Topic 2K Peptides And Protiens

Question 0

Describe the physical and chemical instability of pharmaceutical proteins (8)

Answer 0

1. Physical instability:
   - elevated temperatures->denaturation of proteins in aqueous solution
   - low temperatures-> may also induce destabilisation
   - protein aggregation
   - aggregate due to shaking or exposure to shear forces
2. Chemical instability
   -prevention of all chemical degradation reactions is difficult due to the
   many amino acids involved
   -deamidation: is common in water (degradation)
   -oxidation
   -isomerization
   -lots of amino acids involved

Question 1

What are the special challenges that pharmaceutical proteins offer to the pharmaceutical formulator (7)

Answer 1

**1. Many functional groups (large, delicate molecules)
2. Readily and irreversibly changed
3. Pharmacokinetic characteristics
Eg: clearance or immunogenicity
4. Their epithelial penetration capability is very low
5. Administered only parenterally

Question 2

Excipients used in the formulation of pharmaceutical proteins for parenteral administration. (Include an example of each excipient) (9)

Answer 2

1. Amino acids: Lysine
2. Detergents: Polysorbate
3. Chelating agents: EDTA
4. Antioxidants: Sulphites
5. Lyoprotectant: Sugar
6. Preservatives: Phenol
7. Buffer components: Citrates, phosphates
8. Osmotic agents: NaCl sugars

Question 3

Describe 3 approaches that have been followed to improve bioavailability of pharmaceutical proteins (3)

Answer 3

1. Co-administration of protease inhibitors to slow degradation
2. Excipients added to enhance passage through epithelial barriers
3. Prolong presence of the protein at the absorption surface

Question 4

Describe the manufacture of the first genetically engineered vaccine (May use suitable illustrations) (10)

Answer 4

The first genetically engineered vaccine was for hepatitis B.
It was through recombinant DNA technology that this was achieved.
It uses a synthetic copy of the viruses protein coat to fool the bodies immune system into mounting a response.
This minimises the risk of causing the disease.
Recombinant hepatitis B vaccine has demonstrated an ability to induce antibody-to-hepatitis B surface antigens.

See pic