Physico-Chemical Properties and Local Toxic Effects of Injectables

Lysis of Human Red Blood Cells. 4. Comparison of in Vitro and in Vivo Hemolysis Data

“…This usefulness is shown in a study by Oshida et al 10 who evaluated the hemolytic potential and muscle damaging effects of many parenteral formulations. Hemolysis was determined by an in vitro method with a formulation: blood ratio of 10 and a contact time of 30 min.…”

“…[8][9][10][11][12][13][14][15][16] It is clear that most of these methods use a large formulation:blood ratio and long contact time to evaluate hemolysis. It has previously been determined that hemolysis increases with both the formulation:blood ratio 12,17 and contact time, [16][17][18][19][20] so the degree of hemolysis determined by these methods will be larger than the amount occurring following an iv injection.…”

Polar Solvents Decrease the Viscosity of High Concentration IgG1 Solutions Through Hydrophobic Solvation and Interaction: Formulation and Biocompatibility Considerations

“…A study by Oshida et al 16 showed a correlation between the hemolytic potential of injectable products and the development of muscle lesions with an increase in hemolytic potential related to the severity of muscle lesions. 16 Parenteral formulations that were determined to be nonhemolytic showed little or no change in muscle tissue. However, there was severe muscle damage in cases where the formulations were considered hemolytic.…”

“…Similarly, some polar solvents, including DMSO and DMA, are currently used in marketed products. [16][17][18] However, the only polar solvents previously used in marketed injectable products are DMSO and DMA. Therefore, we limited our studies to these two polar solvents for potential indications requiring subcutaneous injections and ultrahigh protein concentrations.…”

In Vitro and In Vivo Evaluation of a Novel Water-Soluble N-Glycyl Prodrug (N-GLY-CBZ) of Carbamazepine

“…13 For IV administration, various formulation strategies have been investigated, but many suffer from the risk of severe allergic reaction and formulation related toxicities. [14][15][16][17][18][19] A water-soluble prodrug that could be administered intravenously in a safe and effective formulation would be of considerable benefit. In addition, a prodrug with improved solubility characteristics could give rise to faster, less erratic, and more complete oral absorption with overall better bioavailability.…”