Parenteral Products Research Articles

Mechanism of 2-hydropropyl-beta-cyclodextrin in the stabilization of frozen formulations

Freezing of commonly used parenteral products to increase pharmaceutical stability for cost-saving purposes is a common practice in patient care. However, frozen meropenem, a model drug, in saline has a shelf life of less than a month due to the low glass transition temperature (Tg′): below −40°C. When meropenem is formulated with the 2-hydroxypropyl-β-cyclodextrin (HPBC) the shelf life (⩾90% potency) is extrapolated to be greater than one year at −25°C based on data for storage at 6months. The mechanisms that may explain meropenem–HPBC formulation frozen stability include vitrification and/or formation of an inclusion complex. Although NMR data indicated complexation of meropenem by HPBC in a ratio of 0.6:1, inclusion was unlikely to be the mechanism as stability was not extended to the thawed solutions. Therefore, vitrification is concluded to be the stabilization mechanism. The Tg′ for meropenem–HPBC (13.3%) formulation at pH 7.9 was −17.75°C which was similar to that of a meropenem solution formulated with a known vitrifying agent, Dextran 40. This higher Tg′ for HPBC was unexpected based on trends predicted by the Fox-Flory equation. Trial formulations containing either Dextran 1, Dextran 40, hydroxyethyl starch, or sulfobutyl-beta-cyclodextrin heptasodium (Captisol®) were also unable to stabilize meropenem as the Tg′ values were below the frozen storage temperature. Upon 6-month storage, potency losses were −3.0% and −7.7% for meropenem frozen premix formulated in 13.3% HPBC (pH 7.9) at −25 and −20°C storage, respectively; versus −31.2% and −60.8% for controls. Frozen premixes with high ionic strength (containing NaCl or Captisol®) and/or at pH 7.3 were also found to be unstable.

Incidence of Nonconfounded Post–Computed Tomography Acute Kidney Injury in Hospitalized Patients with Stable Renal Function Receiving Intravenous Iodinated Contrast Material

The purpose of our investigation was to determine the frequency of proximate acute and chronic confounding risk factors for acute kidney injury (AKI) in a cohort of adult hospitalized patients with stable renal function who developed AKI following an intravenous (IV) contrast-enhanced computed tomography (CT) examination. Institutional review board approval was obtained for this retrospective, Health Insurance Portability and Accountability Act-compliant investigation. Overall, 100 adult inpatients (50 males [mean age = 61 years, range: 24-94 years] and 50 females [mean age = 60 years, range: 20-95 years]) with stable pre-CT renal function who developed post-CT AKI using the Acute Kidney Injury Network (AKIN) laboratory criteria following an IV contrast-enhanced CT examination comprised the study population. Electronic International Classification of Disease-9 analysis followed by a comprehensive manual electronic medical record review was systematically performed by 5 radiologists to identify known acute (n = 24, within 5 days before or 3 days after CT) and chronic (n = 21) risk factors for AKI other than contrast material administration that might confound a diagnosis of contrast-induced nephrotoxicity. Descriptive statistics were performed. Of 100 inpatients with post-CT AKI, 99 (99%) had 1 or more acute risk factor(s) for AKI other than contrast material administration (median = 3 risk factors, range: 0-8) and 86 (86%) had one or more chronic risk factor(s) for AKI (median = 2 risk factors, range: 0-7). The median number of risk factors (acute or chronic) per patient was 5 (range: 1-13). Only 1 inpatient (1%) developed post-CT AKI without a confounding acute risk factor (estimated glomerular filtration rate = 62-71 mL/min/1.73 m(2), 4 chronic risk factors, and CT 7 days after pancreaticoduodenectomy). The most common acute risk factors were nephrotoxic medications (83%) and parenteral blood product administration (30%). The most common chronic risk factors were hypertension (59%) and chronic kidney disease (56%). Nonconfounded post-CT AKI is rare in hospitalized adults with stable renal function who have been exposed to IV low- or iso-osmolality iodinated contrast material.

Measurement of subvisible particulates in lyophilised Erwinia chrysanthemi L-asparaginase and relationship with clinical experience.

