This layer of skin composes of non-vascularized living cells without capillaries. It is the source of skin color and tanning.
Viable epidermis
Dermis
Viable epidermis
How does the viable epidermis get nutrients?
Diffusion from dermis
This layer of skin contains capillaries. Drugs reaching these capillaries can achieve a systemic effect. Pain, thermal and tactile sensors are here.
Viable epidermis
Dermis
Dermis
What is the pH of the skin? Why?
Around 5. This inhibits the growth of bacteria.
Medications derived from or produced by living organisms
Biologics
What is the biggest class of biologics?
A. Cytokines
B. Monoclonal antibodies (MAbs)
C. Vaccines
B. Monoclonal antibodies (MAbs)
The hinge region of MAb consist of what type of bonds?
A. Hydrogen bonds
B. Phosphodiester bonds
C. Disulfide bonds
C. Disulfide bonds
What region is characterized by the bracketed upper portion?
Fab - Variable portion
Where does antigen binding occur?
On N (The CDR) in the variable portion
Which area determines the biodistribution and plasma half-life?
C (Constant) region
What part of the Antibody-Drug Conjugate (ADC) is designed to kill target cells when internalized and released?
Antibody
Cytotoxic agent
Linker
Cytotoxic agent
What part of the ADC does the cytotoxic agent attach to the antibody? It typically is fragile and is protected by freeze drying.
Linker
Which biologics is characterized by alpha and beta chains linked by Disulfide bonds in an alpha helical structure?
Insulin
Which is a fast acting insulin analog that has Lys and Pro on C-terminus of B-chain reversed, blocking the formation of dimers and hexamers?
Lispro insulin (Humalog, Lilly)
Insulin aspart (Novolog, Novo Nordisk)
Insulin glargine
Lispro insulin (Humalog, Lilly)
Which is a fast acting insulin analog with a Pro on C-terminus or B-chain mutated to Asp?
Lispro insulin (Humalog, Lilly)
Insulin aspart (Novolog, Novo Nordisk)
Insulin glargine
Insulin aspart (Novolog, Novo Nordisk)
Which is a long-acting insulin with Asn at A21 mutated to Gly, two Arg added to C-terminus of B-chain?
Lispro insulin (Humalog, Lilly)
Insulin aspart (Novolog, Novo Nordisk)
Insulin glargine
Insulin glargine
What are characterized as the first “living drugs” that are engineered T-cells for cancer immunotherapy?
CART-cell therapy
How are most biologics administered?
Parenterally
What makes solution formulations popular?
Simplest (no reconstitution)
least expensive
inspected visually
What are clinical concerns regarding biologic solutions?
(PISSED)
Pain on Injection
Sterility
Side Effect (Dose-limiting immune response)
What is a good pH for injections?
8
What are the three ways proteins aggregate?
Chemical reaction- antigens attach together or fold slightly detached
Colloidal interactions- stacking
Unfolding- expose hydrophobic domains which can lead to chemical stacking and illicit immune responses
Why should you not shake a formulation solution?
Shaking increases surface area and increases contact with the surface of the container
Which portion of the container is worst for the agitation of formulations?
The three-phase boundary
Which is stabilized? Destabilized?
Left is destabilized, Right is stabilized
Excipients that (preferential binding/preferential excluded) from the protein surface promote interactions with water and stabilize native protein structure
preferential excluded
Excipients that bind to the protein can lead to what type of unfolding?
denaturation
T/F: Prefilled syringes, pens and autoinjectors are easy to use formulations
F: Not formulations but combination products
What are disadvantage of pre-filled syringes that involve its packaging?
- Drug waste due to priming
- Greater surface-to-volume ratio, presence of lubricants, can induce aggregation of protein drugs
Label the numbers:
finger grip, gasket, plunger, luer lock
syringe barrel, top cap
- Syringe barrel
- Luer lock
- Finger grip
- Plunger
- Gasket
- Top cap
When compared to vials containing solutions for injection, these devices have a (lower/higher) surface-to-volume ratio and (lower/higher) total volume.
When compared to vials containing solutions for injection, these devices have a higher surface-to-volume ratio and lower total volume.
Proteins are __________ and can unfold when exposed to surfaces or interfaces.
surfactants
Syringe lubricants that coat the inside of a barrel surface are typically (hydrophilic/hydrophobic)
hydrophobic
What makes pre-filled syringes more susceptible to surface area?
-Lubrication on the barrel surface
-Oil droplets suspended in the solution
How do folded, native proteins become aggregates?
hydrophobic domain inside of hydrophobic shell allows protein to split so hydrophobic domain is attached to hydrophobic surface. These partially unfolded proteins form dimers that aggregate
Which is the biggest advantage of lyophilized powders?
- Reconstituted allowing more convenience
- Cheaper
- Reduced chemical and physical degradation
- Refrigeration maintaining freshness
- Reduced chemical and physical degradation
(all others are false)
What are the two disadvantages of lyophilized powders?
-Must be reconstituted prior to injection
- More expensive due to time consuming manufacturing
Lyophilization removes _____ by the process of ______ which occurs at (low/high) temp and (low/high) pressure.
Lyophilization removes water by the process of sublimation which occurs at low temp and low pressure.
What order occurs in the process of lyophilization?
Sublimation
Vacuum
Freezing
Dry powder to ambient
Freezing, Vacuum, Sublimation, then Dry powder to ambient
How can lyophilization cause instability?
Freeze-conc can promotes aggregation
