Evaluation of official instrumental methods for the determination of particulate matter contamination in large volume parenteral solutions

The distribution pattern of particle contamination in nine different types of LV parenteral solutions and the possibility of correlating the counts made with two official instruments (Coulter Counter and HIAC) were studied. Two hundred containers of LV parenteral solutions (corresponding to 40 batches) produced in Italy, were sampled. Each bottle was submitted to HIAC and Coulter Counter countings, for particle sizes ranging between 2 and 25 micron. For about 50% of the products, the two straight lines that represent the distribution of particle contamination obtained with the two methods did not cross-over within the studied size range, the Coulter Counter counts always proving higher than the HIAC ones. In the other cases, the cross-over point of the two lines occurred at varying size levels. Statistical analysis of the results pointed to a relationship between the contamination values obtained with the two counting methods for sizes ranging between 2 and 5 micron, but there was no correlation for sizes equal to, or higher than, 10 micron. From the maximum contamination levels established by the BP and the FU IX for the HIAC method, the corresponding values were calculated for the Coulter Counter method. Similarly the values were calculated the HIAC method based on the maximum values set for the Coulter Counter.     

Osmolality of parenteral solutions.

Osmolality-concentration profiles for individual and mixed solute systems are presented. Linear relationships between osmolality and concentration held true in all systems examined at concentrations below 0.2 molal levels. At higher concentrations, linearity existed only in select systems. Deviations from linearity can be greater or less than extrapolated values. In view of the need to determine an osmolarity conversion factor for each parenteral formulation and the many errors possible in the use of these values, adoption of osmolality values for labeling parenteral products rather than osmolarity, as stipulated in USP XIX-NF XIV third supplement, strongly recommended.     

Stability of parenteral solutions of tobramycin sulfate.

The stability and physical compatibility of tobramycin sulfate in commonly used intravenous fluids were evaluated; in addition, pH values were obtained on 1 mg/ml tobramycin solutions, and microbiological potencies were obtained on 1 mg/ml and 0.2 mg/ml concentrations for 24- and 48-hour periods at 25 C. Most solutions were stable for 48 hours at room temperature. However, it is recommended that solutions of tobramycin sulfate be discarded after 24 hours to minimize the potential for inadvertent introduction of microorganisms during manipulations in the hospital environment.     

Myelin basic protein-mRNA used to monitor trimethyltin neurotoxicity in rats.

Trimethyltin (TMT) is an alkyltin that targets neurons of the limbic system. A gene probe (i.e., mRNA) for myelin basic protein (MBP), a major component of central nervous system myelin, was used to monitor this toxic neuropathy in Sprague-Dawley rats. Animals were administered a single intraperitoneal injection of TMT-hydroxide at a neuropathic (8.0 mg/kg/body wt) or nonneuropathic (0.8 mg/kg/body wt) dose and sampled at 1, 3, or 7 days postexposure to correlate the progression of hippocampal neuropathology with probe (i.e., MBP-mRNA) levels. Microscopic examination of the brain showed only moderate but progressive damage over the 7-day postexposure period in animals treated with the neuropathic dose. Neuronal loss was first observed in the dendate gyrus and CA4 at 1 day postexposure, and progressed to the CA3c sector at 3 and 7 days postexposure. Elsewhere in the brain, minimal involvement of the entorhinal cortex neurons occurred 3 days postexposure and intensified by 7 days. No histological damage was seen at the nonneuropathic (0.8 mg/kg) dose. For gene probe analysis, the brain was divided into anterior and posterior halves. In rats treated with the neuropathic dose of TMT, the anterior brain showed progressive depressions of MBP-mRNA levels over the 1-, 3-, and 7-day postexposure period that correlated with increasing hippocampal neuropathology. The posterior brain showed no significant changes in MBP-mRNA levels with respect to that of controls over the same time period. At the nonneuropathic dose (0.8 mg/kg) a significant depression of MBP-mRNA levels occurred in the anterior brain at 7 days postexposure in the absence of overt histological damage.     

Availability of insulin from parenteral nutrient solutions.

