United States Pharmacopeial Convention Research Articles

Database of Food Fraud Records: Summary of Data from 1980 to 2022

Food fraud prevention and detection remains a challenging problem, despite recent developments in regulatory and auditing requirements. In 2012, the United States Pharmacopeial Convention created a database of food ingredient fraud. The objective of this research was to report on updates made to the database structure and to provide an updated analysis of food fraud records. The restructured database was relational and included four tables: ingredients, adulterants, adulteration records, and references. Four adulteration record types were created to capture the variety of information that can be found in public food fraud reports. Information was searched and extracted from the peer-reviewed scientific literature, media publications, regulatory reports, judicial records, trade association reports, and other public sources covering 1980-present. Over an almost seven-year data entry period, a total of 15,575 records were entered, sourced primarily from the peer-reviewed literature and media reports. The percentage of records that included at least one potentially hazardous adulterant ranged from 34% to 60%, depending on the record type. The ingredients with the highest number of incident and inference records included fluid cow’s milk, extra virgin olive oil, honey, beef, and chili powder. The ingredient groups with the highest number of incident and inference records included Dairy Ingredients, Seafood Products, Meat and Poultry Products, Herbs, Spices, and Seasonings, Milk and Cream, and Alcoholic Beverages. This database was created to serve as a standardized source of information about publicly documented occurrences of food fraud and other information relevant to fraud risk to support food fraud vulnerability assessments, mitigation plans, and food safety plans. These data support the contention that food fraud presents a public health risk that should continue to be addressed by food safety systems worldwide.

A U.S. Pharmacopeia (USP) overview of Pan American botanicals used in dietary supplements and herbal medicines.

The United States Pharmacopeial Convention (USP) is a nonprofit, scientific, standard-setting organization, and world leader in establishing quality, purity, and testing standards for medicines, foods, and dietary supplements. USP quality standards are used in more than 140 countries and are legally recognized by more than 40 countries. Currently, there is renewed interest in herbal medicines globally, and health policies are being implemented worldwide for the use of complementary and traditional medicine. In response, USP has developed a robust body of monographs that can be used to guide industry and regulators in ensuring the quality and safety of botanical ingredients used in dietary supplements and herbal medicines. Throughout the Pan American regions, there is a strong tradition of using botanicals as herbal medicines and, as in other regions, a growing desire for botanical dietary supplements. This underscores the need for public quality standards to ensure quality, reduce the flow of substandard and adulterated products, and ensure public health and safety. In April 2022, USP launched the Pan America Botanical Dietary Supplements and Herbal Medicines Expert Panel, with experts representing 12 different countries. The Expert Panel's work focuses on developing quality control standards for the most important botanical ingredients used in the respective countries, ingredients that are also of global importance. This article provides an overview of the state of botanical dietary supplements and herbal medicines in different Pan American regions with a focus on the regulatory status of herbal products, the development of national quality and research initiatives, and policies related to agriculture conservation and sustainability, among other topics.

Development and Validation of a Method for the Analysis of Zinc Oxide in Cosmetic Matrices by Flame Atomic Absorption Spectroscopy

A fast and simple method for the extraction and Flame Atomic Absorption Spectroscopy (FAAS) quantification of ZnO in different cosmetic matrices, including lipsticks, water-in-oil foundations, and oil-in-water creams, was developed and validated, according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the United States Pharmacopeial Convention guidelines. The sample preparation consisted of an ultrasound-assisted ethanolic extraction of ZnO followed by digestion with 1 M nitric acid (HNO3). Samples were analyzed by Flame Atomic Absorption Spectroscopy (FAAS). Specificity, linearity, the limit of detection (LOD), the limit of quantification (LOQ), sensitivity, precision, and accuracy parameters were studied. The robustness of the method was evaluated with a five-variable Youden–Steiner model. The method was specific for ZnO, and the extraction procedure did not affect the stability of the signal compared to the background. The method was linear in the range 0.2–1.0 mg/L with LOD/LOQ values equal to 0.0156 (mg·L−1)/0.0473 (mg·L−1), 0.0098 (mg·L−1)/0.0297 (mg·L−1), 0.0113 (mg·L−1)/0.0341 (mg·L−1), and 0.0131 (mg·L−1)/0.0397 (mg·L−1), respectively, for raw material, lipstick, liquid foundation, and emulsion matrices. Regarding precision, the %RSD values were below 3.0% for repeatability and intermediate precision. Global reproducibility RSD was below 8.0% for all matrices. The percentage of recovery was not statistically different from 100% in all cases. The final concentration was found to be a critical variable for all matrices except for the raw material. The variables associated with the extraction step (ethanol volume, bath temperature, and extraction time) were critical in the extraction of liquid foundations and cream emulsions. The method reduces the number and concentration of mineral acids spent on the digestion of ZnO, and its application is extendable to raw materials. This development is an adequate tool for routine analysis and cosmetic quality control of chemically different products that contain ZnO as ultraviolet radiation (UV) filter, to guarantee regulatory compliance and ensure the safety and efficacy of products delivered to consumers.

