Pharmaceutics Flashcards
Which animal insulin is most similar to humans?
Porcine
How many amino acid differences are there between human and porcine insulin?
1
How many amino acid differences are there between human and bovine insulin?
3
How many amino acid differences are there between human and sheep insulin?
4
Who helped to solve the potency loss and solubility problems with insulin?
Walden
How did walden help to solve the potency loss and solubility problems with insulin?
Recognised the potent material was in a discarded precipitant. Led to process of isoelectric precipitation with standardised purity and potency
How was human insulin manufactured?
Combinations of A and B chains individually expressed in E. coli
Features of hexamer insulin?
Stable but not biologically active. Minimal diffusion into capillaries
Features of dimer insulin?
Biologically active but less stable then hexamer. Limited diffusion into capillaries
Features of monomer insulin?
Biologically active but not stable. Rapid diffusion into capillaries
What is NPH insulin?
Neutral protamine hagedorn
What causes NPH insulin to have a longer action?
Provided as a crystalline suspension of insulin with protamine and zinc
What is the only type of insulin which is typically cloudy?
Insulin NPH
Why is insulin NPH cloudy?
Due to added crystals
Why is zinc used in insulin?
Used as a delaying agent. Size of crystals is proportionate to duration of action
Why is insulin glargine long-acting?
One amino acid replaced by two a mini acids at the end of B chain.
Makes it more soluble at acid pH compared to physiological pH
Acid solution microprescipitates after injection due to reduced solubility
Crystals dissolve slowly to release insulin slowly
Why is insulin detemir long-acting?
One amino acid omitted from end of B chain and replaced with fatty acid.
Action is extended because it’s altered form make it stick to itself at the injection site.
Why is insulin lispro rapid acting?
Lysine and proline residues are switched on C-terminal of the B chain. Modification prevents dimers from forming so injection only contains monomers
How was insulin aggregation in continuous subcutaneous insulin infusions resolved?
Using less aggregating insulin such lispro
Inhaled insulin has a similar kinetic profile to what type of insulin?
Fast acting
Why was inhaled insulin removed from the market?
Poor sales volume due to cost
What is viscosity?
An expression of the resistance of a fluid to flow
What is a Newtonian fluid?
The viscosity does not change with the shear rate
Examples of Newtonian fluids?
Water
Honey
Pharmaceutical dosage forms with high water content