Assessment of Functional and Physical Performances of Pre-filled Syringes in Deep Cold Storage Conditions.

The recent emergence of new drug technologies such as messenger ribonucleic acid-based vaccines developed to fight the outbreak of the COVID-19 global pandemic has driven increased demand for delivery solutions capable of withstanding deep cold storage conditions down to -50°C, and even down to -80°C. Although significant data exist for deep cold storage in vials, little evidence is available for pre-filled syringes. Because pre-filled syringes serve as both the storage container and the delivery mechanism, there are additional risks to performance that must be evaluated, such as plunger gliding performance, syringe lubrication, silicone layer stability, and container closure integrity (CCI). In the present study, a comprehensive assessment of functional and physical performances of pre-filled syringes (PFS filled with water) was performed after one or multiple freeze/thaw (F/T) cycles between ambient temperature and various temperature cycles including -40°C, -50°C or -80°C for both 'staked needle' and 'luer lock' configurations. The experiments were guided by historical normative methods such as ISO 11040-4 and USP <1207> and combined with headspace gas analysis for barrel-stopper tightness testing. In addition, they were complemented with a novel approach, namely in situ real-time optical imagery, to track plunger stopper movement during the F/T cycle. The findings indicated that there is no significant impact on the functional performances from F/T down to -80°C, whereas no CCI risk was found after F/T down to -50°C.

Preservation of Mimosa tenuiflora Antiaflatoxigenic Activity Using Microencapsulation by Spray-Drying.

Mimosa tenuiflora aqueous extract (MAE) is rich in phenolic compounds. Among them, condensed tannins have been demonstrated to exhibit a strong antioxidant and antiaflatoxin B1 activities in Aspergillus flavus. Since antioxidant capacity can change with time due to environmental interactions, this study aimed to evaluate the ability of encapsulation by spray-drying of Mimosa tenuiflora aqueous extract to preserve their biological activities through storage. A dry formulation may also facilitate transportation and uses. For that, three different wall materials were used and compared for their efficiency. Total phenolic content, antioxidant activity, antifungal and antiaflatoxin activities were measured after the production of the microparticles and after one year of storage at room temperature. These results confirmed that encapsulation by spray-drying using polysaccharide wall materials is able to preserve antiaflatoxin activity of Mimosa tenuiflora extract better than freezing.

Preventing Home Medication Administration Errors.

Medication administration errors that take place in the home are common, especially when liquid preparations are used and complex medication schedules with multiple medications are involved; children with chronic conditions are disproportionately affected. Parents and other caregivers with low health literacy and/or limited English proficiency are at higher risk for making errors in administering medications to children in their care. Recommended strategies to reduce home medication errors relate to provider prescribing practices; health literacy-informed verbal counseling strategies (eg, teachback and showback) and written patient education materials (eg, pictographic information) for patients and/or caregivers across settings (inpatient, outpatient, emergency care, pharmacy); dosing-tool provision for liquid medication measurement; review of medication lists with patients and/or caregivers (medication reconciliation) that includes prescription and over-the-counter medications, as well as vitamins and supplements; leveraging the medical home; engaging adolescents and their adult caregivers; training of providers; safe disposal of medications; regulations related to medication dosing tools, labeling, packaging, and informational materials; use of electronic health records and other technologies; and research to identify novel ways to support safe home medication administration.

Physicochemical properties, microstructure, and storage stability of Pulicaria jaubertii extract microencapsulated with different protein biopolymers and gum arabic as wall materials.

This study aimed to evaluate the possibility of using gum arabic (GA) with different protein materials namely whey protein isolate (WP), sodium caseinate (SC), and soybean protein (SP) as wall materials to encapsulate Pulicaria jaubertii extract (PJ) using freeze-drying. Four formulations of microencapsulation of Pulicaria jaubertii extract (MPJE) were produced, including WPGA-MPJE, SCGA-MPJE, SPGA-MPJE, and GA-MPJE. The formulations were stored at 4 °C and 25 °C for 28 days to assess the storage stability. The results indicated that mixtures of proteins with GA improved the physicochemical properties and bioactive content of the MPJE compared to GA-MPJE. The SCGA-MPJE formula showed optimal values of particle size (450.13 nm), polydispersity index (0.33), zeta potential (74.63 mV), encapsulation efficiency (91.07%), total phenolic content (25.51 g GAE g-1 capsules), and antioxidants compounds, as well as presented a lower release of bioactive composites with high oxidative stability during storage at 4 °C and 25 °C. The microstructure of MPJE formulations showed a flat surface without any visible cracking on surfaces. The microcapsules prepared from protein mixtures with GA, especially the SCGA-MPJE formula, are the most efficient in encapsulating the plant extract derived from the PJ, which could be useful for application in various industrial fields.