In order to generate further characterisation data for the lyophilised product Erwinia chrysanthemi l-asparaginase, reconstituted drug product (DP; marketed as Erwinase or Erwinaze) was analysed for subvisible (2–10 μm) particulate content using both the light obscuration (LO) method and the newer flow-imaging microscopy (FIM) technique. No correlation of subvisible particulate counts exists between FIM and LO nor do the counts correlate with activity at both release and on stability. The subvisible particulate content of lyophilised Erwinia l-asparaginase appears to be consistent and stable over time and in line with other parenteral biopharmaceutical products. The majority (ca. 75%) of subvisible particulates in l-asparaginase DP were at the low end of the measurement range by FIM (2–4 μm). In this size range, FIM was unable to definitively classify the particulates as either protein or non-protein. More sensitive measurement techniques would be needed to classify the particulates in lyophilised l-asparaginase into type (protein and non-protein), so the LO technique has been chosen for on-going DP analyses. E. chrysanthemi l-asparaginase has a lower rate of hypersensitivity compared with native Escherichia coli preparations, but a subset of patients develop hypersensitivity to the Erwinia enzyme. A DP lot that had subvisible particulate counts on the upper end of the measurement range by both LO and FIM had the same incidence of allergic hypersensitivity in clinical experience as lots at all levels of observed subvisible particulate content, suggesting that the presence of l-asparaginase subvisible particulates is not important with respect to allergic response.

Investigation for the Effects of Omega Fatty Acid and Glutamine-L-Alanine on Morbidity and Mortality in the Critically ILL Patients after Major Abdominal Surgery

Background & Objectives: This study investigated the effects for the addition of omega 3 fatty acids and glutamine-L-alanine to the standard enteral and/or parenteral nutrition regimen on infection and mortality in the critically ill patients after major abdominal surgery. Methods: This is a prospective, randomized, single center study. A total of 43 patients (age range: 18-85 years), who were in the critical care unit after major abdominal surgery, were included. Patients were divided into two groups according to simple randomized selection [Control group, n=20; Study Group, n=23 (omega3 fatty acids and glutamine-L-alanine)] and were monitored for 21 days. Patients were examined for the assessment of APACHE II Score and existence of ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) requiring mechanical ventilation. In addition to standard enteral or parenteral nutrition, patients in the study group were given parenteral pharmaconutrition products for 10 days postoperatively. Groups were compared for the duration of mechanical ventilation, duration of stay in the intensive care unit and hospitalization, and mortality. Laboratory parameters including CRP, TNF, IL6, IL8, nitrogen balance, albumin, and total lymphocyte count were recorded. Results:Although the mean APACHE score was higher in study group in which patients received omega-3 fatty acids and glutamine-L-alanine support, the clinical infection rate seemed to decrease insignificantly. Conclusions: A clinically decreased rate of infection was observed in patients with a high APACHE II score, or who received omega-3 fatty acids, glutamine-L-alanine, are required to be administered more selectively and in larger patient groups in different doses and in combination protocols in accordance with the current pharmaconutritional support and in different timing combinations, including preoperative period

Tu1132 High Incidence of Selenium Deficiency in Children With Gastrointestinal or Neurological Dysfunction Treated With Parenteral Nutrition and/or Enteral Medical Nutritional Products

Tu1132 High Incidence of Selenium Deficiency in Children With Gastrointestinal or Neurological Dysfunction Treated With Parenteral Nutrition and/or Enteral Medical Nutritional Products

Colistin and Polymyxin B: Peas in a Pod, or Chalk and Cheese?

Colistin and polymyxin B have indistinguishable microbiological activity in vitro, but they differ in the form administered parenterally to patients. Polymyxin B is administered directly as the active antibiotic, whereas colistin is administered as the inactive prodrug, colistin methanesulfonate (CMS). CMS must be converted to colistin in vivo, but this occurs slowly and incompletely. Here we summarize the key differences between parenteral CMS/colistin and polymyxin B, and highlight the clinical implications. We put forth the view that overall polymyxin B has superior clinical pharmacological properties compared with CMS/colistin. We propose that in countries such as the United States where parenteral products of both colistin and polymyxin B are available, prospective studies should be conducted to formally examine their relative efficacy and safety in various types of infections and patients. In the meantime, where clinicians have access to both polymyxins, they should carefully consider the relative merits of each in a given circumstance.

Zinc Deficiency in a Parenteral Nutrition–Dependent Patient During a Parenteral Trace Element Product Shortage

Parenteral nutrition product shortages are common and place vulnerable patients at risk for nutrient deficiencies. This case report describes a parenteral nutrition-dependent patient who was found to have zinc deficiency during a parenteral nutrition product shortage. The management of the patient's zinc deficiency is described.

