Assessment of the Physicochemical Stability of All‐in‐One Parenteral Emulsions for Neonates According to USP Specifications

Background: The purpose of this study was to describe the methodology to assess the stability of all‐in‐one (AIO) parenteral nutrition admixtures, containing glucose, proteins, and lipids, to the standards of U.S. Pharmacopoeia (USP <729>). The influence of calcium and commercially available lipid emulsions and amino acid solutions were also examined. Methods: Four batches of 5 AIO admixtures containing calcium were compounded with commercially available lipid emulsions and amino acid solutions. Two of them contained calcium. Their stability was tested under conditions simulating clinical use. All the admixtures were assessed for criteria set by the USP <729>: (1) mean droplet diameter (MDD) and (2) percentage of volume weighted particles with diameter > 5 μm (PFAT₅). Results: All admixtures were within the specifications set by the USP with respect to the MDD at 0, 24, and 48 hours, but only those batches lacking calcium met the benchmarks set by the pharmacopoeia, with respect to PFAT₅, on the day of preparation. Conclusions: The presence of calcium destabilized the admixtures, while the use of different commercial ingredients altered the admixtures’ characteristics. Only 1 batch of the AIO admixtures studied was found to be compliant with USP <729> standards.     

Evaluation of two prediction models for digoxin dosing

The relationship between the digoxin elimination parameter (A%) and creatinine clearance (CL_Cr) was determined, from blood level data of 160 hospital patients receiving digoxin tablets. The linear regression equation obtained, which varied only slightly from that reported by Jelliffe previously, was used to predict serum digoxin concentrations in 140 patients of four age groups (50–60, 60–70, 70–80 and 80–90 years). The predictions made were found to be less biased and more precise, irrespective of the age of the patients, than those produced using another predictive method known as Dobbs method. However, correlation coefficients of predicted versus measured serum digoxin concentrations for each method did not differ significantly and frequency distribution analyses of prediction errors gave poor results (up to 63% only). Therefore, neither method can be considered to be superior to the other nor can they be said to ensure accurate predictions of serum digoxin concentrations.     

The effect of food on the movement of pellets in the gastro-intestinal tract

The effect of food on the movement of pellets in the gastro-intestinal tract was investigated in seven volunteers, either by means of X-rays taken after oral administration of barium sulfate pellets or by means of saliva concentration profiles of lithium obtained after oral administration of lithium sulfate controlled-release pellets. The X-ray studies showed that food had an effect on the time required for the pellets to leave the stomach and on their degree of dispersion in the small intestine, but not on other parameters. The studies with the lithium sulfate controlled-release pellets showed that food had a significant effect only in one in three subjects.     

Evaluation of the percutaneous absorption and metabolism of some aminopropiophenones

The absorption of diethylpropion (DEP I), dimethylpropion (DMP I) and some of their basic metabolites into and passage through the skin was investigated and a comparison of their metabolism following oral and percutaneous administration made. High percentages (60-80%) of DEP I and its metabolites and a small percentage of DMP I and its metabolites were taken up into the skin in less than 2 min--the remaining percentages of the compounds were absorbed into the skin by a first order process. The rate of appearance of the compounds in the blood, which reflects their rate of passage through the skin, did not correlated with their rate of absorption into the skin. More metabolism occurred with all the compounds after their oral administration than after their percutaneous application.     

Evaluation of two prediction models for digoxin dosing

The relationship between the digoxin elimination parameter (A%) and creatinine clearance (CL_Cr) was determined, from blood level data of 160 hospital patients receiving digoxin tablets. The linear regression equation obtained, which varied only slightly from that reported by Jelliffe previously, was used to predict serum digoxin concentrations in 140 patients of four age groups (50–60, 60–70, 70–80 and 80–90 years). The predictions made were found to be less biased and more precise, irrespective of the age of the patients, than those produced using another predictive method known as Dobbs method. However, correlation coefficients of predicted versus measured serum digoxin concentrations for each method did not differ significantly and frequency distribution analyses of prediction errors gave poor results (up to 63% only). Therefore, neither method can be considered to be superior to the other nor can they be said to ensure accurate predictions of serum digoxin concentrations.