Encapsulation of ginger oleoresin in co-crystallized sucrose: development, characterization and storage stability.

Ginger oleoresin was emulsified with gum acacia and encapsulated in a sucrose matrix by co-crystallization. The increased void space and surface area of sucrose provided a porous base for the incorporation of oleoresin. This co-crystallization led to modification from crystalline to irregular agglomerates, as evident from X-ray diffraction and differential scanning calorimetry. Hygroscopicity, water sorption isotherms and water activity demonstrated changes due to the change in crystallinity of sucrose. The active components such as [6]-, [8]- and [10]-gingerols and [6]-shogaol were quantified by HPLC. The encapsulation efficiency of [6]-gingerol was 45.59%. The storage kinetics at different relative humidity levels and temperatures indicated [6]-gingerol to be the most stable among the gingerols studied. A temperature of 25 °C and relative humidity of 33% proved to be the best storage conditions for the ginger flavoured sugar cubes. Thus, co-crystallization for the encapsulation of ginger oleoresin serves a dual purpose, i.e., protection and a mode of delivering a spicy flavour.

Spray dried nanoemulsions loaded with curcumin, resveratrol, and borage seed oil: The role of two different modified starches as encapsulating materials.

Recently, food industries are directing on the promotion of innovative food matrices fortified with bioactive compounds in order to enhance the consumer's health. Octenyl succinic anhydride modified starches (OSA-MS) such as Hi-cap100 (HCP) and purity gum 2000 (PUG) were used to fabricate emulsions co-entrapped with borage seed oil (BSO), resveratrol (RES) and curcumin (CUR), which were further spray dried to obtain powders. The fabricated microcapsules loaded with BSO, RES, and CUR displayed excellent dissolution performance, high encapsulation efficiency (≈93.05%) as well as semi-spherical shape, revealed via scanning electron microscopy (SEM). We also evaluated the impact of storage time (4 weeks) and temperature (40 °C) on the physicochemical characterization of OSA-MS coated microcapsules. Microcapsules coated with HCP exhibited greater oxidative stability, lower water activity and moisture contents rather than PUG coated microcapsules during storage because of its good film-forming properties. Addition of CUR enhanced the oxidative stability and retention of bioactive compounds. HCP microcapsules loaded with BSO + RES + CUR presented supreme retention of RES (70.32%), CUR 81.6% and γ-linolenic acid (≈ 96%). Our findings showed that CUR acted as an antioxidant agent; also, lower molecular weight OSA-MS as wall material could be used for the entrapment of bioactive compounds and promotion of innovative food products.

Essential Oils from Piper lhotzkyanum Kunth Leaves from Brazilian Atlantic Forest: Chemical Composition and Stability in Different Storage Conditions.

This work aimed to evaluate the impact of different storage conditions and light and temperature exposures on the visual aspect and chemical composition of the essential oil (EO) of Piper lhotzkyanum Kunth, obtained from leaves by hydrodistillation from a region of high altitude. For this purpose, aliquots of the EO were stored for up to 90 days (a) under a refrigerator condition of 5 ± 3°C, (b) under a long-term (LT) condition of 30 ± 2°C and 75 ± 5% relative humidity (RH) and an accelerated condition (AS) of 40 ± 2°C and 75 ± 5% RH, and (c) in a photostability test achieved in amber and colorless glass vials. The changes were monitored on days 0 (control), 60, and 90 for the refrigerator, LT, and AS conditions. All EO chemical analyses were assessed by GC-FID and GC-MS for quantification and identification, respectively. It is reported, for the first time, that the EO of P. lhotzkyanum is rich in the sesquiterpenes ß-elemene and α-zingiberene. No significant changes in the EO was observed, revealing a minimal impact of temperature on the sample at the different storage conditions. However, there was a change in the content of α-zingiberene to bicyclogermacrene after exposure to light. The visual appearance of the samples was altered for all test conditions except the refrigerator condition. These results can potentially contribute to the product development of a bioactive EO from leaves of P. lhotzkyanum, a sesquiterpene rich natural material.

Deployment of response surface methodology to optimize microencapsulation of peroxidases from turnip roots (Brassica rapa L.) by double emulsion in PLA polymer.

