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David F Driscoll

Publications and source records attributed to David F Driscoll.

15 recordsLinked to original sources
PubMed2006

Establishing a stability window for medium- and long-chain-triglyceride lipid-based total nutrient admixtures using USP standards.

PURPOSE: The stability window of medium-chain triglyceride (MCT) and long-chain-triglyceride (LCT) lipid-based total nutrient admixtures (TNAs) was studied. METHODS: Sixteen different admixtures were selected for study. Of these, eight base macronutrient concentrations representing low and high concentrations were selected, along with low and high concentrations of electrolytes. All TNAs studied contained 2 mg of elemental iron as part of the trace-element formulation, an amount previously shown to produce unstable TNAs with pure LCT-based lipid injectable emulsions. All admixtures were prepared in triplicate and analyzed over five time intervals: time 1 (immediately after preparation), time 2 (after four days of storage at 6 +/- 2 degrees C), and times 3, 4, and 5, corresponding to 6, 24, and 30 hours of storage at 25 +/- 2 degrees C, respectively, after time 2. Stability was measured by comparing results with USP standards for fat globule size in lipid injectable emulsions. RESULTS: A total of 48 admixtures were studied. Samples at each time interval showed an inconsistent but general increase in the number of globules with a diameter of >1.8 microm over time. All admixtures met both the proposed pharmacopoeial criteria for stability with respect to mean droplet size and volume-weighted proportion of fat globules with a diameter of >5 microm. CONCLUSION: A wide range of macronutrients and micronutrients were tested in a series of MCT-LCT-based TNAs and found to be stable. The use of MCTs and LCTs in lipid injectable emulsions confers greater stability to TNAs than has been achieved with pure LCT-based formulations.

Drug Compounding↗
PubMed2006

Lipid injectable emulsions: Pharmacopeial and safety issues.

Lipid injectable emulsions have been routinely used in patients worldwide for over 40 years as a nutritional supplement in patients requiring parenteral nutrition. They can be given as a separate infusion or added into total parenteral nutrition admixtures. Despite such broad use, no pharmacopeial standards exist with respect to the optimal pharmaceutical characteristics of the formulation. Several attempts to establish standard physical and chemical attributes have been attempted by various pharmacopeias around the world, but without success largely due to technical issues regarding the creation of globule size limits. Recently, the United States Pharmacopeia has revised its previous efforts and developed two methods and criteria (under Chapter <729>) to measure the mean droplet size (Method I), and the large-diameter tail > 5 mum (Method II) of the globule size distribution to verify the stability of lipid injectable emulsions. Importantly, it is the latter size limits of Method II that have the greatest implications for infusion safety. The major safety issues involving lipid injectable emulsions include impairments in plasma clearance in susceptible patients, and the infusion of an unstable emulsion containing large quantities of potentially embolic fat globules. Recent animal studies investigating the toxicity from the infusion of unstable lipid injectable emulsions have shown evidence of oxidative stress and tissue damage to the liver when recommended globule size limits determined by Method II of the USP are exceeded. Adoption of Chapter <729> of the USP seems appropriate at this time.

Animals↗
PubMed2006

Pathological consequences to reticuloendothelial system organs following infusion of unstable all-in-one mixtures in rats.

BACKGROUND: Recent evidence of lung injury from the infusion of unstable lipid injectable emulsions as all-in-one mixtures (AIOs) was shown in a guinea pig infusion model. METHODS: We extended this research to a Sprague-Dawley rat infusion model, focusing our analyses on the dose of large-diameter fat globules (expressed as the volume-weighted percent of fat larger than 5 or 10 microm, PFAT5 or PFAT10) from the dispersed phase of emulsion mixtures of varying levels of stability, and the potential injurious effects on major tissues of the reticuloendothelial system (i.e., lungs and liver). RESULTS: Two identical infusion experiments (n=13 rats/study), involving stable (s-AIO) vs. unstable (u-AIO) mixtures were separately conducted, and differed in two respects: (1) duration of AIO infusion (24 h vs. 72 h) and, (2) starting PFAT5 levels for the u-AIO (24- vs. 72-h PFAT5: 0.682+/-0.055% vs. 0.117+/-0.024%, respectively). In both experiments, s-AIOs vs. u-AIOs were infused, and evidence of hepatic oxidative stress was noted by significantly higher tissue concentrations of malondialdehyde (MDA) during infusion of u-AIOs. The higher concentrations of MDA in the livers of animals receiving the u-AIOs were also accompanied by significantly higher plasma concentrations of AST in both infusion experiments suggesting injury. Levels of cytokines (IL-1beta, TNFalpha) in the lungs and livers in both infusion studies were variable. CONCLUSIONS: These results demonstrate the infusion of u-AIOs with starting PFAT5 levels of approximately 0.1% show evidence of pathological consequences to the liver and lungs, and therefore, such unstable AIO mixtures should probably be avoided in the clinical setting.