Parenteral nutrition product recalled following potential contamination

Parenteral nutrition product recalled following potential contamination

Parenteral nutrition product recall

Parenteral nutrition product recall

High-Voltage Leak Detection of a Parenteral Proteinaceous Solution Product Packaged in Form-Fill-Seal Plastic Laminate Bags. Part 1. Method Development and Validation

In Part 1 of this three-part research series, a leak test performed using high-voltage leak detection (HVLD) technology, also referred to as an electrical conductivity and capacitance leak test, was developed and validated for container-closure integrity verification of a small-volume laminate plastic bag containing an aqueous solution for injection. The sterile parenteral product is the rapid-acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®, by Novo Nordisk A/S, Bagsværd, Denmark). The aseptically filled and sealed package is designed to preserve product sterility through expiry. Method development and validation work incorporated positive control packages with a single hole laser-drilled through the laminate film of each bag. A unique HVLD method characterized by specific high-voltage and potentiometer set points was established for testing bags positioned in each of three possible orientations as they are conveyed through the instrument's test zone in each of two possible directions-resulting in a total of six different test method options. Validation study results successfully demonstrated the ability of all six methods to accurately and reliably detect those packages with laser-drilled holes from 2.5-11.2 μm in nominal diameter. Part 2 of this series will further explore HVLD test results as a function of package seal and product storage variables. The final Part 3 will report the impact of HVLD exposure on product physico-chemical stability. In this Part 1 of a three-part research series, a leak test method based on electrical conductivity and capacitance, called high voltage leak detection (HVLD), was used to find leaks in small plastic bags filled with an insulin pharmaceutical solution for human injection by Novo Nordisk A/S (Bagsværd, Denmark). To perform the test, the package is electrically grounded while being conveyed past an electrode linked to a high-voltage, low-amperage transformer. The instrument measures the current that passes from the transformer to the electrode, through the packaged product and along the package walls, to the ground. Plastic packages without defect are relatively nonconductive and yield a low voltage reading; a leaking package with electrically conductive solution located in or near the leak triggers a spike in voltage reading. Test methods were optimized and validated, enabling the detection of leaking packages with holes as small as 2.5 μm in diameter. Part 2 of this series will further explore HVLD test results as a function of package seal and product storage variables. The final Part 3 will report the impact of HVLD exposure on product stability.

High-Voltage Leak Detection of a Parenteral Proteinaceous Solution Product Packaged in Form-Fill-Seal Plastic Laminate Bags. Part 2. Method Performance as a Function of Heat Seal Defects, Product-Package Refrigeration, and Package Plastic Laminate Lot

Part 1 of this three-part research series detailed the development and validation of a high-voltage leak detection test (HVLD, also known as an electrical conductivity and capacitance test) for verifying the container-closure integrity of a small-volume laminate plastic bag containing an aqueous solution formulation of the rapid-acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®) by Novo Nordisk A/S, Bagsværd, Denmark. Leak detection capability was verified using positive controls each with a single laser-drilled hole in the bag film face. In this Part 2, HVLD leak detection capability was further explored in four separate studies. Study 1 investigated the ability of HVLD to detect weaknesses and/or gaps in the bag heat seal. Study 2 checked the HVLD detection of bag holes in packages stored 4 days at ambient conditions followed by 17 days at refrigeration. Study 3 examined HVLD test results for packages tested when cold. Study 4 compared HVLD test results as a function of bag plastic film lots. The final Part 3 of this series will report the impact of HVLD exposure on product visual appearance and chemical stability. In Part 1 of this three-part series, a leak test method based on electrical conductivity and capacitance, also called high-voltage leak detection (HVLD), was used to find leaks in small plastic bags filled with a solution for injection of the rapid-acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®) by Novo Nordisk A/S, Bagsværd, Denmark. In this Part 2, HVLD leak detection capability was further explored in four separate studies. Study 1 investigated the ability of HVLD to detect bag heat seal leaks. Study 2 checked HVLD's ability to detect bag holes after a total of 21 days at ambient plus refrigerated temperatures. Study 3 looked to see if HVLD results changed for packages tested when still cold. Study 4 compared HVLD results for multiple bag plastic film lots. The final Part 3 of this series will report any evidence of drug component degradation caused by HVLD exposure.

