Stability of nicardipine hydrochloride in intravenous solutions.

The stability of nicardipine hydrochloride in large-volume i.v. solutions was studied. Admixtures of nicardipine hydrochloride 0.05 and 0.5 mg/mL were prepared in 5% dextrose and 0.45% sodium chloride injection, 5% dextrose and 0.9% sodium chloride injection, 0.45% sodium chloride injection, 0.9% sodium chloride injection, 5% dextrose and lactated Ringer's injection, 5% dextrose injection, lactated Ringer's injection, 5% sodium bicarbonate injection, and 5% dextrose injection with potassium chloride 40 meq/L. Two glass and two polyvinyl chloride (PVC) containers of each solution were prepared and stored at ambient room temperature under normal fluorescent light. Samples were removed and tested for nicardipine concentration by stability-indicating high-performance liquid chromatography at 0, 24, 48, and 72 hours and seven days. Testing included visual checking and optical density measurements. The admixtures remained clear and slightly yellow except for nicardipine hydrochloride in sodium bicarbonate injection, which showed immediate precipitation, and nicardipine hydrochloride in lactated Ringer's injection, which increased in optical density at 400 nm over time. There were no significant changes in nicardipine concentrations in nicardipine concentrations in glass containers. Admixtures stored in PVC containers showed a slow, constant decline in nicardipine concentrations, sometimes to less than 85% of the initial drug concentration within 24 hours, except for nicardipine hydrochloride in lactated Ringer's injection or 5% dextrose and lactated Ringer's injection, which showed an immediate and continuing rapid loss. Nicardipine hydrochloride 0.5 and 0.05 mg/mL in eight i.v. solutions was stable in glass containers for up to seven days. Drug concentrations slowly decreased in PVC containers. The drug was not stable in 5% sodium bicarbonate injection or in PVC bags containing lactated Ringer's injection or 5% dextrose and lactated Ringer's injection.

Stability of esmolol hydrochloride in intravenous solutions.

The stability of esmolol hydrochloride in a variety of i.v. solutions was studied. Solutions of esmolol hydrochloride 10 mg/mL were prepared separately in 0.45% sodium chloride injection, 0.9% sodium chloride injection, 5% dextrose injection, 5% dextrose and 0.45% sodium chloride injection, 5% dextrose and 0.9% sodium chloride injection, 5% dextrose with lactated Ringer's injection, lactated Ringer's injection, 5% sodium bicarbonate injection, and 5% dextrose injection with potassium chloride 40 meq/L. One glass and one polyvinyl chloride container of each solution (except glass only in the case of the solution in 5% sodium bicarbonate injection) were stored in the dark at 5 degrees C, under ambient room light at 23-27 degrees C, in the dark at 40 degrees C, and under intense light at 25-30 degrees C. At storage intervals up to 168 hours, samples were tested for esmolol hydrochloride concentration by high-performance liquid chromatography. Optical density and pH were also measured. Esmolol hydrochloride was stable in the various i.v. fluids for at least 168 hours when stored at 5 degrees C or 23-27 degrees C, for at least 24 hours when stored under intense light, and, with one exception, for at least 48 hours when stored at 40 degrees C. When mixed with 5% sodium bicarbonate injection, the drug was stable for only about 24 hours at 40 degrees C. There were no substantial changes in optical density or pH. The type of container had no effect on stability. With one exception, esmolol hydrochloride was stable in all the i.v. solutions under all the conditions tested.

Effects of intravenous pentafraction on lung and soft tissue liquid exchange in hypoproteinemic sheep.

Effects of infusing pentafraction (Pen), a synthetic hydroxyethyl starch plasma volume expander, on lung and soft tissue lymph flux were compared in nonanesthetized sheep that were protein depleted by batch plasmapheresis. Pen (5%) was infused to raise pulmonary arterial wedge pressure by 5 mmHg for 2 h (1.8 +/- 0.3 l). Pen raised plasma osmotic pressure from plasmapheresis baseline (10.7 +/- 2.2 mmHg; preplasmapheresis baseline, 19.6 +/- 0.6 mmHg) to 16.6 +/- 2.4 mmHg. After Pen, lung lymph flows peaked at 3.9 +/- 2.0 times a preplasmapheresis baseline value of 1.0 (plasmapheresis baseline, 2.7 +/- 0.7), but soft tissue lymph flows rose insignificantly. Plasma Pen concentrations were 2.3 +/- 1.0% postinfusion and 1.6 +/- 0.3% at 12 h. Pen mean molecular masses at these times, measured by high-performance liquid chromatography, were 160 +/- 44 and 129 +/- 23 kDa, respectively. In lung lymph, Pen concentrations were 0.8 +/- 0.6% postinfusion and 0.7 +/- 0.2% at 12 h, with mean molecular masses of 125 +/- 44 and 112 +/- 18 kDa, respectively. In soft tissue lymph Pen was nearly undetectable postinfusion, but at 12 h concentrations averaged 0.3 +/- 0.2% with a mean molecular mass of 80 +/- 10 kDa. The osmotic effectiveness of Pen may be related to its molecular mass, which was large enough to restrict filtration so that the plasma-to-lung lymph osmotic pressure gradient widened. Pen remained effective in the circulation for at least 24 h.

