Pharmaceutics - De Bank Flashcards
What is the main driving force of protein folding?
Hydrophobic interactions
What are the 4 main types of things that cause chemical changes to proteins?
Deamidation –> Asparagine and glutamine residues
Oxidation –> Trace amounts of chemical oxidants/transition metals can cause this for His, Met, Cys, Trp and Tyr residues
Hydrolysis –> Mainly of X-Asp-Y
Disulphide formation/exchange –> Removing terminal disulphide bond will decrease Tm by 40 degrees
What excipients are added to therapeutic proteins?
Solubility enhancers
Anti-absorption and anti-aggregation agents
Buffereing agents
Preservatives/anti-oxidants
Cake formers
Osmotic agents
Why do we want a layer of hydration around proteins?
To prevent solutes from interacting with the protein
What role can cyclodextrins play in the formulation of therapeutic proteins?
Suppress the aggregation of proteins
What are polysorbates?
Amphiphillic emulsifyers that are used in protein formulation
They stabilise proteins via…
- Exclusion of solutes
- Act as a chemical chaperone to aid protein refolding
- Binding to hydrophobic patches of proteins
How can polysorbates cause protein aggregation/denaturation?
They get auto-oxidised (hydrolytic degradation) to reactive peroxides and aldehydes (increasing immunogenicity)
What has the greatest effect on polysorbates?
Light exposure
What is lyophilization?
Freeze drying of drugs at low temepratures (in liquid form)
Require reconstitution to administer
Lots of time for microbial contamination (compared to standard liquid preperations)
It takes time for full dissolution to occur
What is the main disadvantage of IV administration?
Dose is prefilled into an IV bag with a dilutent, but adsorption of this can cause a lower concentration to be achieved
So we must minimise interfaces, to prevent aggregation
What are some of the advantages and disadvantages of SC administration?
Advantages –> Use of an autoinjector can occur
No compounding needed at the pharmacy
Disadvantages –> Maximum dose/volume is lower (compared to IV)
BA is less than 100%
In terms of using protein delievery in pMDIs, what are proteins not stable in?
Organic solvents (eg, HCFCs)
What is the main advantage of intravitreal administration?
100% bioavaliability
What is Entaracept (Enbrel)?
A TNF(a) antagonist
A fusion protein
A dimer –> so can bind to 2 molecules of TNF(a)
When does insulin form hexamers?
In the prescence of Zinc ions
What is the difference between long and fast acting insulin?
Long Acting –> Promote the formation of a hexamer, which redues solubility and promotes protein binding
Fast Acting –> Prevents the formation of hexamers and dimers, which increases the solubility
What are the benefits of PEGylating proteins?
Hydrophillicity –> Improves solubility and increases BA
Flexibility –> Reduced toxicity and increases stability
Attatchment of other drugs/targeting ligands
Decreases renal clearance –> As it can fit through pores!
What is Spray Drying?
A continous proccess where powders are formed (without the need for milling/sieving)
Can be aseptically
How do we get hydrophillic biologicals into polymeric systems?
W/O emulsion –> electrospinning
W/O/W –> micro/nanoparticles
How could you increase nasal insulin administration?
Reverse micelle formation by sodium deoxycholate
What are the 4 different types of microneedles that could be used for transdermal insulin delivery?
Poke and Patch
Coat and Poke
Poke and Release
Poke and Flow
What are the 6 different types of controlled drug release that these graphs depict?
What are the 3 different types of Long-Term Release drugs?
Bulk Erosion –> Its hydrolysed over time, decreasing over time
Surface Erosion –> Water erodes the outside
Diffusion –> The polymer doesn’t degrade
What are 3 stimuli that will cause insulin release in controlled drug delievery systems (CDDS)?
Increase in glucose –> causing glucose oxidase levels to increase
High levels of glucose bind to Phenylborinc Acid (PBA)
Glucose competitively binds to Concanavalin A (ConA)
How does tissue engineering occur?
Cell isolation
Expansion of cell numbers
Seeding on a suitable scaffold
Maturation of the tissue
Implantation in the patient
What’s the aim of tissue regeneration?
Promoting the healing of the bodies cells by acitivating the bodies own repair mechanisms
Provides a scaffold for the body to work with
