Intraperitoneal lidocaine instillation during abdominal hysterectomy: A systematic review and meta-analysis of randomized placebo-controlled trials.

AIM: To perform a systematic review and meta-analysis of all randomized placebo-controlled trials (RCTs) that inspected the analgesic benefits of intraperitoneal lidocaine instillation among patients undergoing abdominal hysterectomy. METHODS: Five electronic databases were inspected from till August 5, 2021. The eligible RCTs were evaluated for risk of bias. The pooled endpoints were summarized as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI). RESULTS: Five RCTs met the inclusion criteria comprising 263 patients (119 and 117 patients were allocated to lidocaine and control group, respectively). The included RCTs demonstrated a low risk of bias. The postoperative pain score at rest was significantly lower in favor of the lidocaine group (MD=-1.01, 95% CI [-1.20, -0.81], p<0.001), and subgroup analysis demonstrated the same at 2, 4, 8, 12, 24, and 48 h postoperatively. Moreover, the postoperative pain score at moving was significantly lower in favor of the lidocaine group (MD=-0.67, 95% CI [-1.01, -0.33], p<0.001), and subgroup analysis demonstrated the same at 2 and 48 h postoperatively. The postoperative morphine consumption during 0-24 h was significantly lower in favor of the lidocaine group (n = 5 RCTs, MD=-7.29 mg, 95% CI [-13.22, -1.37], p = 0.02). The rate of postoperative vomiting was significantly lower in favor of the lidocaine group (n = 4 RCTs, RR=0.54, 95% CI [0.31, 0.95], p = 0.03). CONCLUSION: Among patients undergoing abdominal hysterectomy, intraperitoneal lidocaine instillation is feasible, cheap, safe, and associates with effective analgesia in terms of reduced postoperative pain score and morphine consumption.

Identification and quantification of glucose degradation products in heat-sterilized glucose solutions for parenteral use by thin-layer chromatography.

During heat sterilization of glucose solutions, a variety of glucose degradation products (GDPs) may be formed. GDPs can cause cytotoxic effects after parenteral administration of these solutions. The aim of the current study therefore was to develop a simple and quick high-performance thin-layer chromatography (HPTLC) method by which the major GDPs can be identified and (summarily) quantified in glucose solutions for parenteral administration. All GDPs were derivatized with o-phenylenediamine (OPD). The resulting GDP derivatives (quinoxalines) were applied to an HPTLC plate. After 20 minutes of chamber saturation with the solvent, the HPTLC plate was developed in a mixture of 1,4-dioxane-toluene-glacial acetic acid (49:49:2, v/v/v), treated with thymol-sulfuric acid spray reagent, and heated at 130°C for 10 minutes. Finally, the GDPs were quantified by using a TLC scanner. For validation, the identities of the quinoxaline derivatives were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Glyoxal (GO)/methylglyoxal (MGO) and 3-deoxyglucosone (3-DG)/3-deoxygalactosone (3-DGal) could be identified and quantified in pairs, glucosone (2-KDG), 5-hydroxymethylfurfural (5-HMF), and 3,4-dideoxyglucosone-3-ene (3,4-DGE) each individually. For 2-KDG, the linearity of the method was demonstrated in the range of 1-50 µg/mL, for 5-HMF and 3,4-DGE 1-75 µg/mL, for GO/MGO 2-150 µg/mL, and for 3-DG/3-DGal 10-150 µg/mL. All GDPs achieved a limit of detection (LOD) of 2 µg/mL or less and a limit of quantification (LOQ) of 10 µg/mL or less. R2 was 0.982 for 3.4-DGE, 0.997 for 5-HMF, and 0.999 for 2-KDG, 3-DG/3-DGal, and GO/MGO. The intraday precision was between 0.4 and 14.2% and the accuracy, reported as % recovery, between 86.4 and 112.7%. The proposed HPTLC method appears to be an inexpensive, fast, and sufficiently sensitive approach for routine quantitative analysis of GDPs in heat-sterilized glucose solutions.

A standardized glucose-insulin-potassium infusion protocol in surgical patients: Use of real clinical data from a clinical data warehouse.