High-Voltage Leak Detection of a Parenteral Proteinaceous Solution Product Packaged in Form-Fill-Seal Plastic Laminate Bags. Part 3. Chemical Stability and Visual Appearance of a Protein-Based Aqueous Solution for Injection as a Function of HVLD Exposure

This Part 3 of this three-part research series reports the impact of high-voltage leak detection (HVLD) exposure on the physico-chemical stability of the packaged product. The product, intended for human administration by injection, is an aqueous solution formulation of the rapid acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®) by Novo Nordisk A/S, Bagsværd, Denmark. The package is a small-volume form-fill-seal plastic laminate bag. Product-packages exposed to HVLD were compared to unexposed product after storage for 9 months at recommended storage conditions of 5 ± 3 °C. No differences in active ingredient or degradation products assays were noted. No changes in any other stability indicating parameter results were observed. This report concludes this three-part series. Part 1 documented HVLD method development and validation work. Part 2 explored the impact of various package material, package temperature, and package storage conditions on HVLD test results. Detection of leaks in the bag seal area was investigated. In conclusion, HVLD is reported to be a validatable leak test method suitable for rapid, nondestructive container-closure integrity evaluation of the subject product-package. In Part 1 of this three-part series, a leak test method based on electrical conductivity and capacitance, also called high-voltage leak detection (HVLD), was proven to find hole leaks in small plastic bags filled with a solution of insulin aspart intended for human injection (NovoRapid®/NovoLog® by Novo Nordisk A/S, Bagsværd, Denmark). In Part 2, the ability of the HVLD method to find other types of package leaks was tested, and the impact of package material and product storage temperature on HVLD results was explored. This final Part 3 checked how well the packaged protein drug solution maintained its potency after HVLD exposure over 9 months of storage under long-term stability conditions. Results showed that HVLD caused no harm to the product.

Contenants et contaminants en nutrition parentérale : l’aluminium, un revenant ?

Aluminium is a well-known potentially hazardous contaminant in parenteral preparation for dialysis or drug delivery. The main objective of the study is to assess aluminium exposure from chronic parenteral nutrition supply. The specific objectives of the study were (i) to assess aluminium concentration in parenteral nutrition compounds (n=26) and in hospital-made parenteral nutrition mixture (n=56), (ii) to compare aluminium concentration in nutrition products to the maximum allowable concentration (i.e. 25μg/L), and finally (iii) to compare the daily rate infused per kilogram of weight to the limit value recommended by American Society of Parenteral and Enteral Nutrition (i.e. 2μg.kg−1 per day). Aluminium content, assessed by atomic absorption spectrophotometry, was determined in parenteral nutrition compounds and in hospital-made parenteral nutrition admixtures to clinically stable patients undergoing total or partial parenteral nutrition. Aluminium concentration in fourteen parenteral nutrition compounds and all parenteral nutrition admixtures excessed 25μg/L. Furthermore, two thirds of patients were exposed to a rate of aluminium significantly upper than that recommended by the American Society of Parenteral and Enteral Nutrition (i.e. 2μg.kg-1 per day). This study shows that parenteral nutrition compounds and parenteral nutrition admixtures were overloaded in aluminium. A monograph specifying acceptable aluminium content of parenteral nutrition products seems necessary for further redaction of European pharmaceutical norm or guidance.

