Clinical challenges with excipients in insulin formulations and role of concentrated insulin

Abstract

Most of the insulin formulations in clinical use contain phenol, meta-cresol or both as excipients. These excipients in insulin preparations provide stability and have antimicrobial properties. However, they are reported to be associated with undesirable side-effects especially localised allergic reactions. Amount of excipients injected per unit dose of insulin is a major determining factor in causation of these reactions. This review discusses the excipients in different insulin formulations available in India with potential of precipitating undesirable effects and the use of concentrated insulins to reduce these complications. To avoid the detrimental effects associated with excipients, removal of preservatives or use of insulin preparations devoid of excipients can be an option. Besides these approaches, one approach that can be considered is the use of concentrated insulin to reduce the volume of insulin dose and thereby the excipients. Concentrated insulins address the high insulin requirements of the growing population of patients with type 2 diabetes who require higher insulin doses. Concentrated insulins help in reduction of dose volume as well as amount of excipients injected per unit dose of insulin. U200 (concentrated r-DNA Human Insulin Premix 30/70-200 IU/ml) can be advantageous with better absorption from smaller quantity injected, lesser variability in absorption, lesser pain and discomfort due to smaller quantity, lesser chances of hypoglycaemia all of which can lead to better patient compliance. Thus, concentrated insulin U200 can be one of the alternatives to prevent/reduce clinical complications with excipients in insulins.

One hundred years since insulin discovery: An update on current and future perspectives for pharmacotherapy of diabetes mellitus

“…Despite being a retrospective study with longitudinal limitations, confounding factors, noninclusion of indirect costs, the study still provides sufficient insights to advocate the consideration of other antidiabetics in combination with insulins in TIIDM, to provide optimal efficacy 19 . Insulins are associated with adverse effects of hypoglycaemia, lipodystrophy, insulin resistance, urticaria, angioedema, swelling, erythema, stinging at the injection site and oedema 20 . Modi et al .…”

“…reported that the latter reactions, when seen with human insulins, may be due to the presence of excipients such as phenol and meta‐cresol. The use of highly concentrated insulins might reduce the concentration of the latter excipients and thereby reduce the risk of allergic reactions 20 …”

“…The use of highly concentrated insulins might reduce the concentration of the latter excipients and thereby reduce the risk of allergic reactions. 20 Insulin analogues consist of ultra-short insulins such as lispro, aspart and glulisine, and ultra-long insulins such as glargine, detemir and degludec. 21 A biosimilar of lispro and glargine have been recently approved, which are admelog and basiglar, respectively.…”

The effect of intravenous maropitant on blood pressure in healthy awake and anesthetized dogs

“…Currently, there is no literature that documents the blood pressure effects of metacresol injection in veterinary medicine. Reported side effects of metacresol in human medicine include localized allergic skin reactions, l cytotoxicity to fibroblast cell, human adipocyte, and monocytic cells [41][42][43]. Further investigation is needed to evaluate the effect of metacresol on blood pressure.…”

Structural, Thermal, and Storage Stability of Rapana Thomasiana Hemocyanin in the Presence of Cholinium-Amino Acid-Based Ionic Liquids

“…In view of their pharmaceutical application, novel non-toxic excipients that are able to preserve the structure and activity of proteins and enzymes in a solution are yet on-demand for clinical practice. For example, still most of the insulin formulations in clinical use contain the toxic phenol, m-cresol, or both excipients [ 34 ]. Dimethyl sulfoxide or dimethylacetamide are used to reduce the viscosity of immunoglobulin G1.…”