Prioritizing Staff Safety

Most of us have been on airplane flights, so the following scene should be familiar: right before the plane takes off, the well-trained flight crew reviews the safety aspects of the aircraft with all passengers on board, including verbal instructions and a visual demonstration of how to “put your oxygen mask on first before helping others.” As you reflect on the directive to “put your oxygen mask on first,” you realize its importance—if you are incapacitated because of a lack of oxygen, you cannot help or save anyone else who may be in trouble. That statement speaks to the spirit of this special focus issue dedicated to staff safety. As perioperative nurses, how can we safely care for our patients, especially when they are most vulnerable, if we do not have a safe environment in which to take care of ourselves while delivering nursing care? We must not hesitate to “put our oxygen mask on first” so that we can provide exceptional safe surgical patient care. I am very excited, honored, and humbled to be the guest editor of this special focus issue on staff safety. During my nursing career, I have come to realize that as nurses, we must clearly articulate our unique contribution to health care and be empowered to unequivocally share our impact as we develop and disseminate nursing knowledge and science. I believe perioperative nurses lead the way in safety, and this special focus issue highlights a few examples of how you can impact staff safety in meaningful ways. This issue of the AORN Journal contains three feature articles on the topic of staff safety. The cornerstone of this special focus issue is the article, “Just culture: the foundation of staff safety in the perioperative environment.”1 This article describes what just culture is and is not, explains why just culture is foundational to staff safety, and provides the building blocks for how to establish a just culture in your work setting. This article also discusses who is responsible for just culture (everyone) and when to advocate for safety (always). For those organizations that have a well-developed just culture, the article reinforces the fundamental tenets of a just culture and promotes self-reflection to continue to cultivate and nurture a just culture in your organization. “The effects of flow disruptions on RN circulators”2 describes the uniqueness of the perioperative setting and the complexity of care delivered in it and the connection of situational awareness and staff safety. The article explores factors that contribute to the risk for staff member injury and thoroughly examines how flow disruptions affect staff safety. Recognizing flow disruptions and how they affect staff members empowers perioperative nurses to have an increased awareness to react and respond to safety threats. The final article, “Ergonomic challenges in the perioperative setting,”3 explores the unique physical demands of working in the perioperative environment and analyzes ergonomic risk factors that affect the health and safety of perioperative team members. The article includes recommendations for optimizing perioperative nurses’ physical health and safety. Being a perioperative nurse is a physically demanding job, and it is important that we have safety measures in place to eliminate injury. The articles in this special focus issue cover just the tip of the iceberg in terms of perioperative staff safety topics that need to be explored. I would like to highlight a few additional topics that are not included in this special focus issue but are important perioperative staff safety topics: self-care, The United States Pharmacopeial Convention’s USP <800>, workplace and lateral violence, smoke hazards, tripping hazards, bloodborne pathogens and other exposures (eg, radiation), weight of instrument trays, and coronavirus disease 2019 (COVID-19). My hope is that as a perioperative nurse, you prioritize safety for yourself and your team. Allow yourself to be actively engaged by “putting your oxygen mask on first” as you deliver exceptional patient care to surgical patients. If you see something unsafe, you are empowered to not only say something, but to do something about it. As perioperative nurses, you are critical to promoting and embracing safety in your organization. Jennifer L. Fencl, DNP, RN, CNOR, CNS, is the executive director of nursing practice and education at Cone Health, Greensboro, NC. Dr Fencl has no declared affiliation that could be perceived as posing a potential conflict of interest in the publication of this article.

Is Biopharma Ready for the Standard Wars?