In order to improve the preservation conditions and stability of peroxidase catalytic properties, a number of immobilization techniques have been widely developed. In this context, we set as objective, the optimization of synthesis and stability of microcapsules of peroxidases (POD) from turnip using polylactic acid (PLA) polymer with the double emulsion technique. The surfactant, polymer, and peroxidase concentrations were the optimized parameters. According to the results obtained using the Box-Behnken design, the optimal parameters found were 1.55% of PVA, 55 mg/mL of peroxidases, and 30 mg/mL of PLA polymer with an encapsulation efficiency of 57.29%. The scanning electron microscopy morphological characterization of the optimized microcapsules showed a regular spherical structure. Fourier transform infrared spectroscopy identified the specific functional groups and chemical bonds before and after microencapsulation. The elaborated microcapsules were characterized by an average size of 200 µm (mainly from 150 to 500 µm) with a low residual moisture content (2.26%) and the encapsulated peroxidases showed better thermal stability. The in vitro release of peroxidases confirmed that the microcapsules have an excellent sustained release in simulated gastric digestion. Encapsulated peroxidases' storage under 25 and 4 °C displays a good residual POD activity with about 60% of initial activities during 80 days of storage, whereas free POD losses its initial activity within 15 and 30 days, respectively. The obtained results are promising for the development of effective therapeutic treatment of some intestinal troubles due to oxidative stress. PRACTICAL APPLICATION: Brassica rapa L. root is well known for its richness on peroxidases and thus presents an interesting potential for developing high added value products. In order to preserve the activity of extracted peroxidases (POD) from turnip roots, microencapsulation was optimized using a polylactic acid polymer. The encapsulated POD showed the maintenance of its activity under the effect of different storage conditions (time and temperature) and demonstrated resistance to gastric acidity. According to the obtained results, the encapsulation of peroxidases opens up medicine and pharmaceutical applications such as intestinal and colic protection against inflammations.

Topical delivery of l-ascorbic acid spanlastics for stability enhancement and treatment of UVB induced damaged skin.

l-Ascorbic acid (LAA) is considered a powerful antioxidant that protects skin from premature aging. Maintaining the stability of vitamin C remains the biggest challenge in cosmeceuticals. Our main aim is the entrapment of high dose of vitamin C in spanlastic vesicles to provide maximum stability and efficacy. LAA-loaded spanlastics were prepared by ethanol injection method and were characterized for entrapment efficiency (EE%), particles size (PS), polydispersity index (PDI), zeta potential, deformability index (DI) and in vivo skin permeation. Selected spanlastics formula composed of span 60 and tween 60 (5:1) showed highest EE% of 89.77 ± 3.61% (w/w), high deformability of 11.13 ± 1.145 as well as good physical and chemical stability for 6 months. Improved drug penetration into stratum corneum (SC) was obtained from spanlastics compared to topical LAA solution. Quantitative real time PCR revealed that MMP2 and MMP9 levels were significantly suppressed in response to LAA spanlastics treated rats by 30.4% and 65.3%, respectively, when compared to the control group after exposure to UV irradiation. Results were confirmed by western blot analysis. Histopathological study of rat skin after UV irradiation revealed that application of LAA-loaded spanlastics provided the highest skin protection compared to UVB and LAA solution treated group which was evident by the normal thick epidermal morphology and the densely arranged dermal collagen fibers. LAA-loaded spanlastics successfully improved LAA stability, skin permeation and antioxidant protection against skin photodamage.

Effect of maltodextrin combination with gum arabic and whey protein isolate on the microencapsulation of gurum seed oil using a spray-drying method.

This study aimed to evaluate the potential of maltodextrin (MD) combination with gum arabic (GA), and whey protein isolate (WPI) on the microencapsulation of gurum seeds oil by a spray-drying method. Three formulations of protein-based (PB) (WPI: MD, 2:1), carbohydrate-based (CHOB) (GA: MD, 2:1), and mixed (MIX) (WPI: GA: MD, 1:1:1) wall materials were designed. The moisture content and water activity were in the range of 1.65-3.67% and 0.17-0.31, respectively, which is suitable for long-term storage. The best results were achieved when gurum seed oil was microencapsulated with carbohydrate-based, where it had the highest microencapsulation yield (92.80%) and microencapsulation efficiency (97.38%). Carbohydrate-based showed the highest relative crystallinity (32.25%) and the temperature of the glass transition (58.20 °C). FT-IR revealed that the oil was well encapsulated in the microcapsules. SEM of microcapsules showed spherical shapes without any apparent cracking on the surfaces. During the oxidative stability study, carbohydrate-based microencapsulation was the wall material that best protected the active materials against lipid oxidation.

