Comparison of the physicochemical properties of branded and generic glucose-added maintenance hypotonic infusion fluids to assess the potential for phlebitis and incompatibility with other drugs.

In Japan, the switch from branded to generic infusion fluids has been promoted as a national policy. Recently, as generic products have been in short supply, the switch from generic to branded infusion fluids has increased. However, certain additives for injectable infusion fluids, such as nonvolatile acids like acetic acid and hydrochloric acid, are not required to be listed in the package insert. We hypothesized that the addition of nonvolatile acids may be one of the reasons for the differences in physicochemical properties between the branded and generic infusion fluids. We have previously reported that in other types of electrolyte infusion fluids, a variation in pH can cause incompatibility with other drugs, and variation in titratable acidity and osmolality can lead to phlebitis. Glucose-added maintenance hypotonic infusion fluid (listed as type-3G) is commonly used as a maintenance solution when energy support is needed. However, nonvolatile acid is added to prevent the caramelization of glucose, resulting in higher osmolality and titratable acidity and lower pH. Therefore, we hypothesized that both phlebitis and incompatibility with other drugs are likely to occur; hence, we measured and evaluated the physicochemical properties of branded and generic type-3G infusion fluids. We show that the osmolality, pH, and titratable acidity of all evaluated branded and generic products differed significantly and that these properties should be evaluated together to avoid phlebitis and incompatibility with other drugs when switching between branded and generic type-3G infusion fluids.

Physicochemical Properties of Branded and Generic Infusion Fluid Preparations: Results of a Comparative Experimental Study on Type 2 Hypotonic Infusion Fluid.

In Japan, four different types of hypotonic infusion fluids, namely, types 1-4, are available and used depending on the patient's condition. Although branded and generic products for each type of hypotonic infusion fluid are available, their physicochemical properties are unknown. For types 1 and 3 fluids, differences in the physicochemical properties of branded and generic products lead to different adverse events when administered. In the present study, we measured titration acidity, pH, and osmolality of branded and generic type 2 hypotonic infusion fluids, which have recently been recognized as useful for maintenance infusion among pediatric patients. We herein assessed their physicochemical information required while selecting a product in clinical practice. Experiments were performed using one branded and two generic products of type 2 hypotonic infusion fluids. Titration acidity was measured via neutralization titration, osmolality was measured via freezing point depression, and pH was measured via potentiometry using a glass electrode. Significant differences in titration acidity, which is a risk factor for metabolic acidosis, and pH, which is a risk factor for pH-dependent changes upon mixing, were observed between the branded and generic products. Our study indicates that titration acidity and pH should be evaluated appropriately to avoid adverse events in clinical practice while selecting a product of type 2 hypotonic infusion fluids. Our findings highlight the importance of evaluating the differences between branded and generic products, specifically when selecting it for pediatric patients with incompletely developed renal function and patients with impaired renal function.

Physicochemical properties of brand and generic infusion fluid preparations (Part 3): Investigation of type 1 hypotonic infusion fluids.

In Japan, the increasing use of generic drugs has led to a reduction in drug prices, which affect the steady supply of drugs. A "basic drug" system was introduced to rescue these drugs by eliminating gaps in drug prices among preparations with the same constituents. "Type 1" hypotonic infusion fluids, which are potassium-free and commonly used to treat dehydration, meet the definition of a "basic drug" in Japan, and there are no drug price gaps. However, there is a lack of information on the physicochemical properties of "type 1" hypotonic infusion fluids, making it difficult to identify differences among them. Extracellular fluid-replacement solutions and "type 3" hypotonic infusion fluids have different pH and titratable acidity. Here, we measured the pH, titratable acidity, and osmolality of six different "type 1" hypotonic infusion fluids and compared the results with respect to risk avoidance considering metabolic acidosis, changes upon mixing, and vascular pain. There was a significant difference, or trend toward significance, in titratable acidity, which is a risk factor for metabolic acidosis in patients with impaired renal function, and pH, which is a risk factor for change upon mixing, among all combinations except one of the infusion fluids. Thus, the selection of "type 1" hypotonic infusion fluids for children with immature renal function, elderly patients with impaired renal function, and patients with unknown pathophysiology, considering titratable acidity and pH, is an effective strategy for risk avoidance.