This symposium contribution sheds new light on Momenta v. Amphastar, a case in which issues relating to standardization and patent disclosure that have previously been observed in the semiconductor, computing, and telecommunications sectors found their way into a dispute between two biosimilar manufacturers. One such manufacturer, Momenta, participated in the development of a standard for testing the purity of generic enoxaparin under the auspices of the United States Pharmacopeial Convention but failed to disclose that it had applied for a patent on the testing method. When Momenta later sued Amphastar for patent infringement by using the method in accordance with the FDA’s approval of its own generic version of enoxaparin, Amphastar raised waiver and equitable estoppel as defenses, then brought antitrust claims against Momenta and its distribution partner Sandoz. Amphastar prevailed at the district court, obtaining a ruling that Momenta’s patent was unenforceable. This case demonstrates that issues surrounding the acquisition and disclosure of patents on standardized technologies have more salience in the biopharma sector than commonly believed. As such, standards organizations operating in this sector should ensure that their policies and procedures are robust enough to delineate clearly the obligations of participants with respect to patents covering standardized technologies, and organizations that participate in biopharma standards-development should heed the valuable lessons offered by more than three decades of litigation and policy making in the technology sector.

Preparation of Nifedipine Push-Pull Osmotic Pump Tablets

This study aims to investigate the influence of the formulation factors on the drug release kinetics, thereby selecting the compositions of extended-release nifedipine tablet based on the similarity coefficient f2 obtained when compared with Adalat LA tablet. The formulation factors such as: molecular weight of the polyethylene oxide (PEO) and osmotic agent amount in drug layer and push layer, semi permeable membrane thickness (estimated by coating weight gain), orifice size, type of plasticizers and ratios of coating polymer to plasticizer in semipermeable membrane were evaluated. It was found that developed tablets were able to deliver nifedipine in an approximate zero-order manner up to 20 hours and drug release profile of developed tablets was similar to that from Adalat LA tablets. The developed tablet contained: PEO N10, PEO 303 in drug layer and push layer, respectively; percentages of osmotic agent in drug layer and push layer were 10% and 30%, respectively; weight gain of semipermeable coating was 12%; and orifice size was 0.8 mm.&#x0D; Keywords&#x0D; Nifedipine, GPKD, push-pull osmotic pump, PEO, Tlag.&#x0D; References&#x0D; [1] Vietnamese National Drug Formulary Council, Nifedipine, Vietnamese National Drug Formulary, 2nd edition, Medical Publising House, Hanoi, 2018, pp. 1056-1058 (in Vietnamese).[2] A. Nokhodchi, M.N. Momin, J. Shokri, et al., Factors affecting the release of nifedipine from a swellable elementary osmotic pump, Drug Delivery, 15 (1) (2008) 43-48. https://doi.org/10.1080/10717540701829028[3] R.K. Verma, D.M. Krishna, S. Garg, Formulation aspects in the development of osmotically controlled oral drug delivery systems, Journal of controlled release 79 (1-3) (2002) 7-27. https://doi.org/10.1016/s0168-3659(01)00550-8.[4] The United States Pharmacopeial Convention, Nifedipine Extended-Release Tablets, The United States Pharmacopeia, 41st edition, United Book Press, Baltimore, 2018, pp. 2938 - 2944.[5] V. Malaterre, J. Ogorka, N. Loggia, et al., Approach to design push–pull osmotic pumps, International Journal of Pharmaceutics 376 (1–2) (2009) 56-62. http://dx.doi.org/10.1016/j.ijpharm.2009.04.015.[6] S. Missaghi, P. Patel P, Farrell T. P., et al., Investigation of critical core formulation and process parameters for osmotic pump oral drug delivery, AAPS PharmSciTech 15 (1) (2014) 149-160. http://doi.org/10.1208/s12249-013-0040-4.[7] V. Malaterre, H. Metz, J. Ogorka , et al., Benchtop-magnetic resonance imaging (BT-MRI) characterization of push-pull osmotic controlled release systems, J Control Release 133 (1) (2009) 31-36. http://doi.org/10.1016/j.jconrel.2008.09.007.[8] Z. Zhang, W. Li, S. Nie, et al., Overcome side identification in PPOP by making orifices on both layers, International journal of pharmaceutics 371 (1-2) (2009) 1-7. http://dx.doi.org/10.1016/j.ijpharm.2008.12.006[9] C. Wu, Z. Zhao, Y. Zhao, et al., Preparation of a push–pull osmotic pump of felodipine solubilized by mesoporous silica nanoparticles with a core–shell structure, International Journal of Pharmaceutics,475 (1-2) (2014) 298 - 305 . http://dx.doi.org/10.1016/j.ijpharm.2014.08.033.[10] V. Patel, A. Chudasama, M. Nivsarkar, et al., Push-pull osmotic pump for zero order delivery of lithium carbonate: Development and in vitro characterization, Pharmaceutical development and technology, 17 (3) (2012) 375-382. http://doi.org/10.3109/10837450.2010.542577.[11] C.N. Patra, S. Swain, J. Sruti, et al., Osmotic drug delivery systems: Basics and design approaches, Recent Patents on Drug Delivery &amp; Formulation 7(2) (2013) 1 - 12. http://doi.org/10.2174/1872211311307020007.&#x0D; &#x0D;