Animals↗
PubMed2006

Physicochemical stability of highly concentrated total nutrient admixtures for fluid-restricted patients.

PURPOSE: The physicochemical stability of highly concentrated total nutrient admixtures (TNAs) for fluid-restricted patients was studied. METHODS: Five TNAs made from lipid injectable emulsions (50:50 mixture of medium-chain and long-chain triglycerides) designed to meet the full nutritional needs of adults with body weights of 40-80 kg were chosen. Protein was included in the TNAs at 1.5 g/kg for each body weight and was supplied from a concentrated 16% mixture containing the essential and non-essential amino acids. All admixtures were contained in ethylene vinyl acetate bags and were aseptically prepared. Triplicate preparations of each TNA were investigated over 30 hours at room temperature by dynamic light scattering (DLS) and light extinction with single-particle optical sensing (LE-SPOS). RESULTS: No significant changes in the physicochemical stability of the TNAs were observed by DLS (mean droplet size) or LE-SPOS (large-diameter tail) from time 0 (immediately after compounding) to 30 hours. All TNAs met the mean-droplet-size criteria outlined by USP for 20% lipid injectable emulsions. CONCLUSION: Concentrated TNA formulations made from lipid injectable emulsions were stable for 30 hours at room temperature.

Humans↗
PubMed2006

Lipid injectable emulsions: 2006.

Lipid injectable emulsions are an essential source of fatty acids, as well as a daily source of calories. They have been used in the clinical setting for almost 40 years, but despite this, there are no established official standards governing pharmaceutical quality. After 15 years of development, the United States Pharmacopeia (USP), which writes such standards for all FDA-approved pharmaceuticals, is poised to adopt an official monograph for lipid injectable emulsions that sets pharmaceutical requirements on all manufacturers placing limits on pH, free fatty acid concentrations and globule size (both mean droplet size and the population of large fat globules larger than 5 micrometers). Recent animal data has shown pathophysiologic changes in vital organs for lipids that fall outside the USP-proposed globule size limits. From a clinical perspective, newer lipid injectable emulsions show great promise in certain patient settings, most notably in the intensive care unit in both adults and infants. The clinical use of alternative oils, such as medium-chain triglycerides, fish oil and olive oil show benefits over conventional soybean oil formulations. In adults, for example, the administration of omega-fatty acids via soybean oil-based lipids produces a heightened inflammatory response via production of 2-series prostaglandins, whereas substitution of a portion of the lipid with omega-3 fatty acids via fish oil can favorably dampen the inflammatory response. In infants, for example, substitution of soybean oil with fish oil has recently been shown to reverse parenteral nutrition-associated liver disease. These advances should lead to safer infusion therapy in patients receiving lipid injectable emulsions.

Animals↗
PubMed2005

Physical compatibility of neonatal total parenteral nutrient admixtures containing organic calcium and inorganic phosphate salts.

PURPOSE: The compatibility of calcium and phosphate salts in total parenteral nutrient (TPN) admixtures at the highest concentrations recommended for preterm and term infants was studied. METHODS: Particulate matter from eight different macronutrient combinations was measured and counted (range, 1.8-50 mum) by a laser-based, single-particle optical sensing technique. Measurements were performed at four intervals after compounding the formulations under aseptic conditions (within 1 hour of preparation and at 6, 24, and 30 hours) at 23-27 degrees C. The number of particles measuring >or=5, >or=10, and >or=25 microm per milliliter of TPN admixture was recorded. Detailed visual inspections were also performed at these intervals, and pH was measured at the beginning (time 0) and end of the study (30 hours). Precipitated material was characterized by polarized microscopy and infrared spectroscopy. RESULTS: The TPN admixture with the lowest concentration of amino acids (0.5%), as well as the highest pH, resulted in significant growth of particulate matter over time. At 30 hours, the particle growth was accompanied by visible evidence of precipitation, which was confirmed to be dibasic calcium phosphate. Neither significant particle growth nor precipitation was noted in the remaining seven formulations, which had amino acid concentrations of 1-4%. CONCLUSION: Commonly used organic calcium and inorganic phosphate salts in cysteine-added, lipid-free TPN formulations at the highest recommended amounts for neonates were compatible when the amino acid concentration was between 1% and 4% and the dextrose concentration was 5% or 10%. The salts remained compatible for up to 30 hours at a room temperature of up to 27 degrees C. Precipitation of dibasic calcium phosphate occurred with lower amino acid concentrations and higher pH values.

