Physical Compatibility Between Intravenous Magnesium Sulfate and Potassium or Sodium Phosphate in a Pediatric Intensive Care Unit.

Objective:To evaluate the physical compatibility between intravenous magnesium sulfate and potassium and sodium phosphate, a common electrolyte intravenous supplementation in pediatric intensive care units. Study design: Magnesium sulfate was mixed separately with potassium phosphate and sodium phosphate at ratios of 1:1, 1:4, and 4:1. Binary mixtures were prepared, in triplicate and under sterile conditions, by permuting the order of addition. The undiluted pure drugs were used as controls for possible sequence effects. Visual changes, turbidity, and pH were assessed immediately after mixing (baseline) and at 4 and 24 hours. Two observers performed visual changes by naked-eye visual inspection in order to search visible haze, particulate matter, gas formation, or color change. Turbidity was measured by nephelometry and incompatibility was defined as an increase of ≥0.5 nephelometric turbidity units (NTU) from baseline. pH was measured using a portable pH meter and incompatibility was defined as a variation of >1 pH unit during the observation period. Results: None of the admixtures exhibited visual changes or significant variations in turbidity (increases of ≥0.5 in nephelometric turbidity units) or pH (changes of >1 unit) during the observation period and neither compared with baseline. Conclusion: In this study, no visual changes were observed, and turbidity and pH evaluated by instrumental methods remained within acceptable limits and showed no significant variations from baseline, therefore no physical incompatibility between magnesium sulfate and potassium or sodium phosphate was found.

Stability studies of ß-Amino- and ß-Hydroxy difluoromethyl ketones in rat serum and rat liver microsomes.

Although difluoromethyl ketones are used as tools in chemical biology and leads in drug discovery, the metabolic stability of these compounds is generally uncharacterized and must be inferred from in vivo pharmacological assays. In order to address this gap which impedes their wider use, we have synthesized and performed metabolic stability studies for thirty-nine ß-amino and ß-hydroxy difluoromethyl ketones. These investigations provide structure-stability relationships of the difluoromethyl ketones following incubation with rodent serum and liver microsomes.

Tacrolimus: Physicochemical stability challenges, analytical methods, and new formulations.

Tacrolimus, a potent immunosuppressant, is widely used in several formulations to treat organ rejection in transplant patients. However, its physicochemical stability poses significant challenges, including thermal instability, photostability issues, low solubility, and drug-excipient incompatibility. This review article focuses on the details of these challenges and discusses the analytical methods employed to study tacrolimus stability, such as thermal, spectroscopic, and chromatographic methods in different formulations. New formulations to enhance tacrolimus stability are explored, including lipid-based nanocarriers, polymers, and thin film freezing. Researchers and formulators can optimize tacrolimus formulations to improve efficacy and patient outcomes by understanding and addressing these stability challenges.

ICH M10 Bioanalytical Method Validation Guideline-1 year Later.

The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) adopted Guideline M10 entitled "Bioanalytical Method Validation and Study Sample Analysis" in May 2022. In October 2023, approximately one year after the adoption of the ICH M10 guideline, a "Hot Topic" session was held during the AAPS PharmSci 360 meeting to discuss the implementation of the guideline. The session focused on items the bioanalytical community felt were challenging to implement or ambiguous within the guideline. These topics included cross-validation, parallelism, comparative bioavailability studies, combination drug stability, endogenous analyte bioanalysis, and dilution QCs. In addition, the regulatory perspective on the guideline was presented. This report provides a summary of the Hot Topic session.

Zeolite-based nanoparticles drug delivery systems in modern pharmaceutical research and environmental remediation.