More comprehensive standards for monitoring glycosylation

Biologics manufacturers must continually monitor the attachment of carbohydrates, called glycans, to their products, because any variability can impact safety and efficacy. To help the industry meet this challenge, the United States Pharmacopeial Convention (USP) offers glycan reference standards and validated methods for glycoprofiling using high-performance liquid chromatography (HPLC). The industry has recently adopted more advanced technologies for glycan analysis, including ultra-high performance liquid chromatography (UHPLC) and mass spectrometry. In this study, we confirm that USP's glycan reference standards are compatible with UHPLC by demonstrating comparable peak separation and glycan identification to HPLC methods. The improved resolving power and shorter run-times of UHPLC also allowed us to identify many of the minor glycan components present in USP's glycan reference standards. These more comprehensively characterized glycan reference standards will enable manufacturers to assess the micro-heterogeneity that can negatively impact the safety and efficacy of biological products.

A Protocol for the Safe Use of Hazardous Drugs in the OR.

Hazardous drug (HD) use in the perioperative environment poses unique challenges and risks for exposure that can have adverse consequences for perioperative personnel. The United States Pharmacopeial Convention has implemented new standards to address the safe handling and administration of HDs by health care workers. To comply with these standards and minimize perioperative personnel's occupational exposure to HDs, a multidisciplinary team at an academic medical center in Boston that was performing an increased number and variety of operative and other invasive procedures using antineoplastic agents updated their protocol for the safe use of HDs in the OR. This article discusses HDs and the risks they pose to health care workers and outlines the new HD safety protocol for the OR that was part of a performance improvement plan to ensure compliance with new standards and staff member safety in the perioperative setting.

Powder X-ray diffraction of fluorometholone, C22H29FO4

Commercial fluorometholone, CAS #426-13-1, crystallizes in the monoclinic space group P21 (#4) with a = 6.40648(2), b = 13.43260(5), c = 11.00060(8) Å, β = 92.8203(5)°, V = 945.517(5) Å3, and Z = 2. A reduced cell search in the Cambridge Structural Database yielded one previous structure determination, using single-crystal data at 292 K. In this work, the sample was ordered from the United States Pharmacopeial Convention (Lot # R032K0) and analyzed as-received. The room temperature (295 K) crystal structure was refined using synchrotron (λ = 0.412826 Å) powder diffraction data and optimized using density functional theory (DFT) techniques. Hydrogen positions were included as a part of the structure and were re-calculated during the refinement. The diffraction data were collected on beamline 11-BM at the Advanced Photon Source, Argonne National Laboratory, and the powder X-ray diffraction pattern of the compound has been submitted to ICDD® for inclusion in the Powder Diffraction File™. The agreement of the Rietveld-refined and DFT-optimized structures is excellent; the root-mean-square Cartesian displacement is 0.060 Å. In addition to the O–H⋯O hydrogen bonds observed by Park et al. (Park, Y. J., Lee, M. Y., and Cho, S. I. (1992). “Fluorometholone,” J. Korean Chem. Soc. 36, 812–817), C–H⋯O hydrogen bonds contribute to the crystal energy.