Recent Advances in Lipid-Based Formulation Technology

Lipid-based formulations encompass a wide variety of delivery modes and technologies, ranging from immediate release to sustained release formulations, from liquids to semi-solids, from crystalline suspensions to lipid solutions, from systems containing small-molecule active pharmaceutical ingredients (APIs) to those containing more complex peptide-based molecules, and finally from those intended for oral administrations through to topicals and parenterals. The flexibility of lipid formulation technologies provides the potential to modify pharmaceutical properties such as stability and ease of manufacture, and pharmacokinetic properties such as enhanced absorption and bioavailability, sustained exposure and targeted delivery. With the exception of liposomal technologies (that represent a class of delivery system in their own right and have not been considered here), much of the interest in lipid-based formulations has focused on their use to enhance the oral bioavailability of poorly water-soluble drugs. Drugs with low water solubility continue to present a formidable challenge to effective drug development (1) and commonly show poor, variable, and fooddependent absorption and bioavailability after oral administration. Whilst great strides have been made in lead optimization strategies to design-out the physicochemical properties that lead to low water solubility, in many cases, structural changes that increase solubility also result in unacceptable reductions in potency. Indeed, the majority of reports describing changes in the patterns of physicochemical properties for new drug discovery candidates suggest that trends towards low water solubility are increasing rather than decreasing (2,3). Formulation strategies that facilitate the ‘rescue’ of compounds with intrinsically low water solubility, and that provide for robust and reproducible exposure after oral administration, therefore remain an important weapon in the drug development armory. Several strategies that enable effective delivery of poorly water-soluble compounds are apparent (1) and, in general, may be stratified as technologies that modify solute–solute interactions in the solid state, that enhance solute–solvent interactions in solution, that promote dissolution via changes in surface area, or combinations of the three approaches. Formulation technologies to enhance solubility and dissolution rate include salt formulation,modification of crystal form (amorphous, cocrystals, polymorphs), particle size reduction/nanomilling, alteration of solution/solubilisation conditions (cosolvents, surfactants, cyclodextrins etc.), and approaches such as solid dispersions and lipidbased formulations that may, in practice, achieve a number of these goals. For example, many solid dispersion and lipid-based formulations contain drug in a non-crystalline (amorphous/molecularly dispersed) form, circumventing the challenge to solubility provided by the crystal lattice, and also provide for ongoing solubilisation or stabilization of supersaturation via the inclusion of surfactants, lipids and/or polymers. The current theme issue focuses on the potential utility of lipid-based formulations as a means of enhancing the oral bioavailability of poorly water-soluble drugs. In addition, several manuscripts provide insight into the broader application of lipid-based drug delivery technologies, for example, to facilitate parenteral or site-specific delivery of lipophilic compounds. This is not to suggest any inherent superiority of lipid-based formulation technologies over others, and the appropriate choice of an enabling technology is clearly drug specific. However, for poorly water-soluble lipophilic drugs, lipid-based formulations provide a tried and tested delivery solution to overcome poor and variable oral bioavailability and are increasingly being utilized as a vehicle to achieve modulated or targeted delivery. Nonetheless, whilst lipid-based formulations have been used to good effect in a range of oral and parenteral drug products (4), several challenges to their broader utility remain. These C. J. H. Porter (*) :H. D. Williams :N. L. Trevaskis Drug Delivery Disposition and Dynamics Monash Institute of Pharmaceutical Sciences Monash University (Parkville campus) Melbourne, Victoria, Australia e-mail: chris.porter@monash.edu

The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP)

The Product Quality Research Institute (PQRI) is a non-profit consortium of organizations working together to generate and share timely, relevant, and impactful information that advances drug product quality and development. The collaborative activities of PQRI participants have, in the case of orally inhaled and nasal drug products (OINDPs), resulted in comprehensive and widely-accepted recommendations for leachables assessments to help ensure patient safety with respect to this class of packaged drug products. These recommendations, which include scientifically justified safety thresholds for leachables, represent a significant milestone towards establishing standardized approaches for safety qualification of leachables in OINDP. To build on the success of the OINDP effort, PQRI's Parenteral and Ophthalmic Drug Products (PODP) Leachables and Extractables Working Group was formed to extrapolate the OINDP threshold concepts and best practice recommendations to other dosage forms with high concern for interaction with packaging/delivery systems. This article considers the general aspects of leachables and their safety assessment, introduces the PODP Work Plan and initial study Protocol, discusses the laboratory studies being conducted by the PODP Chemistry Team, outlines the strategy being developed by the PODP Toxicology Team for the safety qualification of PODP leachables, and considers the issues associated with application of the safety thresholds, particularly with respect to large-volume parenterals. Lastly, the unique leachables issues associated with biologics are described. The Product Quality Research Institute (PQRI) is a non-profit consortium involving industry organizations, academia, and regulatory agencies that together provide recommendations in support of regulatory guidance to advance drug product quality. The collaborative activities of the PQRI Orally Inhaled and Nasal Drug Products Leachables and Extractables Working Group resulted in a systematic and science-based approach to identify and qualify leachables, including the concept of safety thresholds. Concepts from this widely accepted approach, formally publicized in 2006, are being extrapolated to parenteral and ophthalmic drug products. This article provides an overview of extractables and leachables in drug products and biologics and discusses the PQRI Work Plan and Protocols developed by the PQRI Parenteral and Ophthalmic Drug Products Leachables and Extractables Working Group.

