Insulin product formulation

Insulin is the one agent that can be used in all forms of DM for blood sugar control. Insulin is the essential treatment for patients with type 1 DM and can overcome insulin resistance in patients with type 2 DM. Insulin is available commercially in various formulations that vary markedly in terms of onset and duration of action and the source from which a product is obtained. Insulins can be divided into four separate classes based on their length of action. Most formulations are available as U-100, indicating a concentration of 100 units/mL. Insulin is typically refrigerated, and most vials are good for 28 days at room temperature. Specific details of insulin products are listed in Table 40-9. 

The most common pancreatic disease requiring pharmacologic therapy is diabetes meliitus, a deficiency of insulin production or effect. Diabetes is treated with several formulations of insulin (all administered parentertdly at present) eind with four types of oral antidiabetic agents (Figure 41-1). 

A CZE method for the separation of insulin and its deamidation products with untreated fused-silica capillaries using a run buffer containing 2-(A-cyclohexyl-amino) ethanesulfonic acid (CHES), triethylamine, and 10% acetonitrile has been reported [90]. This system separated acidic and neutral desamido-insulin in formulated human insulin with the relative standard deviation (RSD) of the migration times <1%, whereas RP-HPLC coeluted the neutral desamido-insulin with insulin. Sergeev et al. described an analytical scheme for monitoring recombinant human... 

In 1992, Drejer et al. [31] investigated the pharmacokinetics of intranasal insulin containing a medium-chain phospholipid (didecanoyl-L-alpha-phosphatidylcho-line) as absorption enhancer in 11 normal volunteers. Intranasal insulin was absorbed in a dose-dependent manner with a mean plasma insulin peak 23 7 min after administration. Mean plasma glucose nadir was seen after 44 6min, 20min after intravenous injection. Moreover, intranasal administration of insulin resulted in a faster time-course of absorption than subcutaneous injection, and the bioavailability for the nasal formulation was 8.3% relative to an intravenous bolus injection when plasma insulin was corrected for endogenous insulin production estimated by C-peptide. 

Actrapid/Velosulin/ Monotard/ Insulatard/ Protaphane/ Mixtard/ Actraphane/ All contain recombinant human insulin produced in S. cerevisiae formulated as short/ intermediate/long acting product) Identical to native human insulin Novo Nordisk 2002 (EU)... 

Biotechnology-derived products have led to renewed interest in establishing reference standards based on the same bulk of material. Thus a single formulation, assay, and reference standard may be the fact worldwide. This situation can become complex such as with insulin where both biotechnology-derived insulin and animal-source insulin are in the marketplace at the same time. 

Systemic absorption of pulmonary-deUvered peptides and proteins has been the objective of many investigations [2]. The most successful work in this field is the development of insulin formulations for inhalation.These dosage forms might, in the near future, become a suitable alternative for the current subcutaneous injection of insulin that is used to obtain meal-time glucose control [3]. In spite of the strict requirements regarding dose variability for insulin, the pulmonary products under development seem to be as safe as the subcutaneous injections. 

Many successful protein products, including antibodies, have been marketed over the years for the treatment of a number of diseases. One of the oldest examples of a protein product is insulin, still one of the most successful drugs after 70-80 years of its discovery. Early insulin preparations, derived from natural sources, are being replaced by recombinant human insulin preparations and new formulations are being marketed that provide a more gradual and continuous release profile and maximise glucose control in diabetic patients. " ... 

Although no biopharmaceutical product delivered to the bloodstream via the pulmonary route has been approved to date, several companies continue to pursue active research and development programmes in the area. Amongst the leading product candidates is Exubera , an inhalable dry powder insulin formulation currently being evaluated by Pfizer and Aventis Pharma in Phase III clinical studies. The inhaled insulin is actually more rapidly absorbed than if administered subcutaneously and appears to achieve equivalent glycaemic control. While promising, final approval or otherwise of this product also depends upon additional safety studies which are currently under way. 

---