Powder X-ray diffraction of trimethoprim Form I, C14H18N4O3

Trimethoprim crystallizes in the triclinic space group P-1 (#2) with a = 10.5085(3), b = 10.5417(2), c = 8.05869(13) Å, α = 101.23371(21), β = 112.1787(3), γ = 112.6321(4)°, V = 743.729 Å3, and Z = 2. A reduced cell search in the Cambridge Structural Database yielded three previous structure determinations, using data collected at 100 K, 173 K, and room temperature. In this work, the sample was ordered from the United States Pharmacopeial Convention (USP) and analyzed as-received. The room temperature (295 K) crystal structure was refined using synchrotron (λ = 0.412826 Å) powder diffraction data and optimized using density functional theory techniques. We found similar hydrogen bonding patterns with the previous determinations. In addition, we identified two C–H⋯O hydrogen bonds, which also contribute to the crystal energy. When comparing the previously reported trimethoprim structure determinations, the unit cell length lattice parameters were found to contract at lower temperatures, particularly 100 K. All structures show reasonable agreement, with unit cell length differences ranging between 0.05 and 0.15 Å. The diffraction data for this study were collected on beamline 11-BM at the Advanced Photon Source, and the powder X-ray diffraction pattern of the compound has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®).

Powder X-ray diffraction of flucytosine, C4H4FN3O

Flucytosine, CAS #2022-85-7, crystallizes in the tetragonal space group P41212 (#94) with a = 6.643768(27), c = 23.89009(10) Å, V = 1054.500(7) Å3, and Z = 8. In this work, the sample was obtained from the United States Pharmacopeial Convention (USP) Lot #R03100 and analyzed as-received. The room temperature (295 K) crystal structure was refined using synchrotron (λ = 0.412826 Å) powder diffraction data and optimized using the density functional theory (DFT). When looking down the a-axis, the crystal structure consists of multiple ribbon-like structures stacked into columns. The powder X-ray diffraction pattern of the compound has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®). The agreement of the Rietveld-refined and DFT-optimized structures is good, with the largest difference in the external amine group with an overall root mean displacement of 0.056 Å. There is also evidence of unit cell expansion at higher temperatures, as the volume of the unit cell at 298 K was 1.6–1.9% greater than the two unit cells obtained at 150 K. A N–H⋯O hydrogen bond exists in the inter-ribbon region between the flucytosine molecules, resulting in a 3D hydrogen bond network.

Powder X-ray diffraction of capecitabine, C15H22FN3O6

Capecitabine (Xeloda) is a chemotherapy drug used to treat breast, gastric, and colorectal cancers. Commercial capecitabine crystallizes in the orthorhombic space group P212121 (#19) with a = 5.20587(3), b = 9.52324(4), c = 34.79574(21) Å, V = 1725.062(12) Å3, and Z = 4. A reduced cell search in the Cambridge Structural Database (Groom C. R., Bruno, I. J., Lightfoot, M. P., and Ward, S. C. (2016) Crystallogr. Sect. B: Struct. Sci., Cryst. Eng. Mater.72, 171–179) yielded three previous structure determinations (Rohlicek, J., Husak, M., Gavenda, A., Jegorov, A., Kratochvil, B., and Fitch, A. (2016). Acta Cryst. Sect. E: Crystallgr. Commun.72, 879–880, BOVDUM; Malińska, M., Krzeczyński, P., Czerniec-Michalik, E., Trzcińska, K., Cmoch, P., Kutner, A., and Woźniak, K. (2014). J. Pharm. Sci.103, 587–593, BOVDUM01 and BOVDUM02), using synchrotron powder data and later single crystal data at two temperatures. In this work, the sample was ordered from United States Pharmacopeial Convention (lot # G0J205), and analyzed as-received. The room temperature (295 K) crystal structure was refined using synchrotron (λ = 0.413914 Å) powder diffraction data, density functional theory (DFT), and Rietveld refinement techniques. Hydrogen positions were included as part of the structure, and were re-calculated during the refinement. The diffraction data were collected on a beamline 11-BM at the Advanced Photon Source, Argonne National Laboratory and the powder X-ray diffraction pattern of the compound is provided. The agreement of the Rietveld-refined and DFT-optimized structures is poorest in the pentyl side chain, consistent with the disorder observed previously.

Your Patient's Expired Naloxone Might Still Be Good

Medications are intended to be stored based on United States Pharmacopeial Convention (USP) standards, which include a desired temperature range and an

Selective laser fiber welding on woven polymer fabrics for biomedical applications

Localized cartilage damage is a common problem for younger patients. This can heal, but often results in a painful condition that requires intervention. A welded-woven three-dimensional polymer fabric has been suggested as a suitable cartilage replacement because such materials closely match the mechanical properties of cartilage. However, such materials fare poorly when evaluated with respect to wear. A microscopic investigation of wear mechanisms showed that it is critical that the fibers not deflect laterally under a normal load. This observation led to the use of a new process for selective laser welding of the surface layers of three-dimensional fabrics in order to improve their wear resistance. Experimental evaluations were made in a pin-on-disc arrangement with a biomimetic loading. All materials used in the studies have previously been used in orthopedic devices or meet the requirements for United States Pharmacopeial Convention (USP) Class VI biocompatibility approval. The wear rates were significantly reduced and the lifespan of the fabrics was markedly improved due to surface welding, making this a viable option for cartilage replacement in vivo.

