Insulin solution preparation

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. 

A solution prepared by dissolving 20.0 mg of insulin in water and diluting to a volume of 5.00 mL gives an osmotic pressure of 12.5 mm Hg at 300 K. What is the molecular mass of insulin ... 

I-Tyr-A 14-insulin (e.g. human, porcine or bovine insulin) is prepared according to routine procedures. Aliquots in buffer solution (0.05 M phosphate buffer, pH 7.4,1 % BSA, 0.05 % NaN3) are lyophilized. 

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 Preparations. The various commercially available insulin preparations are listed in Table 2.5-7. Amorphous insulin was the first form made available for clinical use. Further purification afforded crystalline insulin, which is now commonly called "regular insulin." Insulin injection. USP. is made from zinc insulin cry.stals. For some time, regular insulin. solutions have been prepared at a pH of 2.8 to 3.S if the pH were increased above the acidic range, particles would be formed. More highly purified insulin, however, can be maintained in solution over a wider pH range, even when unbuffered. Neutral insulin solutions have... 

Microcrystals of proteins with mean diameter <3 pm can be prepared for sustained release by the seed zone method. The sustained release effect could be attributed to the decreased solubility of the microcrystals [12]. This method has been used in the making of insulin microcrystals of rhombohedra shape without aggregates. Following intratracheal instillation of the insulin microcrystal suspension (32U/kg) to rats, the blood glucose levels were reduced and hypogly-caemia was prolonged for 13 h when compared with the unmodified insulin solution [12]. 

Each week prepare a fresh solution of 1 19 insulin in matrix solution 25 fiL insulin solution is added to 475 /jlL matrix solution. 

Crude PNA Dilutions of 1 10, l.TOO, and 1 1000 of crude PNA in matrix-insulin solution are prepared by performing a series dilution of 1 fjL crude PNA into three consecutive portions of 9 /xL matrix-insulin solution. The MS sample plate is spotted with 1 jaL of each the 1 100 and 1 1000 dilutions, with the latter typically providing the best results. 

Insulin fibril formation is particularly important with the advent of infusion pumps to deliver insulin. In these devices, insulin is exposed to elevated temperatures, the presence of hydrophobic surfaces, and shear forces, all factors that increase insulin s tendency to aggregate. These problems can be overcome if the insulin is prepared with phosphate buffer or other additives. Another physical stability problem associated with insulin is adsorption to tubing and other surfaces. This normally occurs if the insulin concentration is less than 5 lU/mL (0.03 mM), and it can be prevented by adding albumin to the dosage form if a dilute insulin solution must be used (34). 

In the case of Msp A, microspheres were prepared in a mild environment that is, an organic solvent and a high shear were absent. A circular dichroism (CD) spectrum of insulin released from Msp A was virtually identical to that of a freshly prepared native insulin solution. This means that the released insulin preserved its secondary structure. In contrast, the CD spectrum for Msp B indicated a loss of secondary structure integrity due to both the use of dichloro-methane and the harsh preparation conditions employed (48). 

Insulin loaded nanocapsules dispersed in biocompatible microemulsion resulted in significantly greater reduction in blood glucose levels than aqueous insulin solution. This demonstrated that formulation of peptides within nanoc sules administered dispersed in microemulsion can facilitate oral absorption of encapsulated peptide. Such system can be prepared in situ by the interfacial polymerization of a w/o microemulsion. 

NPH and Lente insulins differ in their ability to form mixtures with neutral insulin solutions (Berger et a/., 1982 Heine eJ a/., 1984 Forlani et al, 1986 Brange et al., 1987). Both can be mixed with regular insulin immediately before injection. Mixtures of NPH with regular insulin preserve their pharmacokinetic characteristics over time. This is not the case with Lente/regular mixtures because the surplus of zinc ions in the Lente part will combine with part of the insulin in solution and change it into a Semilente-like preparation. 

Jet injectors deliver insulin transcutaneously by an air-jet mechanism. The insulin solution or suspension is forced at high pressure through a fine nozzle, penetrates the skin without a needle, and creates a multitude of small depots. The dispersion of insulin deposited in the tissue explains the more rapid absorption of both rapid- and retarded-acting preparations (Taylor et al, 1981 Malone eta/., 1986 Houtzagerse/a/., 1988). Jet injection seems to affect the action profile of NPH insulin more markedly than that of the Lente t e insulins (Houtzagers et al, 1988). These devices are not painless and, in a European study, not well accepted by patients irrespective of the presence or absence of needle phobia (Houtzagers etal, 1988). However, in a more recent American study, the majority of patients preferred to take insulin by jet injector compared to needle injection (Denne et al, 1992). Jet injection has been found to be associated with a diminished antibody... 