AIMS: We evaluated the clinical usefulness of a new unified glucose-insulin-potassium (GIK) regimen in a general surgical department. METHODS: Surgical patients treated under the previous diverse GIK regimens (September 2016 to August 2017) and the new unified GIK regimen (September 2017 to August 2018) were identified in records of the Clinical Data Warehouse of Seoul National University Bundang Hospital. Serial and area under the curve (AUC) glucose levels, and percentages of time within the target glucose levels were compared in propensity score matched patients in the diverse GIK regimen and in the unified GIK regimen (n = 227 in each group). RESULTS: The AUC of glucose at 6 h and 12 h was lower under the unified GIK regimen than the diverse GIK regimen. The percentage of target glucose levels was higher in the unified GIK regimen compared to the diverse GIK regimen (81.5% vs. 75.0%, P = 0.026), but the occurrence of hypoglycaemia did not differ significantly between groups. CONCLUSIONS: The unified GIK regimen was more effective than the diverse GIK regimen for glycaemic control and did not increase the number of patients developing hypoglycaemia. This validated written GIK regimen can be safely used in a general surgical department.

Home intravenous antibiotherapy and the proper use of elastomeric pumps: Systematic review of the literature and proposals for improved use.

Over several decades, the economic situation and consideration of patient quality of life have been responsible for increased outpatient treatment. It is in this context that outpatient antimicrobial treatment (OPAT) has rapidly developed. The availability of elastomeric infusion pumps has permitted prolonged or continuous antibiotic administration by dint of a mechanical device necessitating neither gravity nor a source of electricity. In numerous situations, its utilization optimizes administration of time-dependent antibiotics while freeing the patient from the constraints associated with infusion by gravity, volumetric pump or electrical syringe pump and, more often than not, limiting the number of nurse interventions to one or two a day. That much said, the installation of these pumps, which is not systematically justified, entails markedly increased OPAT costs and is liable to expose the patient to a risk of therapeutic failure or adverse effects due to the instability of the molecules utilized in a non-controlled environment, instability that necessitates close monitoring of their use. More precisely, a prescriber must take into consideration the stability parameters of each molecule (infusion duration, concentration following dilution, nature of the diluent and pump temperature). The objective of this work is to evaluate the different means of utilization of elastomeric infusion pumps in intravenous antibiotic administration outside of hospital. Following a review of the literature, we will present a tool for optimized antibiotic prescription, in a town setting by means of an infusion device.

Systematic review of stability data pertaining to selected antibiotics used for extended infusions in outpatient parenteral antimicrobial therapy (OPAT) at standard room temperature and in warmer climates.

Aim: To determine if there are sufficient stability data to confirm appropriate prescribing of antibiotics commonly used in outpatient parenteral antimicrobial therapy (OPAT) in warmer climates. Data sources: Four databases were systematically searched using the terms 'beta-lactams', or 'antibiotics', or 'anti-bacterial agents' and 'drug stability' or drug storage' for studies specific to drug stability published between 1966 and February 2018. Study selection: The search strategy initially identified 2879 potential articles. After title and abstract review, the full-texts of 137 potential articles were assessed, with 46 articles matching the inclusion and exclusion criteria included in this review. Results: A large volume of stability data is available for the selected drugs. Stability data at temperatures higher than 25°C were available for several of the medications, however few drugs demonstrated stability in warmer climates of 34°C or higher. Only buffered benzylpenicillin, cefoxitin and buffered flucloxacillin were found to have stability data supporting OPAT in warmer climates. Sequential data, profiling the drug for an extended period in solution under refrigeration prior to the run-out period at the higher temperatures, are also lacking. Limitations: This study was limited by including only peer reviewed articles. There may be further grey literature supporting the stability of some of the drugs mentioned. Conclusion: There are insufficient stability data of antibiotic use in warmer climates. Studies to verify the stability and appropriate use of many antibiotics used in OPAT at standard room temperature and in warmer climates are urgently required. Several drugs in current use in the OPAT settings are lacking stability data. Implications: Further research in this field is needed to develop structured evidence-based guidelines. Results of this review should be further compared with observed patient outcomes in current clinical practice.

Subvisible Particulate Contamination in Cell Therapy Products-Can We Distinguish?

Cell therapy products represent an exciting new class of medicinal products, which must be parenterally administered. Thus, compliance with parenteral preparation guidelines is required. One requirement for parenteral products is the characterization of particle contaminations. As cell-based products are turbid suspensions, containing particles, the cells, characterization and control of foreign particle impurities remain a challenge. Within this study, we evaluated a flow imaging microscopy method for the detection and characterization of subvisible particle contaminations in cell-based products. We found that flow imaging microscopy is a potential method where subvisible particle contaminations can be differentiated from the cells in cell therapy products.