The Value of U.S. Pharmacopeial Standards: A Review of the Literature

While there are many standard-setting health care organizations, the United States Pharmacopeial Convention's (USP) role includes the creation of documentary and physical standards for therapeutics, including chemical drugs, excipients, and biologics. Despite the ubiquity of these standards, little work has been carried out to characterize and quantify their value. We reviewed the peer-reviewed and gray literature relevant to such evaluations. The review yielded 36 articles, focused variously on accreditation and other standards in health care, the broad impact of pharmacopeial standards and evaluations of specific USP standards. We did not find any study quantifying the impact of USP or other pharmacopeial standards, but many reports have been published that suggest the utility of USP standards to drug development, quality assurance, and public health. Frequently cited areas of impact include equitably advancing the analytical capabilities of manufacturers; enabling the creation of legally enforceable naming conventions; detecting mislabeled and substandard drugs in the marketplace, especially in the context of increased globalization of drug markets; and facilitating the harmonization of diverse international drug quality standards. Our insights provide opportunities for empiric assessments of the effects of USP standards on important outcomes including their promotion of efficient drug development, market competition, drug quality, and patient safety.

In Memoriam: Darrell R. Abernethy 1949–2017

In Memoriam: Darrell R. Abernethy 1949–2017

In Memoriam: Darrell R. Abernethy, 1949–2017

In Memoriam: Darrell R. Abernethy, 1949–2017

Holistic Considerations in Optimizing a Sterile Product Package to Ensure Container Closure Integrity.

A new major chapter dealing with container closure integrity was released by the United States Pharmacopeial Convention. Chapter <1207> provides a significant amount of education and guidance concerning test methodologies to prove that a system is integral and safe for use. The test method used is only one of the major considerations in approaching the challenge of proving an integral system. This paper takes a holistic review of all the major considerations needed in qualifying a new vial system for container closure integrity. There is substantial interplay among many aspects in the process of sealing a vial. This review helps to define major risks that need to be considered and mitigated and reinforces the need to understand the maximum allowable leakage limit that is acceptable for a specific drug application. A typical risk-based approach considers materials, test methods, process, people, environment, and equipment. Each of these aspects is considered in some detail along with a recommended process flow for building a best practice, science-based approach. This approach will inform decision making for evaluating the correct combination of components and assuring they are assembled and tested in an appropriate manner. This work, once completed, can be the basis for a vial system platform or specific drug application qualification.LAY ABSTRACT: Container closure integrity is a fundamental requirement of every sterile drug package. With recent upgrading of compendia standards and guidance around this issue, there is an opportunity to better define a best practice approach to a complicated subject. It is important to recognize that there is substantial interplay among the components of the system, the process of assembly, and the test methods that are used. This paper takes a holistic approach to discussing these issues and identifying the risks that must be considered in assuring an integral container over the shelf life of a drug product.

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer–Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible.

Long-Term Care: Safe Drug Handling of Oral Chemotherapy.

Many oral chemotherapy agents have been approved over the last 15 years and are displacing or augmenting parenteral chemotherapy. As 8,000 Baby Boomers turn 65 years of age every day, more elders will migrate to long-term care and assisted living facilities, and consultant pharmacists may need to manage chemotherapy for the first time. Though many therapeutic classes of oral drugs are hazardous, the majority of oral chemotherapy agents are hazardous by virtue of their mechanisms of action. Previous hazardous drug-handling recommendations from the Occupational Safety and Health Administration, the National Institute of Occupational Safety and Health, the American Society of Health-System Pharmacists, the American Society of Clinical Oncology, the Hematology/Oncology Pharmacy Association, and the Oncology Nursing Society have matured into new standards from the United States Pharmacopeial Convention (USP), Chapter <800>, "Hazardous Drugs-Handling in Health Care Settings." These standards provide a comprehensive approach for safe drug handling across all health care settings and underscore the need for consultant pharmacist involvement in nursing and assisted living facilities.