Amino Acids↗
PubMed2005

Pathological consequences from the infusion of unstable lipid emulsion admixtures in guinea pigs.

The pathophysiologic effects of infusing unstable lipid emulsions are unclear, but these were shown to cause reticuloendothelial system (RES) dysfunction in animals and humans. We investigated the effects of unstable lipid emulsions in RES organs defined by two levels of the percent fat >5 microm (percentage of fat, PFAT>5 microm) in a guinea pig model. Two identical injectable lipid emulsions with differing (stable versus unstable) PFAT >5 microm levels, were infused for over 24h into two groups of animals (n=5/group). The PFAT>5 microm concentration was measured before and at the end of the infusion to ascertain the dose range of enlarged fat globules in each group. Animals were euthanized and specimens from the upper, middle and lower lung, and a single liver sample were examined histologically and for micromolar concentrations of malondialdehyde (MDA) per gram (micromol(-1)g) of wet tissue. The PFAT>5 microm concentrations pre-infusion were 0.004+/-0.001 and 2.418+/-0.273 for the stable and unstable injectable lipid emulsions respectively. At 24 h, the PFAT>5 microm level increased in both the groups (stable: 0.161+/-0.008; unstable: 7.861+/-0.291). MDA concentrations were significantly higher in the lungs of animals receiving the unstable (47.2+/-26.2 micromol(-1)g) versus stable (32.4+/-11.2 micromol(-1)g) injectable lipid emulsions (P=0.033), but was not different for the liver specimens (stable: 16.9+/-7.6 micromol(-1)g versus unstable: 17.7+/-2.2 micromol(-1)g, P=0.944). These preliminary data suggest that infusion of unstable injectable lipid emulsions has pathological consequences showing greater evidence of oxidative stress in the lungs.

Animals↗
PubMed2005

Stability and compatibility assessment techniques for total parenteral nutrition admixtures: setting the bar according to pharmacopeial standards.

PURPOSE OF REVIEW: The stability and compatibility of total parenteral nutrition mixtures compounded for patients requiring nutritional support is paramount to their safety on intravenous infusion. The most significant pharmaceutical issues associated with mixing total parenteral nutrition formulations affecting their safety involve the stability of lipid-injectable emulsions and the compatibility of calcium and phosphate salts. Methods of analysis for stability and compatibility have varied, and the assessments have mostly been largely qualitative. RECENT FINDINGS: Although pharmacopeial standards have been primarily applicable to pharmaceutical manufacturers, recent efforts by the United States Pharmacopeia have been directed at standardizing pharmacy practices involved in the safe mixing of compounded sterile preparations. The adoption of chapter 797 entitled 'Pharmaceutical compounding - sterile preparations' on 1 January 2004 has had a dramatic impact on pharmacy practice in the United States. More recently, the United States Pharmacopeia has also proposed a new chapter 729 entitled 'Globule size distribution in lipid-injectable emulsions', setting specific limits on the sizes and concentrations of lipid droplets in the formulation, which may have implications for all-in-one mixtures. Finally, new efforts are under way to establish limits on the level of acceptable amounts of particulates intrinsically introduced by the manufacturer, and thus may have ramifications for particulates extrinsically introduced or initiated during compounding by the pharmacist. SUMMARY: With careful monitoring and the development of appropriate pharmacopeial-based specifications that limit the size and concentration of large-diameter fat globules and eliminate the possibility of dibasic calcium phosphate precipitates, improved patient outcomes may be achieved.

Drug Compounding↗
PubMed2004

Fat-globule size in a propofol emulsion containing sodium metabisulfite.