The Role of Platelet Homeostasis in a Novel Topical PRP Formulation.

BACKGROUND: Topical platelet-rich plasma (PRP) must demonstrate stability to insure biologic activity in aesthetic medicine. OBJECTIVE: The objective of this research was to evaluate the role of platelet homeostasis in a novel PRP topical cosmetic formulation to provide facial appearance improvement. METHODS: The stability of the topical PRP formulation was evaluated in vitro followed by clinical in vivo testing. The in vitro evaluation examined platelet stability and morphology over a 90-day period within the preservative cosmetic base utilizing ELISA and light microscopy (LM)/scanning electron microscopy (SEM). The in vivo clinical study enrolled 20 subjects in a 120-day double blind split face study to evaluate the effect of 5–7x concentrated PRP compared to 2–3x concentrated PRP on facial photoaging. Cosmetic effect was evaluated by the subject and the dermatologist investigator on a 5-point ordinal scale at baseline, week 8, and week 16. RESULTS: 90-day stability for the topical PRP formulation was verified via ELISA and LM/SEM. ELISA showed the PRP was more inactive than control conditions via analyte concentration curves (PDGF-AB, EGF, and P-Selectin). LM/SEM demonstrated the PRP had less aggregation/activation over time within the cosmetic base and that refrigeration is superior to room-temperature storage thus delaying full platelet degranulation. The in vivo clinical study demonstrated parity between 20ml and 60ml PRP in terms of clinical efficacy. CONCLUSION: Platelets remain viable for up to 90 days in a refrigerated cosmetic vehicle with demonstrated topical clinical PRP facial benefits. PRP kits of 20ml and 60ml volumes for topical PRP are equally efficacious. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5495.

Holistic Extractables and Leachables Program: Evaluations of Prefilled Syringe Systems for Biotechnology Products.

Prefilled syringes (PFS) are a container and delivery device of choice for storing and administering therapeutic protein products to patients. Addressing concerns and regulatory expectations related to the risk to biologic drug product quality and patient safety from PFS requires implementation of an extractable and leachable program based on understanding of materials, risk assessment, review of existing literature, and testing supported by a sound scientific foundation. Extractables and leachables data generated as part of a thorough and holistic program are presented for five PFS systems, including glass and plastic syringes filled with 12 biologic drug products encompassing the implementation of traditional and single-use biotechnology manufacturing processes. The comprehensive extractables and leachables data presented demonstrate and substantiate a holistic extractable and leachable program designed to ensure product quality and patient safety.

The role of encapsulant materials on the stability of bioactive compounds of red ginger (Zingiber officinale Roscoe. var. Rubrum) extract powder during storage.

The aims of this study were to evaluate the role of encapsulant materials on the stability of bioactive compounds of red ginger extract powder during storage and determine the composition of the encapsulant materials which produced red ginger extract powder with best stability of bioactive compounds during storage. This study consisted of three compositions of encapsulant materials which are maltodextrin:gum arabic with ratio 10:0, 8:2, and 5:5. The results showed that several compositions of encapsulant materials produced different stability of bioactive compounds of red ginger extract powder. Based on the study result, increasing amount of gum arabic used had better protection to the stability of bioactive compounds of the powders during storage.

Chemical Evaluation of the Effects of Storage Conditions on the Botanical Goldenseal using Marker-based and Metabolomics Approaches.

Hydrastis canadensis, commonly known as goldenseal, is a botanical native to the southeastern United States that has been used for the treatment of infection. The activity of goldenseal is often attributed to the presence of alkaloids (cyclic, nitrogen-containing compounds) present within its roots. Chemical components of botanical supplements like goldenseal may face degradation if not stored properly. The purpose of the research was to analyze the stability of known and unknown metabolites of H. canadensis during exposure to different storage conditions using mass spectrometry. Three abundant metabolites of H. canadensis, berberine, canadine, and hydrastine, were chosen for targeted analysis, and the stability of unknown metabolites was evaluated using untargeted metabolomics. The analysis and evaluation of H. canadensis samples were performed utilizing LC-MS and Principal Component Analysis (PCA). The research project focused on identifying the chemical changes in the metabolite content of H. canadensis under different temperature conditions (40°C ± 5°C, 20°C ± 5°C , and 4°C ± 5°C), different light:dark (hr:hr) cycles (16:8, 12:12, and 0:24), and different sample conditions (powdered roots versus whole roots) over a six month period. The results of this 6-month study revealed that the storage conditions evaluated had no significant effects on the chemical composition of H. canadensis roots. Hence, as long as H. canadensis roots are stored within the storage conditions tested in the study, no significant changes in chemical compositions of metabolites are expected.

