Glucose-containing formulations

In Fig. 23, the role of moisture in bimolecular reactions is classified by Hageman into three cases. The increases in reaction rate are attributed to a change in state of the water associated with the solid as reflected by a lower effective viscosity. In Case I, there is a continual increase in reaction rate with increasing water content above the monolayer. When all the reactant has been solubilized and further water dilutes the medium. Case II results. If the dilution is extensive, or if water is a product inhibitor of decomposition, a rate reduction can be observed (Case III). Case III behavior is an example of the effect of moisture on the progress of the Malliard reaction for the glucose-containing formulations of a-A-acetyl-L-lysine, poly-L-lysine, insulin, casein, and plasma proteins. " The fact that there can be a maximum degradation rate at a humidity other than 100% RH is observed in other situations as well. 

The presence of excipients in a formulation can influence product stability. The conceptually appealing strategy of including a moisture scavenger in a formulation is based on this. In glucose-containing systems, it was demonstrated that liquid and solid... 

As with most modeling efforts, the mathematical formulation is the easy part. Picking the right values from the literature or experiments is more work. An immediate task is to decide how to characterize the substrate and product concentrations. The balance equations for substrate and product apply to the carbon content. The glucose molecule contains 40% carbon by weight so S will be 0.4 times the glucose concentration, and 5q = 0.04. Similarly,... 

The incidence of diabetes and decreased glucose tolerance among the elderly is well documented [116,135-137]. Because of this, formulators should make every attempt to avoid using any sugar-containing excipients in their production processes. 

Perhaps the most important medical use of dialysis is in artificial kidney machines, where hemodialysis is used to cleanse the blood of patients whose kidneys have malfunctioned. Blood is diverted from the body and pumped through a cellophane dialysis tube suspended in a solution formulated to contain many of the same components as blood plasma. These substances—glucose, NaCl, NaHC03, and KC1—have the same concentrations in the dialysis solution as they do in blood, so that they have no net passage through the cellophane membrane. 

Nasal administration of formulations containing insulin plus 0.125% TDM concurrently at time 0 caused a rapid and significant increase in plasma insulin levels and a corresponding decrease in blood glucose levels (described above). When an interval of 2 h elapsed between TDM addition and insulin administration, a significant attenuation was noted in the maximal increase in plasma insulin, as well as in the maximal reduction in blood glucose levels [10]. The experimental protocol described above was then used to assess the amount of insulin absorbed when the interval between TDM administration and insulin administration was... 

Several peptide products used in the treatment of diabetes mellitus, in addition to insulin, are currently administered by subcutaneous injection and these drugs are candidates for development of nasal formulations. Glucagon-like peptide-1 (GLP-l)-related peptides stimulate the insulin response to glucose and diminish the release of glucagon after a meal. These effects diminish the excessive postprandial increase in glucose observed after a meal in persons with type 2 diabetes mellitus. GLP-1-related peptides must be administered by subcutaneous injection before meals in order to be effective. This requirement for injection before each meal is likely to impact the utilization of these products by persons with type 2 diabetes. Exendin-4 is a GLP-1-related peptide with a molecular mass of 4.2 kDa. The development of a GLP-1-related peptide nasal formulation containing an absorption enhancer would allow patients to scll-administer one of these drugs just before a meal without the need for a subcutaneous injection. 

Traditionally, the production of mAbs uses complex culture media containing glucose and amino acids as the main sources of carbon for cell metabolism, as well as vitamins, micronutrients and sometimes animal serum, usually fetal bovine serum. Chapter 5 provides a discussion on composition of culture media and recent trends in the search for formulas that do not require the use of animal serum, or of proteins of animal origin. These serum-free formulations use substitutes such as peptones, epithelial and fibroblast growth factors, hydrolysates, yeast extract, choline, and inositol. For the production of mAbs, various serum-free formulas are available, some of these developed specifically for a given cell line (Chu and Robinson, 2001). The development of those media is easier for non-anchorage-dependent cells, such as those used for mAb production. Thus, approximately 50% of the antibodies for therapeutic use are already produced using serum-free media. In some circumstances, the elimination of serum should be accompanied by the addition of other substances with the same shear stress protective effect of serum proteins,... 

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