Question

a) Describe THREE (3) pharmacopoeial requirements of parenteral formulations. b) Outline the absorption rates of insulin to systemic circulation from “Actrapid® (insulin human)" and Novorapid® (insulin aspart). Your answer should explain the nature of the formulations that results in the absorption profiles observed.

Answer 1

A : Parenteral preparations may require

* the use of excipients such as solvent

* substances to enhance solubility

* suspending agents, buffering agents, substances to make the preparation isotonic with blood, stabilizers or antimicrobial preservatives. The addition of excipients is kept to a minimum.

B :The active substance in Actrapid, insulin human (rDNA), is produced by a method known as ‘recombinant technology’: the insulin is made by a yeast that has received a gene (DNA), which makes it able to produce insulin.

Upon injection into the SC tissue, insulin monomers and dimers are readily absorbed by blood capillaries [32]. Insulin hexamers, however, are not absorbed into the capillaries but can to some extent be absorbed by the lymphatic system due to their larger size.

In navorapid substitution of amino acid proline with aspartic acid at position B28 reduces the tendency to form hexamers as observed with soluble human insulin. Navorapid is there fore more rapidly absorbed from subcutaneous layer compared to soluble human insulin.