Cereal bran protects vitamin A from degradation during simmering and storage.

Food supplementation with vitamin A is an efficient strategy to combat vitamin A deficiency. The stability of vitamin A during cooking and storage is, however, low. We here show that cereal bran protects retinyl palmitate (RP) during simmering and storage. Native wheat bran stabilized RP the most during simmering. About 75% RP was recovered after 120 min of cooking, while all RP was lost after 80 min in the absence of bran. Heat-treated rice bran protected RP the best during forced storage, with a 35% recovery after 8 weeks. RP was degraded entirely in the absence of bran in less than one week. Results suggested that the physical entrapment of oil within the large wheat bran particles protects RP from the action of water and pro-oxidants during simmering. During storage, the high amount and diversity of lipid components present in rice bran are presumably responsible for its protective effect.

Stability of N-Acetylcysteine (NAC) in Standardized Pediatric Parenteral Nutrition and Evaluation of N,N-Diacetylcystine (DAC) Formation.

The ESPGHAN/ESPEN/ESPR-Guidelines on pediatric parenteral nutrition (PPN) recommend the administration of the semiessential amino acid (AA) cysteine to preterm neonates due to their biochemical immaturity resulting in an inability to sufficiently synthetize endogenous cysteine. The soluble precursor N-acetylcysteine (NAC) is easily converted into bioavailable cysteine. Its dimer N,N-diacetylcystine (DAC) is almost unconvertable to cysteine when given intravenously resulting in a diminished bioavailability of cysteine. This study aims to understand the triggers and oxidation process of NAC to DAC to evaluate possibilities of reducing DAC formation in standardized PPN. Therefore, different air volumes (21% O2) were injected into the AA compartment of a standardized dual-chamber PPN. O2 concentrations were measured in the AA solution and the headspaces of the primary and secondary packaging. NAC and DAC concentrations were analyzed simultaneously. The analysis showed that O2 is principally delivered from the primary headspace. NAC oxidation exclusively delivers DAC, depending on the O2 amount in the solution and the headspaces. The reaction of NAC to DAC being containable by limiting the O2 concentration, the primary headspace must be minimized during manufacturing, and oxygen absorbers must be added into the secondary packaging for a long-term storage of semipermeable containers.

Association rule mining for the ordered placement of traditional Chinese medicine containers: An experimental study.

In traditional Chinese medicine (TCM) clinics, the pharmacists responsible for dispensing the herbal medicine usually find the desired ingredients based on positions of the shelves (racks; frames; stands). Generally, these containers are arranged in an alphabetical order depending on the herbal medicine they contain. However, certain related ingredients tend to be used together in many prescriptions, even though the containers may be stored far away from each other. This can cause problems, especially when there are many patients and/or the limited number of pharmacists. If the dispensing time takes longer, it is likely to impact the satisfaction of the patients' experience. Moreover, the stamina of the pharmacists will be consumed quickly.In this study, we investigate on an association rule mining technology to improve efficiency in TCM dispensing based on the frequent pattern growth algorithm and try to identify which 2 or 3 herbal medicines will match together frequently in prescriptions. Furthermore, 3 experimental studies are conducted based on a dataset collected from a traditional Chinese medicine hospital. The dataset includes information for an entire year (2014), including 4 seasons and doctors. Afterward, a questionnaire on the usefulness of the extracted rules was administered to the pharmacists in the case hospital. The responses showed the mining results to be very valuable as a reference for the placement and ordering of the frames in the TCM pharmacies and drug stores.

[Changes of pigment components in Dendrobium catenatum flower under different storage conditions].

