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Biomedical subjects

S H Yalkowsky

Publications and source records attributed to S H Yalkowsky.

122 records · Page 7Linked to original sources
PubMedDate not supplied

Studies in phlebitis. IV: Injection rate and amiodarone-induced phlebitis.

Using a rabbit ear model and techniques developed previously (1) the relationship between injection rate and injection phlebitis is investigated for amiodarone HCl and its vehicle. A number of injection rates ranging from 0.02 to 3.0 ml/min are studied using this model. Thermal measurements and visual evaluations are used for phlebitis quantitation. The severity of phlebitis is found to be dependent upon the injection rate for amiodarone HCl while the vehicle did not produce phlebitis at any rate. Strong correlations between the thermal measurements and visual evaluations are found for both amiodarone HCl and its vehicle.

Amiodarone↗
PubMedDate not supplied

Lysis of human red blood cells 1: Effect of contact time on water induced hemolysis.

A dynamic in vitro method for the determination of the degree of hemolysis induced by parenteral formulations is presented. This method utilizes a dual syringe pump apparatus that enables the mixing of a formulation with blood in various ratios and for various contact times. Formulations with varying tonicity were used to test the method. Hemolysis is shown to be directly related to both the hypotonicity of the test solution and the contact time. The proposed method makes it possible to evaluate the hemolytic effects of parenteral formulations at physiologically realistic contact times and formulation:blood ratios.

Erythrocytes↗
PubMedDate not supplied

Studies in phlebitis VIII: evaluations of pH solubilized intravenous dexverapamil formulations.

Injectable and infusion formulations of dexverapamil are evaluated for their potential to produce phlebitis. The evaluation technique utilizes two independent in vitro methods and two in vivo methods to screen a pH solubilized drug for its potential to induce phlebitis due to precipitation at the injection site. One method is based upon a theoretical calculation that simulates the change of solubility upon dilution. Its predictions are confirmed by the second method which consists of an in vitro precipitation experiment. Thermal and visual evaluations are then obtained from an in vivo rabbit ear injection. Dexverapamil formulations that have low buffering capacity are shown to contribute to the incidence of phlebitis to a greater extent than the properly buffered formulations. The calculation and the in vitro precipitation experiment are found to be useful in formulating pH solubilized parenterals. They enable the formulator to optimize pH, drug concentration, and buffer concentration without the need for animal studies. The results of this study show the importance of selecting a buffer that provides adequate buffer capacity in the formulations.

Animals↗
PubMedDate not supplied

Parenteral formulation of Flavopiridol (NSC-649890).

Flavopiridol [5,7-dihydroxy-8-(4-N-methyl-2-hydroxypyridyl)-6' -chloroflavone hydrochloride] is a flavonoid with weak electrolyte properties and an intrinsic aqueous solubility of 0.024 mg/mL. Neither cosolvency complexation, nor pH control alone can produce an acceptable 10 mg/mL formulation that will not precipitate when diluted with blood. However, a combination of buffer and cyclodextrin or buffer and cosolvent can produce an acceptable 10 mg/mL formulation. In this paper, Flavopiridol is shown to be stable for at least one year in 30% hydroxypropyl beta-cyclodextrin/0.1 M citrate buffer (4.52). This formulation does not precipitate for at least one hour upon dilution with Sorensen's phosphate buffer pH 7.4.

Buffers↗
PubMedDate not supplied

Solubilization of diazepam.

Several attempts to increase diazepam solubility are in the literature. This study discusses these different solubilization approaches. Specific reference is given to the rationale in the application of pH control, cosolvency, surfactants, and cyclodextrins. It was found than cosolvency is a more attractive means of solubilizing diazepam than either pH control, surfactants, or cyclodextrins. Advantages, assumptions, and limitations of these diazepam solubilization techniques are also described.

Anti-Anxiety Agents↗
PubMedDate not supplied

Lysis of human red blood cells. 3: Effect of contact time on surfactant-induced hemolysis.

The percent hemolysis induced by various surfactants was determined as a function of the formulation composition and formulation: blood contact time using the dynamic in vitro method of Krzyzaniak et al. (1). The amount of hemolysis induced by nonionic surfactant formulations is shown to be relatively low and to increase only slightly with contact time. However, when ionic surfactant formulations are used, hemolysis is shown to increase dramatically with surfactant concentration and to be sigmoidally related to the logarithm of contact time. Since surfactant-induced hemolysis is dependent on both the surfactant concentration and the contact time, intravascular hemolysis must be evaluated using an in vitro method that simulates the intravenous injection site. With this information, hemolytically safe surfactant formulations can be developed for intravenous administration.

Erythrocytes↗