Conventional Preparations of Insulin

CONVENTIONAL PREPARATIONS OF INSULIN

The conventional commercial preparations are produced from beef and pork pancreas. They contain ~1% (10,000 ppm) of other proteins (proinsulin, other polypeptides, pancreatic proteins, insulin derivatives, etc.) which are potentially antigenic. In the developed countries, these have been totally replaced by highly purified pork insulins/recombinant human insulins/insulin analogues. However, because of low cost, conventional preparations are still used in India and many developing countries. The types of insulin preparations are tabulated in Table 19.1.

Regular (Soluble) Insulin:

It is a buffered solution of unmodified insulin stabilized by a small amount of zinc. At the concentration of the injectable solution, the insulin molecules self aggregate to form hexamers around zinc ions. After s.c. injection, insulin monomers are released gradually by dilution, so that absorption occurs slowly. Peak action is produced only after 2–4 hours and action continues upto 6–8 hours. The absorption pattern is also affected by dose; higher doses act longer. When injected s.c. just before a meal, this pattern often creates a mismatch between need and availability of insulin to result in early postprandial hyperglycaemia and late postprandial hypoglycaemia. Regular insulin injected s.c. is also not suitable for providing a low constant basal level of action in the inter-digestive period.

To overcome the above problems, some longacting ‘modified’ or ‘retard’ preparations of insulin were soon developed. Recently, both rapidly acting as well as peakless and longacting insulin analogues have become available. However, after i.v. injection, the hexameric regular insulin dissociates rapidly to produce prompt action.

For obtaining retard preparations, insulin is rendered insoluble either by complexing it with protamine (a small molecular basic protein) or by precipitating it with excess zinc and increasing the particle size.

Lente Insulin (Insulin zinc Suspension):

Two types of insulinzinc suspensions have been produced. The one with large particles is crystalline and practically insoluble in water (ultralente or ‘extended insulin zinc suspension’). It is longacting. The other has smaller particles and is amorphous (semilente or ‘prompt insulin zinc suspension’), is shortacting. Their 7:3 ratio mixture is called ‘Lente insulin’ and is intermediate acting.

Isophane (Neutral Protamine Hagedorn Or NPH) Insulin:

Protamine is added in a quantity just sufficient to complex all insulin molecules; neither of the two is present in free form and pH is neutral. On s.c. injection, the complex dissociates slowly to yield an intermediate duration of action.

Protamine Zinc Insulin (PZI):

It contains excess of protamine, so that the complexed insulin is released more slowly at the site of s.c. injection and a long-acting preparation results. It is rarely used now.

1. Regular insulin: SOLUBLE INSULIN 40 U/ml, 100 U/ml, for s.c. or i.v. injection.

2. Lente insulin (insulin zinc suspension) 7:3: LENTE INSULIN 40 U/ml for s.c. inj.

3. Neutral protamine Hagedorn (NPH) insulin: ISOPHANE (NPH) INSULIN 40 U/ml for s.c. inj.

4. Protamine zinc insulin: PROTAMINE ZINC INSULIN 40 U/ml for s.c. inj.