Stability of esmolol hydrochloride and sodium nitroprusside in intravenous admixtures.

The stability of esmolol hydrochloride and sodium nitroprusside in an admixture containing both drugs was studied. Solutions containing sodium nitroprusside in a final concentration of approximately 200 micrograms/mL and esmolol hydrochloride in a final concentration of 10 mg/mL in 5% dextrose injection were prepared in a 250-mL volumetric flask. The flask was wrapped with a light-protective cover, stored at ambient room temperature (15-30 degrees C), and protected from light. All experiments were conducted in triplicate with samples taken at 0, 2, 4, 8, and 24 hours. Testing included measurement of pH and absorbance at 400 and 600 nm. High-performance liquid chromatography was used to measure esmolol hydrochloride and sodium nitroprusside concentrations. No changes were observed in the physical appearance, pH, or absorbance of the admixtures. Neither the esmolol hydrochloride nor the sodium nitroprusside concentrations varied by more than 4% during the study. Under the conditions studied, esmolol hydrochloride is compatible with sodium nitroprusside in an admixture containing both drugs.

Compatibility of esmolol hydrochloride with morphine sulfate and fentanyl citrate during simulated Y-site administration.

The compatibility and stability of esmolol hydrochloride in admixtures during simulated Y-site injection of morphine sulfate or fentanyl citrate was studied. One milliliter of either morphine sulfate (15 mg/mL) or fentanyl citrate (0.05 mg/mL) was injected into a running infusion of esmolol hydrochloride (10 mg/mL) in 5% dextrose and 0.9% sodium chloride injection, and the solution was visually observed for changes. To determine the stability of the drugs during Y-site injection, esmolol hydrochloride 4 mL (1000 mg) in 5% dextrose and 0.9% sodium chloride injection was combined with 100 mL of either morphine sulfate 15 mg/mL or fentanyl citrate 0.05 mg/mL to simulate concentrations of the drugs that might be expected during Y-site injection. The admixtures were stored at ambient room temperature under normal light, and drug concentrations were determined using high-performance liquid chromatography at time zero and at two, four, and eight hours. Admixtures were also tested for pH and observed for visual changes. No immediate changes were observed in any of the admixtures, and the concentrations of the drugs varied by less than 4% throughout the study period. No precipitate or color changes were noted during Y-site injection of either drug into the running esmolol infusion. Under all of the conditions studied, esmolol hydrochloride in 5% dextrose and 0.9% sodium chloride injection is compatible with morphine sulfate or fentanyl citrate.

High-performance liquid chromatographic method for the determination of esmolol hydrochloride.

A rapid high-performance liquid chromatographic method for the determination of esmolol hydrochloride, a new ultra-short-acting beta blocker, is described. The stability-indicating nature of the method was demonstrated by resolving esmolol from synthetic intermediates, potential impurities, and the product of decomposition. Reverse-phase liquid chromatography was performed with a microparticulate (10-micron) cyano-bonded silica-packed column, a fixed-wavelength UV absorbance detector (lambda = 280 nm), and a mobile phase of acetonitrile-0.005 M sodium acetate-acetic acid (15:84:1) pumped at 2 mL/min. The internal standard was 2-p-chlorophenyl-2-methylpropanol. A percent RSD of less than 1.7% and an accuracy (100% - mean error) of greater than 98.6% were achieved over the concentration range studied (100-500 micrograms/mL), with correlation coefficients greater than 0.9996.

Stability of nitroglycerin solutions in polyolefin and glass containers.

The stability of nitroglycerin in concentrations of 200 and 400 micrograms/ml in eight common intravenous solutions was studied. Two containers of each solution at each concentration, one glass and one polyolefin, were stored under each of the following conditions: intense light (1400-2000 foot-candles) and ambient room temperature (18-27 degrees C), normal light and ambient room temperature, dark and 40 degrees C, and dark and 5 degrees C. All samples were tested at 0 and 24 hours. Room temperature and refrigerated samples were also tested at 48 hours, 7 days, and 1 month. Testing included measurement for optical density at 400 and 600 nm, pH, and nitroglycerin content as determined by HPLC. The admixtures remained clear and colorless, and no appreciable changes in pH were observed. HPLC assays showed no significant changes in nitroglycerin concentrations. There were no differences in the stability of the admixtures stored in the glass and polyolefin containers. Nitroglycerin is compatible with each of the common intravenous solutions tested under the storage conditions and in the containers used for this study.

Pharmaceutical considerations of nitroglycerin.