Implications of parenteral chemotherapy dose standardisation in a tertiary oncology centre.

BACKGROUND: Dose banding parenteral chemotherapy has the potential to optimise aseptic unit capacity and reduce drug expenditure without compromising the service provided. METHODS: Dose banding tables from NHS England were implemented into the electronic chemotherapy prescribing system. Compliance to the dose bands was analysed and submitted quarterly. Analysis of drug expenditure, drug use and cost per milligram data was also collected. RESULTS: Expenditure on the 17 drugs identified in the 2016/17 dose standardisation CQUIN reduced by approximately £100,000 per month over the CQUIN despite an increase in the number of prescribed doses of these drugs. At the beginning of the year, the percentage of work compounded in house was 60%, which was reduced to 51% of total workload at the end of the year due to outsourcing commonly prescribed doses from commercial pharmaceutical aseptic manufacturers. CONCLUSION: Dose banding parenteral chemotherapy is an efficient cost-saving strategy which also can help to increase the capacity of the aseptic unit.

Quality of outpatient parenteral antimicrobial therapy (OPAT) care from the patient's perspective: a qualitative study.

OBJECTIVES: Current outpatient parenteral antimicrobial therapy (OPAT) guidelines recommend delivering patient-centred care. However, little is known about what patients define as good quality of OPAT care and what their needs and preferences are.The aim of this qualitative study is to explore the patients' perspective on high-quality care, and to explore what patient-centred care means to adult OPAT patients. DESIGN AND SETTING: This is an explorative, descriptive study using qualitative methods. We conducted focus group interviews with 16 adult patients (5 female, 11 male) from 3 different hospitals, who received OPAT and 2 individual semistructured interviews with their informal caregivers in the Netherlands. We used purposive sampling to ensure diversity of participants. We used the eight Picker principles of patient-centredness to guide data collection and analysis. RESULTS: Participants reported several elements considered as important for patient-centred OPAT care, like patient involvement in the decision-making process, a responsible OPAT lead, intensive collaboration between all disciplines involved, information provision and adherence to hygiene guidelines. Two central dimensions emerged as essential constituents of patient-centred OPAT care: freedom and safety. Both are heavily influenced by the behaviours of healthcare professionals and by organisational aspects beyond the direct influence of these professionals. CONCLUSION: This study provides insights into the needs and preferences of adult patients who receive OPAT care. Future interventions directed at the improvement of patient-centredness of OPAT care should focus on elements that enhance patients' feelings of freedom and safety.

Migration of plasticizers from poly(vinyl chloride) and multilayer infusion bags using selective extraction and GC-MS.

Flexible poly(vinyl chloride) (PVC) is widely used in the pharmaceutical industry for the manufacture of medical devices (tubes, probes, bags, primary packaging, etc.). The objective of the present study was to develop a procedure to evaluate the migration potential of nine plastic additives in aqueous infusion bags (NaCl 0.9% and glucose 5%): five phthalates, one adipate, two alkylphenols, and benzophenone. Two types of materials were analyzed: (i) new and outdated plasticized PVC (containing 40% of diethylhexyl phthalate DEHP); and (ii) tri-laminate polyethylene-polyamide-polypropylene, a multilayer material presumably exempt from DEHP. In addition, we evaluated the migration of plasticizers from PVC raw materials (film and grain) under controlled conditions to compare the migration levels according to Regulation 2011/10. Solid phase extraction and liquid-liquid extraction with gas-chromatography coupled to mass spectrometry were used in all tests. The migration of DEHP in PVC grain exceeded the maximum regulated level of 5000 µg/kg, whereas the levels were much lower in films. In new PVC bags, DEHP was the only compound detected at 4.31 ±â€¯0.5 µg/L in NaCl 0.9% and 4.29 ±â€¯0.25 µg/L in glucose 5% serums, whereas the levels increased 10 times in three-year shelf-life bags. In multilayer bags, DEHP was not found but instead, two plasticizers were detected namely dibuthylphthalate (DBP) and diethylphthalate (DEP) at 0.7 ±â€¯0.1 µg/L and 4.14 ±â€¯0.6 µg/L, respectively. These plasticizers are not mentioned as additives allowed in materials intended for parenteral use (European Pharmacopoeia 8.0, 3.1.5. and 3.1.6.). Caprolactam was tentatively identified and could have stemmed from the polyamide of the multilayer composite. The levels of phthalates remained low but not negligible and might constitute a risk to public health in the case of reiterative infusions.