The flower color of Dendrobium catenatum(D. officinale) tends to fade during storage. In order to clarify the influence of storage conditions on the pigment components in flowers, two conditions were applied:temperature and illumination. The contents of pigments in the D. catenatum flower were determined by UV-Vis spectrophotometry and HPLC, and the changes of them during storage were analyzed. The results showed that illumination and temperature had an effect on the pigments of D. catenatum flower during sto-rage. Illumination significantly promoted the degradation of pigments. The contents of total chlorophyll, carotenoids and anthocyanins in the light samples were significantly lower than those in the dark. The total chlorophyll, carotenoids and anthocyanins in the light samples were decreased by 46.5%, 63.4%, and 69.2% respectively. Illumination had a greater effect on fat-soluble pigments than water-soluble pigments. Among the three temperature treatments, the contents of chlorophyll, carotenoid and anthocyanin were as follows:-20 ℃>4 ℃>room temperature, it is indicated that-20 ℃ was the best temperature to maintain the stability of pigment composition. The contents of chlorophyll a, chlorophyll b, ß-carotene, lutein and zeaxanthin in the light samples decreased by 34.8%, 69.0%, 72.5%, 61.6%, 36.1%, respectively. After storage for 5 months, the contents of chlorophyll, carotenoid and anthocyanin constituent at-20 ℃ was significantly higher than those at 4 ℃ and room temperature. The results show that light avoiding and low-temperature can effectively slow down the degradation of pigment components. Therefore, it is suggested that D. catenatum flower should be stored in light avoiding and low-temperature conditions in actual production and processing, which can prolong the usable time.

Development, characterization and stability evaluation of ciprofloxacin-loaded parenteral nutrition nanoemulsions.

In this study, two licensed total parenteral nanoemulsion formulations (Clinoleic® and Intralipid®) were loaded with ciprofloxacin (CP). The physicochemical characteristics and stability profiles of the formulations were investigated using a range of drug concentrations. Furthermore, formulation stability was evaluated over a period of six months at room temperature (RT) or 4 °C. Loading CP into nanoemulsions resulted in no significant differences in their measured droplet size, polydispersity index (PI), zeta potential, and pH. Drug entrapment efficiency (EE) was relatively high for all formulations, regardless of nanoemulsion type, and the drug release was sustained over 24 h. Stability studies of all formulations were performed at 4 °C and RT for 180 and 60 days, respectively. At 4 °C for 180 days, both Clinoleic® and Intralipid® formulations at a range of drug concentrations (1-10 mg/ml) showed high stabilities measured periodically by the average droplet sizes, PI, pH, and zeta potential values. Similar results, but pH values, were shown when the formulations for both nanoemulsion stored at RT for 60 days. Overall, this study has shown that CP was successfully loaded into clinically licensed TPN lipid nanoemulsions. The resultant CP-loaded nanoemulsion formulations demonstrated desirable physicochemical properties and were stable upon storage at 4 °C for up to six months.

Sterility and concentration of liposomal bupivacaine single-use vial when used in a multiple-dose manner.

OBJECTIVE: To evaluate the sterility of bupivacaine liposome injectable suspension (Nocita®) used in a multiple-dose fashion for 5 days. STUDY DESIGN: Triplicate liposomal bupivacaine vials were stored under two conditions, (1) room temperature (24°C) and (2) refrigerated temperature (5°C). A 3-mL aliquot was withdrawn from each vial daily. Samples were inoculated in tryptic soy broth in triplicate and then incubated for 24 hours at 37°C and subcultured every 48 hours onto blood agar and Sabouraud dextrose agar, respectively. Separate 1.5-mL aliquots of liposomal bupivacaine were centrifuged at 3500 g to separate liposome-encapsulated bupivacaine from the solution. Concentration of unencapsulated bupivacaine was analyzed via high-pressure liquid chromatography. Data were analyzed by using mixed effects procedure with multiple comparisons. SAMPLE POPULATION: Ten 20-mL vials of bupivacaine liposome injectable suspension stored under two conditions, (1) room temperature (24°C) and (2) refrigerated temperature (5°C). RESULTS: Five days of repeated withdrawal from the single-use vials yielded no bacterial growth. One control vial, which was opened and punctured once on the last day of the experiment, yielded fungal growth of an Aspergillus spp, likely an environmental contaminant. The concentration of free bupivacaine did not significantly differ until the fifth day of sampling. CONCLUSION: When aseptic technique was used, liposomal bupivacaine remained sterile for 5 days. Concentrations of free bupivacaine were unchanged from baseline for 4 days in both refrigerated and room temperature conditions. CLINICAL SIGNIFICANCE: Single-use liposomal bupivacaine vials can be used extralabel in a multiple-dose fashion for up to 4 days when stored either refrigerated or room temperature when sterile technique is used.