During the past few years, there have been rapid changes in the pharmaceutical uses of nitroglycerin. New dosage forms and new delivery systems have become available, which have resulted in potential confusion to all concerned with the proper use of these systems. The goal of this review is to prevent confusion and to bring all the relevant information together. The various analytical techniques available for quality control of the dosage forms and for the study of the pharmacokinetics are reviewed, with the intent of enabling the reader to identify pertinent references rapidly. The interaction of nitroglycerin with packaging and plastic delivery devices is also reviewed so that the reader can make informed choices. Finally, the clinical pharmacy and pharmacokinetics are reviewed so as to bring the reader up to date in that area. After reading this article, the areas of nitroglycerin research that still need to be explored should be apparent.

High-performance liquid chromatographic assay for partially nitrated glycerins in nitroglycerin.

A high-performance liquid chromatographic method for determining the concentration of mononitroglycerins and dinitroglycerins in the commonly used pharmaceutical raw material nitroglycerin (10% w/w) on lactose USP is presented. A coefficient of variation of less than 5% for the partially nitrated glycerins was achieved over the range examined (0-4.0 micrograms/mg). Thirteen lots of raw material were examined and found to contain a total of less than 0.13% w/w partially nitrated glycerins. A variable wavelength detector (lambda = 218 nm) and a microphenyl column were employed. The mobile phase was acetonitrile-water (36:64) pumped at 2 ml/min. The internal standard was isosorbide dinitrate. Total analysis time was 12 min.

High-performance liquid chromatographic determination of sodium nitroprusside.

A rapid high-performance liquid chromatographic method for the determination of nitroprusside in commercial lyophilized products or in intravenous admixture solutions is described. The method is stability-indicating. Reversed-phase liquid chromatography was performed using a microparticulate (10 micrometer) phenyl column with a mobile phase acetonitrile--phosphate/tetrabutylammonium hydroxide buffer (pH 7.1) (30:70) and detection at 210 nm. A coefficient of variation of less than 3.1% was achieved over the concentration range studied (10--50 microgram/ml). Total analysis time was 9 min. This method was used to show that there is a small loss of nitroprusside due to photodegradation during intravenous infusion, even when the admixture container is wrapped in foil as recommended and used expeditiously.

Loss of nitroglycerin from solutions to intravenous plastic containers: a theoretical treatment.

The physical instability of nitroglycerin solutions in plastic containers has been reported extensively. A systematic study of potency loss in plastic infusion bags were reported recently. This paper presents a theoretical treatment of the data and a proposed model consisting of adsorption onto the surface followed by partitioning into the plastic.

Evaluation of sustained-action chlorpheniramine-pseudoephedrine dosage form in humans.

This investigation compared the bioavailability of chlorpheniramine and pseudoephedrine from a sustained-action capsule and a combination of two reference standard tablets in 24 normal human subjects. The capsule contained 8 mg of chlorpheniramine maleate and 120 mg of pseudoephedrine hydrochloride, and the tablets each contained half of the amount of the chlorpheniramine or pseudoephedrine in the capsule. Because the capsule was a combination product, a new study design had to be developed to accommodate steady-state conditions for both drugs. Each subject received the capsule (every 12 hr) and the combination of the reference tablets (every 6 hr) for 8 days according to a two-way crossover design. Serial blood and urine samples were taken during the entire study. Plasma and urine samples were assayed for chlorpheniramine and pseudoephedrine by sensitive and specific high-pressure liquid chromatographic or GLC methods. There were no significant differences in the plasma concentration profiles of chlorpheniramine and pseudoephedrine at all times, except when the capsule developed peaks or the tablets developed nadirs. The highest mean peak plasma concentrations for the capsule and the tablets were 38.7 and 32.9 ng of chlorpheniramine/,ml and 525 and 515 ng of pseudoephedrine/ml, respectively. The mean biological half-lives of chlorpheniramine and pseudoephedrine were 21.6 and 8.0 hr, respectively. The AUC and unchanged drug excreted in urine, after a single dose and at steady state, showed that the sustained-action capsule (given every 12 hr) and the reference standard tablets (given every 6 hr) were bioequivalent.

Bretylium tosylate intravenous admixture compatibility. I: Stability in common large-volume parenteral solutions.

The stability of bretylium tosylate in 11 common large-volume parenteral solutions was studied. Two containers of each solution, one glass and one plastic (except for mannitol and sodium bicarbonate solutions, which were available in glass only), were stored at each of the following conditions: intense light (1400-2000 foot candles), ambient room temperature with normal light, 40 degrees C, and 4 degrees C. All samples were tested at 0 and 24 hours; some samples were also tested at 48 hours and 7 days. Testing included measurement for optical density at 4000 and 600 nm, pH level, and bretylium content as determined by HPLC. The admixtures remained clear and colorless, except that mannitol precipitated out of mannitol solutions stored at 4 degrees C. No appreciable changes in pH were observed. HPLC assays showed no significant changes in bretylium tosylate concentrations. Bretylium tosylate is compatible with each of the 11 common intravenous solutions chosen for investigation under the storage conditions studied. Admixtures with mannitol should not be refrigerated, because mannitol crystallizes from solution at refrigerator temperatures.