Insulin formulations/preparations

The effect of processing technique on the aerosol performance of insulin formulations prepared by DG antisolvent precipitation and spray drying has been investigated. Two types of insulin formulations were produced. They were 1 20 insulin-mannitol (IM) and 1 20 8 insulin-mannitol-citric acid (IMC). Mannitol is an excipient commonly used to improve aerodynamic performance of powders for inhalation delivery. Citric acid has been found effective in improving insulin absorption in the lungs. ... 

Commercial insulin preparations differ in a number of ways, including differences in the recombinant DNA production techniques, amino acid sequence, concentration, solubility, and the time of onset and duration of their biologic action. In 2003, seventeen insulin formulations were available in the USA. 

Similar experiments were carried out using sucrose esters in nasal insulin formulations (Figure 7). It was observed that tetradecanoylsucrose and tridecanoylsucrose were more effective in stimulating insulin absorption as compared with decanoyl-sucrose and dodecanoylsucrose. But—compared with TDM at concentrations of 0.03%—the sucrose esters were less effective in promoting nasal absorption [66], Sucrose cocoate (SL-40) is produced by the chemical esterification of coconut oil with sucrose it has frequently been used in cosmetic and dental preparations as an excipient. When this excipient was formulated with insulin at 0.125,0.25, and 0.5% concentrations, the associated plasma levels of insulin increased rapidly whereas there was no enhancement of insulin plasma levels when insulin in saline was admin-... 

Since the concentrations of insulin to be administered in the sheep model would have been large, the insulin-loaded chitosan nanoparticles were not investigated in that model. However, the pharmacodynamics and pharmacokinetics of various insulin-chitosan preparations were compared with postloaded insulin-chitosan nanoparticles. It was found that chitosan solution and chitosan powder formulations were far better, with the chitosan powder formulation showing a bioavailability of 17% as against 1.3 and 3.6% for the chitosan nanoparticles and chitosan solution [72], The effects of the concentration and osmolarity of chitosan and the presence of absorption enhancers in the chitosan solution on the permeation of insulin across the rabbit nasal mucosa in vitro and in vivo were investigated, and the same... 

Insulin (molecular weight 7000) has been formulated in controlled release microbeads and pellets (135,136). A solvent evaporation micro-encapsulation procedure was used to produce microspheres with up to 20% by weight insulin. Solvent-casting techniques were used to prepare pellets. The investigations demonstrated that the PLA... 

Other Formulations. Neural networks have been applied to the modeling of pellet formulations to control the release of theophylline [63] and to control the rate of degradation of omeprazole [64]. They have also been applied to the preparation of acrylic microspheres [65] and to model the release of insulin from an implant [66]. In arecent study from Brazil, the release of hydrocortisone from a biodegradable matrix has been successfully modeled [67]. 

Insulin aggregation and precipitation was an impediment to the development of implantable devices for insulin delivery as noted by several investigators working with conventional insulin infusion devices [51-54]. The potential causes of the observed aggregation and precipitation are thermal effects, mechanical stress, the nature of the materials in contact with the insulin solution, formulation factors, and the purity of the insulin preparation. 

Insulin, whatever its source, may be formulated in a number of ways, generally in order to alter its pharmacokinetic profile. Fast (short)-acting insulins are those preparations that yield an elevated blood insulin concentration relatively quickly after their administration (which is usually by s.c. or, less commonly, by i.m. injection). Slow-acting insulins, on the other hand, enter the circulation... 

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. " ... 

Insulin has a half-life of only a few minutes when injected intravenously. It is therefore prepared in different formulations for subcutaneous injection, with different half-lives of absorption, giving different durations of action. The main formulations, with their approximate durations of action are given in Table 2. 

The new, short-acting insulins can be bound to protamine, allowing the preparation of mixed formulations. In an open, randomized, single-dose, three-way, crossover trial biphasic insulin aspart 30 (30% aspart plus 70% protaminated aspart, BIAsp 30), biphasic insulin lispro 25 (25% lispro plus 75% protaminated lispro, Mix 25), and biphasic human insulin 30 (30% regular plus 70% isophane insulin, BHI 30) were compared in 45 patients (15). Biphasic insulin aspart improved postprandial control better. There were 23 episodes of hypoglycemia with BIAsp 30, 19 with Mix 25, and 11 with BHI 30 two episodes with BIAsp 30, five with Mix 25, and two with BHI 30 required third-party intervention. 

The new short-acting insulins can be bound to protamine, allowing the preparation of mixed formulations. In a randomized, open, crossover study for 24 weeks, a 50% mixture of insulin lispro and protamine lispro injected... 

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. 

Insulin Insulin may be stable for 1 month if stored at a temperature of 25 °C, but care should be exercised not to expose it to heat or light. However, for better stability, storing at refrigerator temperature (2° to 8 °C) is recommended. Use of carrier proteins such as albumin can be formulated along with insulin preparations, since they adsorb to containers. 

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