Simulated Leaching (Migration) Study for a Model Container-Closure System Applicable to Parenteral and Ophthalmic Drug Products.

A simulating leaching (migration) study was performed on a model container-closure system relevant to parenteral and ophthalmic drug products. This container-closure system consisted of a linear low-density polyethylene bottle (primary container), a polypropylene cap and an elastomeric cap liner (closure), an adhesive label (labeling), and a foil overpouch (secondary container). The bottles were filled with simulating solvents (aqueous salt/acid mixture at pH 2.5, aqueous buffer at pH 9.5, and 1/1 v/v isopropanol/water), a label was affixed to the filled and capped bottles, the filled bottles were placed into the foil overpouch, and the filled and pouched units were stored either upright or inverted for up to 6 months at 40 °C. After storage, the leaching solutions were tested for leached substances using multiple complementary analytical techniques to address volatile, semi-volatile, and non-volatile organic and inorganic extractables as potential leachables.The leaching data generated supported several conclusions, including that (1) the extractables (leachables) profile revealed by a simulating leaching study can qualitatively be correlated with compositional information for materials of construction, (2) the chemical nature of both the extracting medium and the individual extractables (leachables) can markedly affect the resulting profile, and (3) while direct contact between a drug product and a system's material of construction may exacerbate the leaching of substances from that material by the drug product, direct contact is not a prerequisite for migration and leaching to occur.LAY ABSTRACT: The migration of container-related extractables from a model pharmaceutical container-closure system and into simulated drug product solutions was studied, focusing on circumstances relevant to parenteral and ophthalmic drug products. The model system was constructed specifically to address the migration of extractables from labels applied to the outside of the primary container. The study demonstrated that (1) the extractables that do migrate can be correlated to the composition of the materials used to construct the container-closure systems, (2) the extent of migration is affected by the chemical nature of the simulating solutions and the extractables themselves, and (3) even though labels may not be in direct contact with a contained solution, label-related extractables can accumulate as leachables in those solutions.

[Security of hospital infusion practices: From an a priori risk analysis to an improvement action plan]. / Sécurisation de la perfusion en milieu hospitalier : de l'analyse de risques a priori au plan d'action d'amélioration des pratiques.

OBJECTIVES: Infusion in care units, and all the more in intensive care units, is a complex process which can be the source of many risks for the patient. Under cover of an institutional approach for the improvement of the quality and safety of patient healthcare, a risk mapping infusion practices was performed. METHODS: The analysis was focused on intravenous infusion situations in adults, the a priori risk assessment methodology was applied and a multidisciplinary work group established. RESULTS: Forty-three risks were identified for the infusion process (prescription, preparation and administration). The risks' assessment and the existing means of control showed that 48% of them would have a highly critical patient security impact. Recommendations were developed for 20 risks considered to be most critical, to limit their occurrence and severity, and improve their control level. An institutional action plan was developed and validated in the Drug and Sterile Medical Devices Commission. CONCLUSION: This mapping allowed the realization of an exhaustive inventory of potential risks associated with the infusion. At the end of this work, multidisciplinary groups were set up to work on different themes and regular quarterly meetings were established to follow the progress of various projects. Risk mapping will be performed in pediatric and oncology unit where the risks associated with the handling of toxic products is omnipresent.

Best Practices in Alemtuzumab Administration: Practical Recommendations for Infusion in Patients With Multiple Sclerosis.

With the growing complexity of multiple sclerosis (MS) care, nursing professionals have increasing responsibility in managing clinical disease and treatment. Nursing professionals and other health care providers play important roles in educating patients about disease-modifying therapy options, the course of therapy, and managing potential adverse effects. A panel of nursing and MS experts was convened and used a modified Delphi method to reach consensus on best-practice recommendations for alemtuzumab infusion in MS patients. This valuable clinical resource provides a practical guide for clinicians to optimize patient education and implement strategies for infusion-associated reaction prophylaxis and management when administering alemtuzumab.

Drug administration via enteral feeding tube in residential care facilities for individuals with intellectual disability: A focus group study on guideline implementation.