PURPOSE: The size distribution of fat globules from previously unopened, unexpired vials of Gensia Sicor's 1% propofol injectable lipid emulsion was studied. METHODS: Fat globules in 20-mL samples from 50- and 100-mL vials of Gensia Sicor's 1% propofol emulsion containing 0.025% sodium metabisulfite were measured and counted by a laser-based, single-particle optical sensing technique. Measurements were performed during May 2001, June 2002, and October 2002, corresponding, respectively, to 17-21, 5-9, and 1-5 months before the vials' expiration dates, depending on the lot. Between measurements, the vials were stored at 4-22 degrees C. It was assumed that the pH for all lots was 4.5-6.4. Two separate lots of the innovator propofol emulsion (AstraZeneca) containing EDTA and having a labeled pH of 7.0-8.5 were analyzed in October 2002 in a post hoc assessment as the vials neared their expiration date. RESULTS: In May 2001, the volume-weighted percentage of fat globules with a diameter of >5 microm (PFAT5) was <0.05% for all seven Gensia Sicor lots. In four of the lots, PFAT5 increased significantly between May 2001 and June 2002. In all seven lots, PFAT5 increased significantly between May 2001 and October 2002. The two lots of the AstraZeneca product, tested two or three months before expiration, had low PFAT5 values. CONCLUSION: In samples from unopened, unexpired, and properly stored vials of Gensia Sicor propofol formulated at pH 4.5-6.4, PFAT5 increased over 18 months and in most cases exceeded 0.05% by the end of the study.

Analysis of Variance↗
PubMed2002

The influence of medium-chain triglycerides on the stability of all-in-one formulations.

When mixed with parenteral nutrients as an all-in-one admixture, previous data have demonstrated that lipid emulsions composed of medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs) yield more stable formulations compared with those compounded with pure LCT lipid emulsions. We investigated the physical stability of various preparations of intravenous lipid emulsions as all-in-one admixtures. Each final lipid emulsion used to compound the all-in-one formulation was a 20% w/v mixture containing MCTs and LCTs as either a single emulsion containing both triglycerides, or an emulsion made extemporaneously from separate starting emulsions of pure MCT and LCT. The first emulsion was composed of a 50:50 (by weight) physical mixture of MCTs and LCTs, and consisted of 50% MCT:40% omega-6 LCT (soybean oil):10% omega-3 LCT (fish oil) that was available as a single 20% w/v lipid emulsion. The second and third emulsions were specially prepared from separate stock dispersions containing pure 20% w/v MCT and pure 20% w/v LCT (soybean oil) lipid emulsions, and were made in volume ratios of 75% MCT:25% omega-6 LCT and 50% MCT:50% omega-6 LCT, respectively. This was done in order to investigate whether the method of emulsion preparation and/or ratio of MCT to LCT influenced all-in-one admixture stability. Each all-in-one admixture was studied at four intervals over 30 h at room temperature conditions by light extinction (or obscuration) using a single-particle optical sensing (LE/SPOS) technique. The data, performed in duplicate at each interval, is expressed as the volume-weighted percent of fat (PFAT) globules >5 microm. The results confirm the stabilizing effects of MCTs when made as a physical oil mixture as a single lipid emulsion. However, stabilization is lost if the MCT and LCT emulsions are mixed from separate starting emulsions and then compounded as an all-in-one formulation. The extemporaneous mixing of commercial lipid emulsions is not recommended.

Drug Combinations↗
PubMedDate not supplied

Compounding TPN admixtures: then and now.

Compounding TPN admixtures has significantly developed since the first clinical reports by Dr. Dudrick and colleagues from the University of Pennsylvania approximately 35 years ago. Today, the responsibility for the compounding of sage parenteral nutrition admixtures for patients incapable of oral or enteral nutrition primarily rests with the pharmacy department. Although others may influence the desirable components to be contained therin, no one is more qualified to deal with the physicochemical issues and aseptic technique compounding requirements than a registered pharmacist. In fact, the United States Pharmacopeia (USP) , the official drug compendium in the US since 1906, has published Chapter 797 entitled "Pharmaceutical Compounding--Sterile Preparations", enforceable by the FDA, and makes clear the role of the pharmacist in the compounding of safe parenteral admixtures. Ultimately, after careful pharmaceutical review of the final formulation, the composition of the final admixture for infusion will be determined based on the ability to safely compound the prescribed additives in the desired quantities of a specified volume of sterile fluid. There will always be instances, where, for example the patient's needs cannot be safely met through the TPN admixture, primarily because of stability, compatibility and/or sterility issues. When this occurs, suitable alternative methods of delivering the additives in question must be sought so as not to compromise the safety issues of the final TPN infusion. Although there have been many advances in the development of nutritional additives, compounding devices, and containers, significant safety issues continue to arise necessitating further modification of paretneral nutrition protocols. ASPEN, through periodic reviews of tis published guidelines, such as the 1998 Safe Practices for Parenteral Nutrition Formulations, is in a key position to keep nutrition support clinicians abreast of the central issues affecting the safety of TPN therapy.(Journal of Parenteral and Enteral Nutrition

Drug Compounding↗
PubMedDate not supplied

At the bedside.

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Catholicism↗