The effect of the following variables on insulin loss from total parenteral nutrient solutions was examined: (1) time of infusion sample; (2) insulin concentration; (3) amino acid or polypeptide source; (4) electrolytes and vitamins; (5) inline filters; (6) glass and polyvinyl chloride (PVC) infusion containers; and (7) human albumin. I125-tagged insulin was added to various parenteral nutrient solutions in liter containers. These solutions were prepared and drained to simulate actual clinical use. The drained solutions were collected and measured for radioactivity, and the percent of insulin remaining in the infusion container was calculated. Basic solutions of amino acids and protein hydrolysates in dextrose with 30 units of insulin failed to deliver approximately 44 to 47% of the added insulin. Varying the concentration of insulin had a small but statistically significant effect on the degree of insulin loss. The use of inline filters and PVC bags caused an even greater loss of insulin. The addition of albumin or electrolytes and vitamins decreased the insulin loss.     

Interactions of parenteral solutions with sulphur-treated glass bottles.

Concern about limited surface durability has been the main reasons for recommendations by advisory committees and government health authorities, not to reu-use sulphur-treated soda-lime glass (type II) bottles for intravenous solutions. In order to contribute specific data, the interactions of slightly acid and neutral parenteral solutions with ammonium sulphate-treated type II glass bottles have been investigated. It was established that the amounts of silica, sodium and calcium released into the solution are not greater than the potential background contamination from the raw materials. The number of particles in the solution was well below the limits set by the British Pharmacopoieia and not much higher than the lowest background count practically achievable. On an average, bottle surfaces released less material after the first time of use. Bottle-to-bottle variations revealed by scanning electron microscopy point at problems in achieving smooth, evenly surface-treated bottle surfaces during bottle manufacture.     

Stability of fluconazole and amino acids in parenteral nutrient solutions.

The stability of fluconazole and amino acids in parenteral nutrient (PN) solutions was studied. Amino acids at three concentrations (1.0%, 2.5%, and 5.0%) with 25% dextrose injection were combined with a high (1.75 mg/mL) or a low (0.5 mg/mL) concentration of fluconazole to form six combinations of PN solution and fluconazole. The solutions were visually inspected for precipitate, color change, or gas formation and tested for pH. By using high-performance liquid chromatography, the solutions were assayed for fluconazole concentration at zero, one, and two hours after preparation. The PN solution containing fluconazole 1.75 mg/mL and 5.0% amino acids was assayed for 14 amino acids at the same time points. There was no visual evidence of incompatibility in any of the fluconazole and PN solutions, and the pH of the solutions did not vary appreciably throughout the study period. The mean percentage of initial fluconazole concentration remaining at one and two hours was greater than 97% for all of the solutions studied. The mean percentage of initial amino acid concentration remaining at one and two hours was greater than 93% for each of the 14 amino acids assayed. When fluconazole 0.5 mg/mL or 1.75 mg/mL is mixed with PN solution containing 1.0%, 2.5%, or 5.0% amino acids and 25% dextrose injection, both fluconazole and amino acids are stable for up to two hours.     

Measured versus estimated aluminum content of parenteral nutrient solutions.

PURPOSE: A study was conducted to directly measure the aluminum concentration in a select number of parenteral nutrient (PN) solutions and to compare this value with the calculated dose using the concentrations reported by the manufacturer. METHODS: Fifty 2.5-mL samples were prepared for analysis and were obtained from PN solutions prepared for adult and pediatric/neonatal patients. Intravenous large-volume parenterals were used as controls. Samples were sent to two different reference laboratories. Batch 1 included 26 samples, 22 from PN solutions, 1 control, and 3 paired (duplicate) samples selected from the 22 PN bags. Because 8 of the samples were lost to analysis, a second batch of samples was included. Batch 2 consisted of 24 samples from 4 PN solutions and 2 controls. Batch 2 was composed of four aliquots from each solution that were divided equally and sent to the two laboratories. RESULTS: Twenty-three values were used in the statistical analysis. The results showed that only two of the adult PN solutions equaled or exceeded the threshold set by the Food and Drug Administration (FDA) for measured aluminum exposure. The measured concentration of aluminum for all six of the pediatric and neonatal solutions met or exceeded the FDA threshold; however, this value was much lower than what had been estimated using the labeled aluminum concentration at expiry. CONCLUSION: In PN solutions expected to have a moderately high concentration of aluminum, the measured amount of aluminum was far less than the amount that would be estimated by calculation using the labeled concentrations of aluminum in each of the ingredients.     

