Galenics of Insulin, Softcover reprint of the original 1st ed. 1987
The Physico-chemical and Pharmaceutical Aspects of Insulin and Insulin Preparations

Galenical pharmacy or galenics is the science dealing with the pro­ duction of drug substances from raw materials, the purity of such substances, their formulation into pharmaceutical preparations with the desired effects and safety in use, and the quality control, stability and storage of the preparations. The field has taken its name from the Greek physician Galen (131-201 A.D.), who had a profound influence on medicine for many centuries because he collected and systematized the medicinal knowledge of his time. The discovery of insulin is attributed to Banting and Best who, in 1921, prepared an extract of the pancreas of the fetal calf and showed that the extract was capable of reducing the blood sugar level of a diabetic dog. This outstanding discovery gave rise to the rapid develop­ ment of the manufacture of insulin of bovine and porcine origin. By 1925, two Danish manufacturers of insulin preparations were established; both have since been in the forefront ofthe development of insulin preparations, the latest achievement being the marketing of human insulin by Novo in 1982. The development of highly purified human insulin produced semisynthetically from porcine insulin or by DNA recombinant methods are significant contributions to safe and efficient insulin therapy. Insulin is a protein which is destroyed in the gastrointestinal tract.

A. Production of Bovine and Porcine Insulin.- I. Introduction.- II. Physico-chemical Properties of Insulin Relevant to Production.- III. Production of Crystalline Insulin.- IV. Purification of Crystalline Insulin.- B. Characterization of Insulin.- I. Purity.- 1. Introduction.- 2. Gel Filtration.- 3. Disc Electrophoresis.- 4. Radioimmunoassay (RIA).- 5. High Performance Liquid Chromatography (HPLC).- II. Standardization.- 1. Bioassay Methods.- 2. Chemical Methods.- III. Immunogenicity of Insulin.- C. Insulin Preparations.- I. Introduction.- II. Pharmaceutical Chemistry.- 1. Insulin in Solution.- 2. Association of Insulin.- 3. Metal Ion Binding.- 4. Crystals and Crystallization.- 5. Chemical Reactions.- 6. Mechanisms of Prolongation.- III. Rapid-Acting Preparations.- 1. Introduction.- 2. Acid and Neutral Formulations.- 3. Manufacture.- 4. Absorption.- IV. Protracted Preparations.- 1. Introduction.- 2. Protamine Insulins.- 3. Insulin Zinc Suspensions (Lente Insulins).- 4. Binhasic Preparations.- 5. Other Types of Protracted Preparations.- V. Auxiliary Substances.- 1. Introduction.- 2. Preservatives.- 3. Isotonic Agents.- 4. Buffering Substances.- VI. Characterization and Testing.- 1. Introduction.- 2. Analytical Tests Applied to all Preparations.- 3. Analytical Control Specific for Special Preparations.- 4. Prolongation Tests.- VII. Insulin Strengths.- 1. Introduction.- 2. Strengths of Insulin Preparations.- VIII. Mixing Insulin.- 1. Insulin Mixtures.- 2. Dilutions.- 3. Addition to Intravenous Infusion Fluids.- IX. Stability.- 1. Physical Stability.- 2. Chemical Stability.- 3. Biological Stability.- 4. Immunogenicity Studies.- X. Storage and Use of Insulin.- 1. Storage.- 2. Withdrawal of Insulin from the Vial.- 3. Mixing Techniques.- 4. Preloading of Syringes.- XI. Insulin for Delivery Systems.- 1. Introduction.- 2. Use of Present Insulin Solutions in Infusion Pumps.- 3. Physical Stabilization of Insulin Solutions.- XII. Insulin Derivatives.- XIII. Alternative Administration of Insulin.- D. Human Insulin.- I. Manufacture.- 1. Sources.- 2. Conversion of Porcine Insulin.- 3. Biosynthesis in E. coli.- 4. Biosynthesis in Saccharomyces cerevisiae.- II. Preparations.- References.