People with profound intellectual disabilities often receive medication through enteral feeding tube (EFT). In a previous study, we found that current guidelines concerning medication preparation and administration through EFT are often not followed in residential care facilities (RCFs) for individuals with intellectual disabilities. The present qualitative study aimed to identify barriers and facilitators experienced by RCF staff members to following guidelines on medication administration via EFT, by conducting focus group interviews. Time constraints, lack of knowledge, lack of clear administration instructions, lack of necessary materials, and limited gastric fluid tolerance in certain residents were identified as barriers to following guidelines. Other influencing factors were the number of staff members, residents, and medications; habits; and the residents' comfort and well-being. To optimize care for this vulnerable patient population with EFT, an intervention can be set up focusing on improving staff members' medication-related knowledge and providing clear administration instructions and the necessary materials.

Filtration of Glass Delamination Particles with West Pharmaceutical Vial Adapters.

UNLABELLED: One major current challenge facing companies producing injectable drugs contained in glass vials is the phenomenon of delamination that results in drug contamination. Particulate contamination of parenteral fluids is a fact of life. Particulate infusion is unlikely to cause immediate or severe signs and symptoms, but adverse effects, tissue damage, and loss of function are likely in the long term. Since 2010, recalls due to glass delamination have increased, and recently the U.S. Food and Drug Administration exercised temporary regulatory flexibility by allowing filtration as means of removing glass particles. The vial adapter is a needle-free product from West Pharmaceuticals Services that provides a simple and cost-effective solution for the safe and rapid transfer reconstitution of drugs between vials and syringes. One variant of the vial adapter is integrated with a filter to address various types of particles. In the present study, the performance of the filter-integrated vial adapter is evaluated with respect to glass delamination particles. Silica particles of 0.5-10 µm are used to emulate glass delamination particles. High-filtration efficiency is demonstrated according to the severest criteria stated by the British Pharmacopoeia that allows up to 100 particles smaller than 5 µm for every 1 mL liquid of a large-volume parenteral. The study was conducted using environmental scanning electron microscopy and statistical analysis. LAY ABSTRACT: One major current challenge facing companies producing injectable drugs contained in glass vials is the phenomenon of delamination that results in drug contamination. Glass delamination is defined as degradation of surface glass, as from a vial, that produces glass flakes. Contamination of injectable drugs due to glass delamination is a fact of life. Normally, this type of contamination does not involve immediate severe signs, but rather accumulative damage to tissues in the long run. Recently, the U.S. Food and Drug Administration allowed the filtration as means of removing particles. The vial adapter is a needle-free product from West Pharmaceuticals Services that provides a simple and cost-effective solution for the safe and rapid transfer reconstitution of drugs between vials and syringes. One variant of the vial adapter is integrated with a filter to address various types of particles. In the present study, the performance of the filter-integrated vial adapter is evaluated with respect to glass delamination particles. Silica particles of 0.5-10 µm are used to emulate glass delamination particles. High-filtration efficiency is demonstrated according to the severest criteria stated by the British Pharmacopoeia that allows up to 100 particles smaller than 5 µm for every 1 mL liquid of a large-volume parenteral. The study was conducted using environmental scanning electron microscopy and statistical analysis.

Particle contamination of parenteralia and in-line filtration of proteinaceous drugs.

Protein drug products play an important role in the treatment of severe diseases. However, due to the instability of these complex molecules, protein aggregates can form which can compromise drug safety and efficacy including immunogenic reactions. In-line filtration during the administration of these drugs can serve as a final safeguarding step to protect patients from risks associated with proteinaceous particles. A unique analysis of more than 300 marketed protein drug products revealed that already around 16% of all these products are filtered during preparation or administration. Further, the research revealed that no standardized filtration practice exists. Broad variances regarding filter membrane or pore size are found and sometimes no specifications are mentioned at all. The benefits as well as possible negative impacts of filtration like filter shedding, extractables or drug adsorption are critically assessed. Several proposals to improve the current filtration practice and to expand the number of in-line filtered protein drug products are made. The suggestions include the demand for the specific usage of one filter membrane type, the establishment of a filtration routine for unfiltered protein drugs and a statistical analysis between filtered and non-filtered products with similar formulations to identify possible differences in the immunogenicity rate.

[Parenteral administration medicines: recommendations of preparation, administration and stability]. / Medicamentos de administración parenteral: recomendaciones de preparación, administración y estabilidad.