Pharmaceutical analysis and standardization of gimantan parenteral dosage form

The objective of this investigation was to develop methods for the pharmaceutical analysis of a parenteral dosage form of gimantan, a new anti-Parkinson’s drug. The physicochemical properties of gimantan solution for injection have been investigated. Methods for the determination of the impurity content and the quantitative drug assay were developed based on thin-layer chromatography (TLC) and gas chromatography (GC), respectively. The drug was identified using TLC and GC simultaneously with the purity evaluation and quantitative determination of gimantan. The stability during storage has been studied. The quality standards for gimantan parenteral dosage form have been developed.     

全胃肠外营养217例并发症分析

目的探讨全胃肠外营养（TPN）治疗的并发症发生的原因及防治方法。方法对我院1998年至2004年间217例TPN治疗的并发症分析。结果48例发生并发症，分别为导管并发症9例，感染并发症12例，代谢并发症8例，肝胆并发症18例，电解质紊乱8例，微量元素缺乏4例，部分患者同时出现两种以上并发症。结论严格的无菌操作、定期的临床监测、营养液配方的及时调整和良好的护理是防止并发症发生的关键。     

Stability of propofol with parenteral nutrient solutions during simulated Y-site injection.

The stability of propofol in three parenteral nutrient (PN) solutions was studied. Nine combinations of three PN solutions (with amino acid concentrations of 1.5, 2.5, and 5.0%) and three propofol concentrations (0.5, 2.0, and 3.0 mg/mL) were prepared in triplicate and stored at 22 degrees C under fluorescent light. Duplicate samples were visually inspected for color changes, precipitation, or gas formation, and the pH of the samples was determined. These samples were evaluated for propofol content by high-performance liquid chromatography at zero, one, three, and five hours. The stability of the vehicle for propofol injection (similar in composition to fat emulsion) was evaluated by visual inspection, pH determination, and particle-size measurements at zero, one, three, and five hours. The concentration of propofol in all of the propofol-PN combinations remained greater than 90% of the initial concentration except for the combination of propofol 0.5 mg/mL and the 1.5% amino acid PN solution, which contained only 72% of the initial propofol concentration five hours after the start of the study. Visual examination revealed no evidence of color change, precipitation, gas formation, creaming, or streaking in any of the propofol-PN solution combinations. No substantial changes in pH occurred. The particle size of the vehicle for propofol remained relatively constant throughout the study period. Propofol 2 and 3 mg/mL was stable for five hours during simulated Y-site injection with PN solutions containing 1.5, 2.5, and 5% amino acids. Propofol 0.5 mg/mL was stable during simulated Y-site injection with the same PN nutrition solutions for five hours, except for the solution containing 1.5% amino acid.     

Effect of computer software on time required to prepare parenteral nutrient solutions

Pharmacist and technician times required for the preparation of parenteral nutrient (PN) solutions were studied before and after the introduction of a software package that is used with an automated compounder. At a 580-bed teaching hospital, work sampling was used to collect data on how time was spent by personnel in the i.v. admixture pharmacy during six-week periods before and after the introduction of software that calculates the quantities of PN solution ingredients on a computer-generated work sheet and prints labels. The second data-collection period began when the software had been in use for four months. In the second study period, there was a significant decrease (28%) in total pharmacist time spent per PN solution; the mean +/- S.D. pharmacist times per PN solution per day for the two study periods were 14.03 +/- 3.24 minutes and 10.12 +/- 1.61 minutes, respectively. There were also significant decreases in pharmacist time spent performing calculations, checking calculations, and typing labels. After introduction of the software, technicians spent significantly less time typing labels and pumping base solutions. Overall, technicians spent significantly less time per PN solution in the second study period (20.15 +/- 3.50 versus 17.82 +/- 1.94 minutes). Use of the software allowed pharmacist staffing in the i.v. admixture pharmacy to be reduced, and the pharmacy resources were reallocated toward the provision of clinical services. The generation of PN labels and calculation worksheets by computer software reduced pharmacist and technician time requirements for PN solution preparation.     

消毒剂应用过程被污染的监测与分析

目的了解消毒剂使用中的污染状况。方法将我院临床使用中的消毒剂60份（复方新洁灵,75%乙醇、安尔碘3种）随机分为观察组与对照组各30份。观察组开原装瓶注明启用日期,使用期限7d;对照组开原装瓶注明启用日期,使用期限14d,进行采样检测。比较2组细菌污染程度。结果使用中消毒剂的细菌污染例数随时间的延长而增加,观察组污染率为10%低于对照组的73.3%,差异有统计学意义（P〈0.01）。结论开启原装瓶消毒剂使用期限为7d,以保证消毒剂无细菌污染,有效控制医源性交叉感染的发生。