This review explores the potential of zeolite-based nanoparticles in modern pharmaceutical research, focusing on their role in advanced drug delivery systems. Zeolites, integrated into polymeric materials, offer precise drug delivery capabilities due to their unique structural features, biocompatibility, and controllable properties. Additionally, zeolites demonstrate environmental remediation potential through ion exchange processes. Synthetic zeolites, with modified release mechanisms, possess distinctive optical and electronic properties, expanding their applications in various fields. The study details zeolites' significance across industrial and scientific domains, outlining synthesis methods and size control techniques. The review emphasizes successful encapsulation and functionalization strategies for drug delivery, highlighting their role in enhancing drug stability and enabling targeted delivery. Advanced characterization techniques contribute to a comprehensive understanding of zeolite-based drug delivery systems. Addressing potential carcinogenicity, the review discusses environmental impact and risk assessment, stressing the importance of safety considerations in nanoparticle research. In biomedical applications, zeolites play vital roles in antidiarrheal, antitumor, antibacterial, and MRI contrast agents. Clinical trials featuring zeolite-based interventions underscore zeolite's potential in addressing diverse medical challenges. In conclusion, zeolite-based nanoparticles emerge as promising tools for targeted drug delivery, showcasing diverse applications and therapeutic potentials. Despite challenges, their unique advantages position zeolites at the forefront of innovative drug delivery systems.

Stability of intravenous medicines - evidence of maximum temperature reached in both summer and winter within soft shell elastomeric pumps.

OBJECTIVE: Elastomeric devices or pumps are a valuable tool to deliver outpatient parenteral therapy and have been used for administration of chemotherapy, antibiotics and pain medication. A key determinant of effective treatment is to consider the stability of medicines within these devices. It is widely known that an increase in temperature positively correlates to an increase in drug degradation. The objective of our work was to measure the temperature within soft shell elastomeric devices, under simulated outpatient treatment conditions in summer and winter months, and to determine the maximum temperature reached within these periods of use. METHODS: Thermocouples were inserted within soft shell Easypump II (B Braun Medical, Sheffield, UK) elastomeric pumps and the temperature was monitored under simulated outpatient conditions during cold and warm weather with different fill volumes. Temperature monitoring was also conducted with varying levels of insulation around the devices. RESULTS: Our results show that internal temperatures remained below 32°C±1°C in winter and summer months, including during times defined as a heatwave. Fill volume and ambient temperature were shown to be significant factors affecting the internal temperatures reached. CONCLUSION: A soft shell Easypump II elastomeric pump, if used within its carry pouch, will maintain the internal solution below a temperature of 32°C±1°C if patients correctly adhere to handling guidance. Our results show that further improvements to the insulation material used in carry pouches can significantly restrict the rate of temperature rise within the pumps and will give more assurance in relation to preventing degradation especially considering the increases in extreme weather conditions observed in recent years due to global warming.

Long-Term Stability of Glycopyrrolate Oral Solution Galenic Compound at Different Storage Conditions.

Glycopyrrolate is a competitive muscarinic receptor antagonist used in the treatment of sialorrhea, especially in pediatrics. Degradation research was conducted to better understand the stability of the active pharmaceutical ingredient (API). Using an HPLC-UV method, we evaluated the chemical stability of the oral solution of the galenic compound glycopyrrolate 0.5 mg/mL under different storage conditions. Method validation was performed according to the International Council for Harmonization (ICH) Q2(R2) guidelines. The results of the stability study of the galenic compound in different storage conditions, with the exception of those stored in glass containers at 45 °C for more than 3 months, were stable (100 ± 10% of the nominal concentration). The aim of this work was to study the stability of the galenic compound glycopyrrolate in two different types of containers and at three different storage temperatures. Glycopyrrolate showed degradation beyond the limits only in glass at 45 °C and after 2 months of storage. The results indicate that oral liquid dosage forms of glycopyrrolate are stable for at least 210 days when stored at room temperature or at 4 °C, in glass or PET, for at least 7 months, maintaining product quality according to the standards established by the European Pharmacopoeia, ensuring long-term coverage for pediatric patient therapies.

Long-term stability of esketamine in polypropylene syringes at 5 ± 3°C.