OBJECTIVE: To develop recommendations for the preparation of parenteral drugs (MAP), to assess the transferability of their preparation, from nursing units in the hospital ward to the pharmacy service (SF). METHOD: A table of stabilities of parenteral drugs included in the pharmacotherapeutic guideline was developed using the american and spanish guidelines. Information about MAP was collected (method of preparation, support, maintenance, validity, administration specifications and packaging) by consulting product technical sheets, pharmaceutical industries, literature review and databases. RESULTS: After reviewing 209 drugs, a list of recommendations was developed. According to the data, MAP will be prepared as follows: 89 drugs will be prepared from SF, 62 drugs at nursing units because of its immediate administration requirement and 58 are already packed for its administration by the industry. Of these 62 drugs prepared a nursing units, 14 of them will be prepared in the following doses by the SF. Therefore, 48 drugs will be prepared at nursing units from the 209 parenteral drugs reviewed. CONCLUSIONS: A standardized method of preparation, storage, administration and validity of MAP was established by the SF. The preparation of MAP in the SF extends its shelf life, by considering physicochemical stability, level of risk and product vulnerability to microbiological contamination. The information provided will contribute to a reduction of errors associated with the preparation and administration of MAP.

Objetivo: Elaborar unas recomendaciones de preparacion de medicamentos de administracion parenteral (MAP) para valorar la posibilidad de transferir su preparacion, desde las unidades de enfermeria en planta de hospitalizacion al servicio de farmacia (SF). Método: Se procede a elaborar una tabla de estabilidades de los medicamentos incluidos en la guia farmacoterapeutica del Hospital, aplicando la Guia USP (Pharmaceutical compounding Sterile Preparations) y la Guia de de buenas practicas de preparacion de medicamentos en los servicios de farmacia hospitalaria. Se recopilo informacion sobre las MAP: metodo de preparacion, compatibilidad, conservacion, periodo de validez, modo de administracion y tipo de envase. Los datos se obtuvieron mediante consulta de las fichas tecnicas, laboratorios, revision bibliografica y otras bases de datos. Resultados: Tras revisar 209 farmacos se elaboro un listado de recomendaciones. Segun los datos obtenidos, las MAP se prepararan de la siguiente forma: 89 seran preparadas desde el SF, 62 en unidad de enfermeria en planta de hospitalizacion pues son medicamentos que requieren administracion inmediata y 58 ya van acondicionados para su administracion por la industria. De los 62 farmacos que se prepararan por enfermeria, en 14 de ellos las dosis siguientes se prepararan desde el SF. Por lo tanto de los 209 farmacos solo 48 se prepararan exclusivamente en la unidad de enfermeria. Conclusiones: Desde el SF se ha establecido un metodo normalizado de preparacion, conservacion, administracion y periodo de validez de MAP. La preparacion de MAP en SF ampliaria su tiempo de conservacion, al tener en cuenta la estabilidad fisicoquimica, el nivel de riesgo y la vulnerabilidad del preparado a la contaminacion microbiologica. La informacion aportada contribuira a una disminucion de errores asociados al proceso de preparacion y administracion de MAP.

In-vitro dissolution methods for controlled release parenterals and their applicability to drug-eluting stent testing.

OBJECTIVES: Dissolution testing is a powerful tool for the characterization of dosage form performance in vitro under standardized conditions. In spite of the increasing number of parenterally administered medicinal products, currently there are no compendial dissolution test methods designed especially for these types of dosage forms. In addition to classical drug delivery systems, drug/device combination products, such as drug-eluting stents, are being used increasingly. KEY FINDINGS: This review describes the current methods that are used most often for in-vitro dissolution testing of parenteral dosage forms, i.e. the 'sample and separate' methods, the 'dialysis' methods, and the 'flow-through' methods, with a special emphasis on whether these methods can be used for drug-eluting stent testing. In the light of current regulatory requirements and with the exploding costs of preclinical and clinical development, test systems that include biorelevant parameters and are predictive of in-vivo performance are increasingly important. Published attempts to take biorelevant conditions into consideration in the design of dissolution test apparatus developed for parenteral dosage forms, including a method that was designed to emulate the embedding and flow-conditions at the site of stent implantation, have been outlined in this review. SUMMARY: In spite of the large quantity of highly potent controlled release parenteral products marketed today, there is still a lack of suitable methods for in vitro dissolution testing for these dosage forms especially with regard to biorelevant testing conditions. For dosage forms implanted into tissues it seems of major importance to reproduce the transport forces which are predominant in vivo (diffusive versus convective) in the in-vitro experimental setup.

Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

OBJECTIVES: This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. KEY FINDINGS: Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. SUMMARY: Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable.