Exam 3 - Advanced Pharmaceutical Dosage Forms Flashcards
(16 cards)
Describe the structure of peptide drugs
- Basic structure: a chain of amino acids (<50 amino acids)
- Written from N-terminus to C-terminus
Name the key advantage of using solid phase synthesis for peptide drugs
can use non-natural modification (e.g non-natural AAs, etc)
Explain the process of solid phase synthesis of peptide drugs
- start with a compound and couple it with a protecting group
- where the protective group will leave
- from there you can add another AA with a protecting group
- where the protective group will leave, but the AA will stay
- two options can happen:
compound is cleaved
or continually added AA with protecting groups
Explain the key challenge with non-enzymatic peptide synthesis
- coupling yields needs to be extremely high, for a long linear synthesis
- yields for consecutive reactions need to be multiplied
- best way to synthesis is via parallel pathway
Describe the basic structure of protein drugs
a longer amino acid chain with secondary structure (>50 amino acids)
When is a protein considered a drug by the FDA?
When it has > 40 amino acids
Explain why compounding biologics not allowed
- proteins are FRAGILE → congregation
- this causes compounding biologics to destroy activity, destroy bioavailability, or even cause toxicity
How are protein drugs manufactured?
produced via biosynthesis
During the manufacturing process of protein drugs, there are probes for what characteristics?
- pH (most effective)
- dissolved oxygen
- temperature
- pressure
- biomass
- carbon source
Describe post-translational modification (PTM)
chemically modify the protein to alter its function, localization, stability, or interactions (without changing the AA sequence) = Biosimilar (structures are very similar, but not identical)
List different types of PTM
- Me: Methylation
- Ac: Acetylation
- P: Phosphorylation
- Su: SUMOylation
- Ub: Ubiquitination
- OH: Hydroxylation
- S-S: Disulfide bond
- Lipidation
- Glycosylation
Describe “simple mutation”
Change the actual sequence of nucleotides in DNA, leading to a different mRNA and potentially different AAs
List conditions that can lead to protein degradation
- High temperature
- Freeze-thaw: physical degradation (aggregation)
- Agitation
- Low OR High pH
- Forced deamidation: get rid of ammonia and make carboxylic acid
- Oxidation
- Photostability: exposure to light (crosslinking)
How do protein/peptide drugs degrade?
- Degradation pathways with disulfide exchange
- The disulfide bonds shuffle and move around, which causes the structure to unfold (protein aggregation and denaturation)
Describe physical degradation
- non-covalent changes
- denature proteins
- affects protein folding/aggregation (but no alteration of AA sequence)
Describe chemical degradation
- changes the PHYSICAL structure of the protein (involved covalent modifications)
- can lead to physical degradation