OBJECTIVE: Esketamine (Vesierra) is a molecule, used alone or in combination, to induce and maintain general anaesthesia and to relieve pain in emergency medicine. The aim of this study is to evaluate the long-term physicochemical stability of a 1 mg/mL solution of esketamine diluted in 0.9% sodium chloride (NaCl) and stored in polypropylene syringes at 5±3°C during 65 days (64+1 day at 22±3°C) and 72 hours at 22±3°C (room temperature), in order to centralise preparation under aseptic conditions in hospital pharmacy. METHODS: Ten syringes were prepared under aseptic conditions. Five syringes were stored at 22±3°C for 3 days, and the five others were stored at 5±3°C for 64 days (+ 1 day at room temperature). The stability was periodically investigated. Particle appearance or colour changes were checked by visual inspection. A research of crystals was performed under the microscope. pH was followed to assess its stability. The turbidity of the solutions was estimated by a measure of optical densities at 350, 410 and 550 nm. The molecule concentrations were measured by ultra-high performance liquid chromatography (UHPLC) coupled with a photodiode array detection (PDA), using a newly developed method. RESULTS: Based on microscopic examination, no crystals were observed, during the observation period. pH and absorbances at 350, 410 and 550 nm were also stable. Macroscopically, there was no change in colour and appearance of opacity, turbidity or precipitation. Statistical analysis indicates that 1 mg/mL esketamine solutions were chemically stable under these conditions, given that less than 5% of the solutions have lost more than 10% of their initial content during the study based on the prediction interval. CONCLUSIONS: One mg/mL solutions of esketamine hydrochloride are physically and chemically stable after production, for at least 72 hours at 22±3°C and 64 days at 5±3°C (+ 1 day at room temperature).

Drug-Modified Contact Lenses-Properties, Release Kinetics, and Stability of Active Substances with Particular Emphasis on Cyclosporine A: A Review.

The following review focuses on the manufacturing and parameterizing of ocular drug delivery systems (DDS) using polymeric materials to create soft contact lenses. It discusses the types of drugs embedded into contact lenses, the various polymeric materials used in their production, methods for assessing the mechanical properties of polymers, and techniques for studying drug release kinetics. The article also explores strategies for investigating the stability of active substances released from contact lenses. It specifically emphasizes the production of soft contact lenses modified with Cyclosporine A (CyA) for the topical treatment of specific ocular conditions. The review pays attention to methods for monitoring the stability of Cyclosporine A within the discussed DDS, as well as investigating the influence of polymer matrix type on the stability and release of CyA.

Chemical Stability of Lorazepam Oral Solution Repackaged in Plastic Oral Syringes at Room and Refrigerated Temperature.

Purpose: Generic lorazepam oral solution is supplied in a 30 mL multi-dose bottle requiring protection from light and refrigeration, with a beyond use date of 90 days once the bottle is opened. The repackaging of 1 mL doses of lorazepam oral solution into oral syringes allows for facilitated dispensing, yet no available data supports repackaging and storing lorazepam oral solution in syringes. The validation and application of a stability-indicating high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method for the quantification of lorazepam allowed for the determination of the stability of lorazepam oral solution when stored in oral syringes. Methods: A stability-indicating HPLC-UV method was developed for the quantification of lorazepam in oral solution. The method was validated using guidance from USP < 1225 >. For the stability investigation, 2 mg/mL lorazepam oral solution was aliquoted into clear plastic oral syringes in 1 mLmilliliter doses from 2 multi-dose stock bottles and randomly allocated for storage in room temperature or refrigerated environment. Baseline lorazepam concentrations were measured on the day the study was initiated and designated as 100% initial concentration samples. Subsequent samples were analyzed in triplicate at time points of 24, 48, and 96 hours and 7, 10, 14, 21, 30, and 60 days. Results: The calibration curves on three non-consecutive days met the linearity criteria of R 2 > 0.99. Inter- day and intra-day precision and accuracy (percent relative standard deviation and percent error) were ≤2% over three days. During the stability investigation, percent initial concentration of lorazepam from room and refrigerated syringes remained above 90% for the duration of the study. Conclusion: The stability-indicating HPLC-UV method was successfully applied to the investigation of lorazepam oral solution stability when stored in syringes at room and refrigerated temperatures. The emergent need for use of lorazepam concentrate for inpatients and the restrictions of how the medication is supplied necessitated a need for the evaluation of repackaging into unit dose syringes for immediate availability from automated dispensing cabinets. Lorazepam oral solution stored in clear plastic syringes maintained greater than 90% initial concentration at both room and refrigerated temperatures for 60 days.

Stability of clozapine tablets repackaged in dose administration aids using repackaging machines.

BACKGROUND: The use of dose administration aids in automated ward dispensing devices requires the repackaging of medications, which may impact their stability compared with the original manufacturer's packaging. OBJECTIVES: This study aimed to assess the physical and chemical stability of clozapine tablets for up to 84 days after repackaging. METHODS: A total of 900 tablets of clozapine 100 mg (Viatris) were repackaged and stored under five different conditions to conduct physical and chemical stability tests on days 0, 28, 56 and 84. The results were compared with control tablets in their original packaging. Visual inspections of tablet appearance were performed. Physical tests included assessments of mass uniformity, friability and resistance to crushing, following the standards of the European Pharmacopoeia 11th edition. The chemical stability was determined using ultra-high performance liquid chromatography with tandem-mass spectrometry detection (UHPLC-MS/MS) to measure clozapine concentration, N-desmethyl-clozapine, and monitor clozapine degradation to detect formation of any degradation products other than N-desmethyl-clozapine. RESULTS: Visual examination showed changes in the appearance of tablets only in those stored under UV light. Mass uniformity met standards for all tablets over 84 days. None passed the friability test due to tablet cracking after tumbling. A gradual deterioration in tablet hardness was observed with the resistance to crushing test. In terms of chemical stability, N-desmethyl-clozapine was undetected in any of the tablets stored under all conditions, and the mean concentration of clozapine remained within the target range over 84 days. CONCLUSION: N-desmethyl-clozapine was not detected and clozapine concentrations remained stable under all storage conditions. The tablets were compliant with the mass uniformity test in each condition. However, the tablets were cracked in the friability test and gradual deterioration in tablet hardness was observed. In the light of these results, the Vinatier Hospital pharmacy has chosen to establish a shelf life for clozapine tablets of 84 days.

[Translated article] Physicochemical and microbiological stability study of two new preservative-free methylprednisolone eye drops.

OBJECTIVE: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 and 10 mg/mL eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome. METHOD: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5±3 °C), at room temperature (25±2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones. RESULTS: The eye drops stored at 5 °C were the most stable; in the 1 mg/mL eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/mL eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/mL, presented a white precipitate from day 14 and 28, respectively. Non-refrigerated 1 mg/mL eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers. CONCLUSIONS: 1 mg/mL MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/mL eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.

An Overview of Degradation Strategies for Amitriptyline.

Antidepressant drugs play a crucial role in the treatment of mental health disorders, but their efficacy and safety can be compromised by drug degradation. Recent reports point to several drugs found in concentrations ranging from the limit of detection (LOD) to hundreds of ng/L in wastewater plants around the globe; hence, antidepressants can be considered emerging pollutants with potential consequences for human health and wellbeing. Understanding and implementing effective degradation strategies are essential not only to ensure the stability and potency of these medications but also for their safe disposal in line with current environment remediation goals. This review provides an overview of degradation pathways for amitriptyline, a typical tricyclic antidepressant drug, by exploring chemical routes such as oxidation, hydrolysis, and photodegradation. Connex issues such as stability-enhancing approaches through formulation and packaging considerations, regulatory guidelines, and quality control measures are also briefly noted. Specific case studies of amitriptyline degradation pathways forecast the future perspectives and challenges in this field, helping researchers and pharmaceutical manufacturers to provide guidelines for the most effective degradation pathways employed for minimal environmental impact.

Essential considerations towards development of effective nasal antibiotic formulation: features, strategies, and future directions.

INTRODUCTION: Intranasal antibiotic products are gaining popularity as a promising method of administering antibiotics, which provide numerous benefits, e.g. enhancing drug bioavailability, reducing adverse effects, and potentially minimizing resistance threats. However, some issues related to the antibiotic substances and nasal route challenges must be addressed to prepare effective formulations. AREAS COVERED: This review focuses on the valuable points of nasal delivery as an alternative route for administering antibiotics, coupled with the challenges in the nasal cavity that might affect the formulations. Moreover, this review also highlights the application of nasal delivery to introduce antibiotics for local therapy, brain targeting, and systemic effects that have been conducted. In addition, this viewpoint provides strategies to maintain antibiotic stability and several crucial aspects to be considered for enabling effective nasal formulation. EXPERT OPINION: In-depth knowledge and understanding regarding various key considerations with respect to the antibiotic substances and nasal route delivery requirement in preparing effective nasal antibiotic formulation would greatly improve the development of nasally administered antibiotic products, enabling better therapeutic outcomes of antibiotic treatment and establishing appropriate use of antibiotics, which in turn might reduce the chance of antibiotic resistance and enhance patient comfort.

Physicochemical and microbiological stability study of two new preservative-free methylprednisolone eye drops. / Estudio de estabilidad fisicoquímica y microbiológica de dos nuevos colirios de metilprednisolona sin conservantes.

OBJECTIVE: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 mg/ml and 10 mg/ml eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome. METHOD: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5 ±3 °C), at room temperature (25 ± 2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones. RESULTS: The eye drops stored at 5 °C were the most stable; in the 1 mg/ml eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/ml eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/ml, presented a white precipitate from day 14 and 28 respectively. Non-refrigerated 1 mg/ml eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers. CONCLUSIONS: 1 mg/ml MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/ml eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.

Effects of omitting titanium dioxide from the film coating of a pharmaceutical tablet - An industrial case study of attempting to comply with EU regulation 2022/63.

Recently, concerns have been raised about the safety of titanium dioxide (TiO2), a commonly used component of pharmaceutical film coatings. The European Union has recently prohibited the application of this material in the food industry, and it is anticipated that the same will happen in the pharmaceutical industry. For this reason, pharmaceutical manufacturers have to consider the possible impact of removing TiO2 from the film coating of tablets. In this paper, we present a case study of a commercially produced tablet where the film coating containing TiO2 was replaced with a coating using calcium carbonate (CaCO3) or with a transparent coating. The performance of the coatings was compared by measuring the moisture absorption rate and the dissolution profile of the tablets. In these regards, there were negligible differences between the coating types. The tablets contained a highly photosensitive drug, the ability of the coatings to protect the drug was evaluated through environmental stability and photostability measurements. The HPLC results showed that the inclusion of TiO2 does not provide additional benefits, when humidity and thermal stress is applied, however its role was vital in protecting the drug from external light. There were several decomposition products which appeared in large quantities when TiO2 was missing from the coating. These results imply that photosensitivity is an issue, replacing TiO2 will be challenging, though its absence can be tolerated when the drug does not need to be protected from light.

Biopolymeric Nanogel as a Drug Delivery System for Doxorubicin-Improved Drug Stability and Enhanced Antineoplastic Activity in Skin Cancer Cells.

