New routes of administration for insulin
Insulin
- Peptide hormone
- Regulation of carbohydrate blood levels and metabolism
- Insulin causes a.o. liver, muscle and fat cells to take up glucose as glycogen or as
triglycerides
- Insulin is produced by the pancreas as a reaction to a raise in blood glucose levels
(e.g. after food intake).
- To prevent hypo-glycaemia, there is a rapid decrease (metabolization) of insulin after
insulin has done its work
Diabetic patient type I
- No insulin production at all when glucose levels are high
- Maintenance of basal insulin levels between meals and during the night (basal
insulin)
- To generate insulin blood level peaks during/shortly after the meal adapted to the
carbohydrate intake. (pre-prandial insulin)
- Imitate natural insulin levels and profile in blood
Diabetic type II
- Still insulin production but an insufficient reaction of the body to insulin
- Generate peak levels of insulin as reaction to the meal. (pre-prandial insulin)
- Type II does have a basal insulin.
Substance insulin
- A-chain 20 amino acids
- B-chain 31 amino acids
- Between the chains two cysteine bridges
- One internal cysteine bridge in the A-chain
- 5805 Da
- Forms easily dimers and hexamers (induced by zinc ions)
Source of insulin
- Past: from the pancreas of pigs/cattle
- Now: production from recombinant micro-organisms (E. coli, S. cerevisiae)
Properties relevant to administration and dosage form
- 5808 Da
- Diameter = 2.2 nm
- Unstable in solution (fridge)
- Tendency for aggregation in solution (dimers and hexamers)
- Broken down by enzymes in the gastro-intestinal tract (proteolytic enzymes)
- Too large to pass membranes, except of the alveoli membrane.
, Subcutaneous injection
advantages disadvantages
High bioavailability (>90%) Sterile
Control of dose Pain
Dose flexibility Ableness to inject
Fast effect Expensive
Long acting (depot) possible Fridge required
Not released in the portal vein
Slow uptake in the circulation
1. Injection pen
advantages disadvantages
“Easy” to use Injection
Precise and flexible dosing Sterile
Low change for dosing errors More times a day
Thin needle Simulation of natural plasma profile is
Reproducible injection depth difficult
Insulin in solution (fridge) Fridge
2. Insulin pump
indications disadvantages
poor control of blood sugar Mechanically fragile
aware of hypoglycemia Blockage of tubing
history of severe hypoglycemia expensive
For pregnant women
irregular lifestyle
low insulin requirements
Fast acting insulin
- pre-prandial insulin
- fast onset, rapid acting
- limit duration of the effect
- Change the amino acid sequence to prevent dimers being formed. Dimers cause a
decreased diffusion rate.
- Insulin aspart (NovoRapid): B-28 proline aspartic acid
- insulin glulisin (Apidra): B-3 aspartic acid lysine and B-29 lysine glutamic acid
- insulin lispro (Humalog): B-28 proline B-29 lysine
intermediate acting
- complex of insulin with protamine (and some zinc)
- amorphous hexamer of zinc-insulin
Long actin insulin
- basal insulin
- Slow dissolution rate
- Zinc insulin, crystalline: Crystalline hexamer of zinc-insulin
- Insulin Glargine (Lantus):
Insulin
- Peptide hormone
- Regulation of carbohydrate blood levels and metabolism
- Insulin causes a.o. liver, muscle and fat cells to take up glucose as glycogen or as
triglycerides
- Insulin is produced by the pancreas as a reaction to a raise in blood glucose levels
(e.g. after food intake).
- To prevent hypo-glycaemia, there is a rapid decrease (metabolization) of insulin after
insulin has done its work
Diabetic patient type I
- No insulin production at all when glucose levels are high
- Maintenance of basal insulin levels between meals and during the night (basal
insulin)
- To generate insulin blood level peaks during/shortly after the meal adapted to the
carbohydrate intake. (pre-prandial insulin)
- Imitate natural insulin levels and profile in blood
Diabetic type II
- Still insulin production but an insufficient reaction of the body to insulin
- Generate peak levels of insulin as reaction to the meal. (pre-prandial insulin)
- Type II does have a basal insulin.
Substance insulin
- A-chain 20 amino acids
- B-chain 31 amino acids
- Between the chains two cysteine bridges
- One internal cysteine bridge in the A-chain
- 5805 Da
- Forms easily dimers and hexamers (induced by zinc ions)
Source of insulin
- Past: from the pancreas of pigs/cattle
- Now: production from recombinant micro-organisms (E. coli, S. cerevisiae)
Properties relevant to administration and dosage form
- 5808 Da
- Diameter = 2.2 nm
- Unstable in solution (fridge)
- Tendency for aggregation in solution (dimers and hexamers)
- Broken down by enzymes in the gastro-intestinal tract (proteolytic enzymes)
- Too large to pass membranes, except of the alveoli membrane.
, Subcutaneous injection
advantages disadvantages
High bioavailability (>90%) Sterile
Control of dose Pain
Dose flexibility Ableness to inject
Fast effect Expensive
Long acting (depot) possible Fridge required
Not released in the portal vein
Slow uptake in the circulation
1. Injection pen
advantages disadvantages
“Easy” to use Injection
Precise and flexible dosing Sterile
Low change for dosing errors More times a day
Thin needle Simulation of natural plasma profile is
Reproducible injection depth difficult
Insulin in solution (fridge) Fridge
2. Insulin pump
indications disadvantages
poor control of blood sugar Mechanically fragile
aware of hypoglycemia Blockage of tubing
history of severe hypoglycemia expensive
For pregnant women
irregular lifestyle
low insulin requirements
Fast acting insulin
- pre-prandial insulin
- fast onset, rapid acting
- limit duration of the effect
- Change the amino acid sequence to prevent dimers being formed. Dimers cause a
decreased diffusion rate.
- Insulin aspart (NovoRapid): B-28 proline aspartic acid
- insulin glulisin (Apidra): B-3 aspartic acid lysine and B-29 lysine glutamic acid
- insulin lispro (Humalog): B-28 proline B-29 lysine
intermediate acting
- complex of insulin with protamine (and some zinc)
- amorphous hexamer of zinc-insulin
Long actin insulin
- basal insulin
- Slow dissolution rate
- Zinc insulin, crystalline: Crystalline hexamer of zinc-insulin
- Insulin Glargine (Lantus):