Perspectives on the PQRI Extractables and Leachables "Safety Thresholds and Best Practices" Recommendations for Inhalation Drug Products

In 2006, the Product Quality Research Institute's (PQRI) Leachables and Extractables Working Group released a comprehensive and detailed recommendation document related to leachables and extractables for inhalation drug products. The document includes best pharmaceutical development practice recommendations regarding container closure/delivery system component composition and selection, controlled extraction studies, drug product leachables studies, and routine extractables testing for component release. Also included in the document are two safety-based thresholds for leachables in inhalation drug products, the qualification threshold (QT) and the safety concern threshold (SCT), the first such safety-based thresholds for leachables in any drug product type. A process was described for converting the SCT into an analytically useful threshold for leachables/extractables characterization, the analytical evaluation threshold (AET), with consideration of individual drug product dosing parameters and container closure system component characteristics. This commentary presents the history and evolution of this recommendation document starting from the propellant changeover (chlorofluorocarbons to hydrofluorocarbons) in metered dose inhaler drug products, which helped prompt interest in inhalation drug product leachables, through the work process of the PQRI group. The overall positive acceptance of the PQRI recommendations is discussed, along with a brief summary of regulatory initiatives influenced by the recommendations. Also presented and discussed are certain key issues and questions that have arisen since the recommendation document was released. The extension and application of best practice recommendations to other high risk drug product types (e.g., large and small volume parenterals, ophthalmics), led by the PQRI Parenteral and Ophthalmic Drug Product Working Group, is introduced and considered. The recommendation document released by the Product Quality Research Institute's (PQRI) Leachables and Extractables Working Group in 2006 includes the first safety-based thresholds for leachables in any drug product type, along with comprehensive best practice recommendations for inhalation drug product pharmaceutical development related to extractables and leachables. The best practice recommendations encompass a number of important functional areas, including container closure/delivery system component composition and selection, controlled extraction studies, drug product leachables studies, and routine extractables testing for component release. This commentary presents the history and evolution of this recommendation document starting from the propellant changeover (chlorofluorocarbons to hydrofluorocarbons) in metered dose inhaler drug products, which helped prompt interest in inhalation drug product leachables, through the work process of the PQRI group. The overall positive acceptance of the PQRI recommendations is discussed, along with a brief summary of regulatory initiatives influenced by the recommendations. Also presented and discussed are certain key issues and questions that have arisen since the recommendation document was released. The extension and application of best practice recommendations to other drug product types (e.g., large- and small-volume parenterals, ophthalmics), led by the PQRI Parenteral and Ophthalmic Drug Product Working Group, is introduced and considered.

Extractables Characterization for Five Materials of Construction Representative of Packaging Systems Used for Parenteral and Ophthalmic Drug Products

Polymeric and elastomeric materials are commonly encountered in medical devices and packaging systems used to manufacture, store, deliver, and/or administer drug products. Characterizing extractables from such materials is a necessary step in establishing their suitability for use in these applications. In this study, five individual materials representative of polymers and elastomers commonly used in packaging systems and devices were extracted under conditions and with solvents that are relevant to parenteral and ophthalmic drug products (PODPs). Extraction methods included elevated temperature sealed vessel extraction, sonication, refluxing, and Soxhlet extraction. Extraction solvents included a low-pH (pH = 2.5) salt mixture, a high-pH (pH = 9.5) phosphate buffer, a 1/1 isopropanol/water mixture, isopropanol, and hexane. The resulting extracts were chemically characterized via spectroscopic and chromatographic means to establish the metal/trace element and organic extractables profiles. Additionally, the test articles themselves were tested for volatile organic substances. The results of this testing established the extractables profiles of the test articles, which are reported herein. Trends in the extractables, and their estimated concentrations, as a function of the extraction and testing methodologies are considered in the context of the use of the test article in medical applications and with respect to establishing best demonstrated practices for extractables profiling of materials used in PODP-related packaging systems and devices. Plastic and rubber materials are commonly encountered in medical devices and packaging/delivery systems for drug products. Characterizing the extractables from these materials is an important part of determining that they are suitable for use. In this study, five materials representative of plastics and rubbers used in packaging and medical devices were extracted by several means, and the extracts were analytically characterized to establish each material's profile of extracted organic compounds and trace element/metals. This information was utilized to make generalizations about the appropriateness of the test methods and the appropriate use of the test materials.

Parenteral Nutrition Amino Acids Product Shortage Considerations

Nutrition in Clinical PracticeVolume 28, Issue 4 p. 524-527 Product Shortage Consideration Parenteral Nutrition Amino Acids Product Shortage Considerations First published: 05 August 2013 https://doi.org/10.1177/0884533613498215Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume28, Issue4Gastrointestinal Disorders / Enteral NutritionAugust 2013Pages 524-527 RelatedInformation

Parenteral Nutrition Intravenous Fat Emulsions Product Shortage Considerations

Parenteral Nutrition Intravenous Fat Emulsions Product Shortage Considerations

Microscopy in Glass Corrosion Analysis of Parenteral Products

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.