In this study, doxorubicin was loaded in a chitosan-albumin nanogel with the aim of improving its stability and exploring the potential of the system in the treatment of skin cancer. Infrared spectroscopy and X-ray diffraction confirmed the encapsulation of the drug. Transmission electron microscopy revealed the spherical shape of the nanogel particles. The drug-loaded nanogel was characterized with a small diameter of 29 nm, narrow polydispersity (0.223) and positive zeta potential (+34 mV). The exposure of encapsulated doxorubicin to light (including UV irradiation and daylight) did not provoke any degradation, whereas the nonencapsulated drug was significantly degraded. In vitro studies on keratinocytes (HaCaT) and epidermoid squamous skin carcinoma cells (A-431) disclosed that the encapsulated doxorubicin was more cytotoxic on both cell lines than the pure drug was. More importantly, the cytotoxic concentration of encapsulated doxorubicin in carcinoma cells was approximately two times lower than that in keratinocytes, indicating that it would not affect them. Thus, the loading of doxorubicin into the developed chitosan-albumin nanogel definitely stabilized the drug against photodegradation and increased its antineoplastic effect on the skin cancer cell line.

Evaluating drug stability and sterility in single-dose vials when accessed with a closed system transfer device.

Background: Impact of drug wastage is a legitimate and persistent concern. Financial impact of drug waste is borne by the hospital network, patients, and healthcare systems. Measures to reduce drug wastage may have a positive impact throughout healthcare systems. Objective: This study investigated the stability and sterility of single-dose vials when repeatedly accessed with a closed system transfer device. By evaluating the sterility and stability, these results may be used to validate the extension of vial usage and lead to potential drug wastage reduction. Methods: Sterility testing was performed in accordance with US Pharmacopeia 71. A closed system transfer device was incorporated into simulated compounding tasks, utilizing growth media. Simulated compounding tasks were performed in the clinical environment, followed by incubation to stimulate growth. Stability testing was performed in accordance with US Pharmacopeia monographs at multiple timepoints post access. Test samples were comparatively tested via high-performance liquid chromatography to freshly opened vials at each timepoint. Results: No growth was observed in test samples. Control vials displayed growth, where appropriate. The drugs retained stability, when compared to freshly opened vials at 0, 24, 48, and 72 h, post access. Conclusions: This study confirms that closed system transfer devices do not contribute to microbial contamination of drug vials, following the repeated access, for up to 7 days and the tested drugs retained equivalent chemical stability for up to 72 h post access. This study may offer a manner by which a facility may assess single-dose vials' sterility and stability, following repeated access by a closed system transfer device.

Physicochemical Stability and Compatibility of Mixtures of Ropivacaine with Dexamethasone or Betamethasone for Epidural Steroid Injections: An In Vitro Study.

BACKGROUND: Epidural steroid injections are widely used to treat spinal and radiating pain. However, crystal formation has recently been reported in mixtures of ropivacaine and nonparticulate steroids, commonly used in epidural steroid injections. OBJECTIVES: Our study assessed the physicochemical stability of mixtures of different nonparticulate steroids and ropivacaine and aimed to propose a safe regimen for epidural steroid injections. STUDY DESIGN: An in vitro protocol was used to examine the physicochemical stability of epidural steroid injection mixtures most commonly used at our institution. SETTING: In vitro laboratory study. METHODS: Twelve solutions were prepared by mixing 0.75% or 0.2% ropivacaine with dexamethasone or betamethasone at volume ratios of 1:1, 2:1, and 3:1 in propylene syringes at 24°C. The physical properties of the mixtures were observed with the naked eye and under a microscope, and their pH was measured. The concentration of each drug in the mixture was evaluated using high-performance liquid chromatography. RESULTS: None of the ropivacaine and dexamethasone mixtures showed macroscopic or microscopic crystal formation after 2 hours, and there were no significant changes in pH. The concentrations of the 2 drugs remained stable for up to 2 hours. In contrast, at least 10 mu-m crystals were observed microscopically and macroscopically in all mixtures of ropivacaine and betamethasone; the ropivacaine concentration was reduced by > 10% after one hour. LIMITATIONS: Confirming the stability of drugs in vitro does not ensure that their pharmacokinetics and pharmacodynamics remain unaltered in vivo. CONCLUSION: The combination of ropivacaine and betamethasone should be avoided because of their physicochemical instability. Combinations of ropivacaine and dexamethasone should be administered cautiously because they are more physicochemically stable than combinations of ropivacaine and betamethasone.