A colony of rabbits is prepared for the assay by determining for each rabbit that volume of insulin solution containing 2 units/ml, which when injected subcutaneously under the test conditions will cause a marked but non-convulsive fall in blood sugar level. This volume, which may be expressed in terms of body weight of the animal or as a fixed dose per animal, is referred to as the standard volume . As an alternative the same standard volume , suitably 0 3 to 0-5 ml, may be adopted for all rabbits, any abnormally sensitive or insensitive animals being discarded. 

Crystalline insulin, C45Hj90i4NxiS.3H20, has been obtained by various methods, including the addition of pyridine to insulin solutions at pH 5-6. The potency of the crystalline hormone is very little greater than that of some of the amorphous preparations, namely, 23-26 international units per mg. Chemically, insulin belongs to the peptides, which may explain its destruction in the alimentary tract, when given by the mouth. 

The PLGA-PEG-PLGA triblock copolymer was dissolved in the cold water at 5 °C to make a 23 wt% solutioa Insulin solutions were prepared in buffer (isotonic 10 mM PBS, pH 7.4) to a concentration of 5.04 mg/nil arui zinc was added (0.0, 0.2 wt%) to the hydrogel solutioa Then 2 ml of each formulation were placed in vials, incubated at 37 °C until forming gels, and 10 ml of PBS solution was added as a release medium. Release medium sarrqrles were withdrawn and replaced inunediately to keep the sink condition. Th were analyzed by reversed-phase high performance liquid chromatography (RP-... 

This is a crystalline product of insulin and an alkaline protein where the protein/insulin ratio is called the isophane ratio. This product gives a delayed and uniform insulin action with a reduction in the number of insulin doses necessary per day. Such a preparation may be made as follows 1.6 g of zinc-insulin crystals containing 0.4% of zinc are dissolved in 400 ml of water, with the aid of 25 ml of 0.1 N hydrochloric acid. To this are added aqueous solutions of 3 ml of tricresol, 7.6 g of sodium chloride, and sufficient sodium phosphate buffer that the final concentration is As molar and the pH is 6.9. 

Insulin is a hormone responsible for the regulation of glucose levels in the blood. An aqueous solution of insulin has an osmotic pressure of 2.5 mm Hg at 25°C. It is prepared by dissolving 0.100 g of insulin in enough water to make 125 mL of solution. What is the molar mass of insulin ... 

Concerning drug delivery, electrically erodible polymer gels for controlled release of drugs have been prepared, and a measured release rate of insulin has been observed under electrical stimulus [69]. A suspension of zinc insulin in a mixed solution of poly(ethyloxazoline) and PMAA was formed into a gel by decreasing the pH of the suspension. The obtained complex gel with 0.5 wt% of insulin was attached to a woven platinum wire cathode which was 1 cm away from the anode and immersed in 0.9% saline solution. When a stepped function of electrical current of 5 mA was applied to the insulin-loaded gel matrix, insulin was released in a stepwise manner up to a release of 70%. The insulin rate measured was 0.10 mg/h. 

Theory Insulin zinc suspension is nothing but a neutral suspension of insulin in the form of water insoluble complex with ZnCl2. Determination of both total zinc and zinc in solution is performed on a sample of the supernatant liquid obtained by centrifuging the suspension. The percentage of total zinc and of zinc in solution varies according to the strength of the preparation viz., 40, 80 or 100 units ml-1. 

Combination preparations contain insulin mixtures in solution and in suspension (e.g., ultralente) the plasma concentration-time curve represents the sum of the two components. 

The higher molecular mass contaminants in conventional insulin preparations include various proteases. Such preparations are generally maintained in solution at acidic pH values (often as low as pH 2.5-3.5). This minimizes the risk of proteolytic degradation of the insulin molecules, as contaminant proteases are inactive at such pH values. 

AAS is used in a number of limit tests for metallic impurities, e.g. magnesium and strontium in calcium acetate palladium in carbenicillin sodium and lead in bismuth subgallate. It is also used to assay metals in a number of other preparations zinc in zinc insulin suspension and tetracosactrin zinc injection copper and iron in ascorbic acid zinc in acetylcysteine lead in bismuthsubcarbonate silver in cisplatinum lead in oxyprenolol aluminium in albumin solution and calcium, magnesium, mercury and zinc in water used for diluting haemodialysis solutions. 

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