Insulin formulation parenteral

D Souza, R., Mutalik, S., Venkatesh, M., Vidyasagar, S., and Udupa, N. (2005), Nasal insulin gel as an alternative to parenteral insulin Formulation, preclinical and clinical studies, AAPS PharmSciTech., 6, E184-E189. 

Lecithins are also used in suppository bases, to reduce the brittleness of suppositories, and have been investigated for their absorption-enhancing properties in an intranasal insulin formulation. Lecithins are also commonly used as a component of enteral and parenteral nutrition formulations. 

Perhaps the most well-known example of a parenteral suspension formulation is insulin. Many insulin formulations also take advantage of the different physical forms which can be produced when insulin is complexed with zinc. Suspensions of the amorphous form of insulin zinc have a faster onset of action and shorter duration of action compared to those of the crystalline form. In order to provide both a rapid onset and a long duration of action, many formulations are composed of a mixture of amorphous and crystalline zinc insulin. 

The objectives of the present chapter are to provide a brief overview of the complexity and diversity of insulin formulation, to give a historical review of the efforts to improve parenteral delivery of insulin, and, with an emphasis on the last 25 years efforts, to survey the numerous studies performed in a search for acceptable insulin delivery through various noninvasive routes. 

Protein-based drugs have been formulated mainly as stable liquids or in cases where liquid stability is limiting as lyophilized dosage forms to be reconstituted with a suitable diluent prior to injection. This is because their delivery has been limited primarily to the parenteral routes of intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration. There are a few drugs that have been developed for pulmonary delivery, such as rhDNase (Pulmozyme ) and an inhalable formulation of insulin (e.g., Exubra ). However, even such drugs have been formulated as either liquid or lyophilized or spray-dried powders. This chapter will focus only on excipients that are applicable to liquid and lyophilized protein formulations. 

Insulin preparations that are commercially available differ in their relative onset of action, maximal activity, and duration of action. Conjugation of the insulin molecule with either zinc or protamine, or both, will convert the normally rapidly absorbed parenterally administered insulin to a preparation with a more prolonged duration of action. The various formulations of insulin are usually classified as short acting (0.5 to 14 h), intermediate acting (1 to 28 h), and long acting (4 to 36 h). The duration of action can vary, however, depending on injection volume, injection site, and blood flow at the site of administration. 

Although routine oral delivery of proteins has not been realized, some protein formulations have been developed for pulmonary delivery. Pulmonary delivery can result in either parenteral or local administration of the drug and, like oral delivery, is considered non-invasive. As with other routes of delivery, the size of the protein may limit its ability to be delivered systemi-cally via the pulmonary route of administration. Pulmozyme , a DNase-based formulation approved for the treatment of cystic fibrosis (CF), is delivered to the lungs by a nebulizer to clear blockage of the airways in the CF patient.Formulations for insulin to be administered by inhalation for systemic delivery of... 

In pharmaceutical preparations, soybean oil emulsions are primarily used as a fat source in total parenteral nutrition (TPN) regimens. Although other oils, such as peanut oil, have been used for this purpose, soybean oil is now preferred because it is associated with fewer adverse reactions. Emulsions containing soybean oil have also been used as vehicles for the oral and intravenous administration of drugs drug substances that have been incorporated into such emulsions include amphotericin, " diazepam, retinoids, vitamins, poorly water-soluble steroids, fluorocarbons, and insulin. In addition, soybean oil has been used in the formulation of many drug delivery systems such as liposomes, microspheres, dry emulsions, self-emulsifying systems, and nanoemulsions and nanocapsules. ... 

The cyclodextrins have obvious uses in parenteral formulations, including use as components of vehicles for peptides and other biologicals (ovine growth hormone, lL-2 and insulin)... 

The formulation of parenteral products involves careful consideration of the proposed route of administration and the volume of the injection. Injections are administered to the body by many routes into various layers of the skin, the subcutaneous and muscle tissue, into arteries or veins, into or around the spinal cord, or directly into various organs (e.g., the heart or the eye). The volume to be injected can range from microliters, typically diagnostic agents administered intradermally or insulin administered subcutaneously, to several liters administered intravenously as infusions. The route of administration and the volume to be injected affect the composition of the formulation. 

Directly from the beginning of the therapeutic use of proteins and peptides, parenteral formulations were of utmost importance, like sc formulations of insulin, for example. This was mainly triggered by special aspects from three different areas ... 

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