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Nefrologia : Publicacion Oficial de La... 2007
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Yakugaku Zasshi : Journal of the... 2015Recently, there has been a transition from glass to plastic injection containers in Japan. In our previous study, we suggested that plastic containers had less impurity... (Review)
Review
Recently, there has been a transition from glass to plastic injection containers in Japan. In our previous study, we suggested that plastic containers had less impurity contamination than glass containers. However, the use of some plasticizers has been limited because of their endocrine disrupting effects. Therefore, contamination has been a concern due to chemicals in injection solution packed with plastic containers. Indeed, in our recent study, photoinitiators were detected in an injection solution coming from plastic containers. Photoinitiators mainly exist in ink. We therefore speculated that ink originating from a photoinitiator directly printing on plastic containers had migrated into the injection solutions. In a clinical setting, plastic containers are very tractable because they are lightweight and less breakable. On the other hand, from a safety view point, these containers may be hazardous because of permeation by steam, ambient air or photoinitiators. In the present symposium, we will discuss the risk of photoinitiators leaking into injection solution packed with plastic containers, and countermeasures to avoid this risk.
Topics: Cell Survival; Drug Contamination; Drug Packaging; Endocrine Disruptors; Humans; Pharmaceutical Solutions; Photochemical Processes; Plastics
PubMed: 25747222
DOI: 10.1248/yakushi.14-00228-6 -
Journal of Pharmacy & Pharmaceutical... Aug 2005Prefomulation approach utilizing the fractional-ordered randomized blocked design was employed for the formulation development and stability testing of morphine solution. (Comparative Study)
Comparative Study
PURPOSE
Prefomulation approach utilizing the fractional-ordered randomized blocked design was employed for the formulation development and stability testing of morphine solution.
METHODS
Factors expecting to affect the stability of morphine were evaluated, i.e., vehicle, antioxidant, chelating agent, and pH of the solution. Eight formulations of a possible 16 were prepared according to the block design. The stability of the preparations was tested after 35 days of storage. The data of preformulation study were used for formulation development.
RESULTS
The presence of glycerin and ethylenediamine-tetraacetic acid in the formulation, and the pH of the solution adjusted to 4, stabilized morphine. The concentration of morphine decreased drastically in the formulations containing sodium metabisulfite, and those pH adjusted to 6. After 35 days, only 65% of morphine was found in the formulation containing sodium metabisulfite and pH adjusted to 6. The results of preformulation study were used for preparing oral morphine preparations. Samples were kept in amber glass bottles and stored at 4 degrees C and 25 degrees C/75% RH for 13 months. No precipitation of the four formulations was detected. Only a decrease of odor and a small increase of pH value of the preparations (< 0.3 units) were observed. More than 97% of morphine remained in all samples. The samples were free from microbial contamination.
CONCLUSION
Stable morphine solution formulations can be achieved with the utilization of the preformulation approach. They were stable more than 13 months when stored at 4 degrees C and 25 degrees C/75% RH.
Topics: Administration, Oral; Chemistry, Pharmaceutical; Drug Stability; Hydrogen-Ion Concentration; Morphine; Pharmaceutical Solutions; Technology, Pharmaceutical
PubMed: 16124948
DOI: No ID Found -
Biomaterials Mar 2020The availability of a wearable artificial kidney (WAK) that provides dialysis outside the hospital would be an important advancement for dialysis patients. The concept... (Review)
Review
The availability of a wearable artificial kidney (WAK) that provides dialysis outside the hospital would be an important advancement for dialysis patients. The concept of a WAK is based on regeneration of a small volume of dialysate in a closed-loop. Removal of urea, the primary waste product of nitrogen metabolism, is the major challenge for the realization of a WAK since it is a molecule with low reactivity that is difficult to adsorb while it is the waste solute with the highest daily molar production. Currently, no efficient urea removal technology is available that allows for miniaturization of the WAK to a size and weight that is acceptable for patients to carry. Several urea removal strategies have been explored, including enzymatic hydrolysis by urease, electro-oxidation and sorbent systems. However, thus far, these methods have toxic side effects, limited removal capacity or slow removal kinetics. This review discusses different urea removal strategies for application in a wearable dialysis device, from both a chemical and a medical perspective.
Topics: Dialysis Solutions; Humans; Kidneys, Artificial; Regeneration; Renal Dialysis; Urea; Wearable Electronic Devices
PubMed: 31958714
DOI: 10.1016/j.biomaterials.2019.119735 -
BMC Nephrology Nov 2021It has been noticed for years that ultrafiltration (UF) is important for survival in peritoneal dialysis. On the other hand, precise and convenient UF measurement...
BACKGROUND
It has been noticed for years that ultrafiltration (UF) is important for survival in peritoneal dialysis. On the other hand, precise and convenient UF measurement suitable for patient daily practice is not as straight forward as it is to measure UF in the lab. Both overfill and flush before fill used to be source of measurement error for clinical practice. However, controversy finding around UF in peritoneal dialysis still exists in some situation. The current study was to understand the difference between clinical measured UF and real UF. The effect of evaporation and specific gravity in clinical UF measurement were tested in the study.
METHODS
Four different brands of dialysate were purchased from the market. The freshest dialysate available in the market were intentionally picked. The bags were all 2 L, 2.5% dextrose and traditional lactate buffered PD solution. They were stored in four different conditions with controlled temperature and humidity. The bags were weighted at baseline, 6 months and 12 months of storage. Specific gravity was measured in mixed 24 h drainage dialysate from 261 CAPD patients when they come for their routine solute clearance test.
RESULTS
There was significant difference in dialysate bag weight at baseline between brands. The weight declined significantly after 12 month's storage. The weight loss was greater in higher temperature and lower humidity. The dialysate in non-PVC package lose less weight than PVC package. The specific gravity of dialysate drainage was significantly higher than pure water and it was related to dialysate protein concentration.
CONCLUSION
Storage condition and duration, as well as the type of dialysate package have significant impact in dialysate bag weight before use. Evaporation is likely to be the reason behind. The fact that specific gravity of dialysate drainage is higher than 1 g/ml overestimates UF in manual exchanges, which contributes to systemic measurement error of ultrafiltration in CAPD.
TRIAL REGISTRATION
ClinicalTrials.gov ID: NCT03864120 (March 8, 2019) (Understand the Difference Between Clinical Measured Ultrafiltration and Real Ultrafiltration).
Topics: Dialysis Solutions; Humans; Peritoneal Dialysis; Product Packaging; Specific Gravity; Ultrafiltration
PubMed: 34781890
DOI: 10.1186/s12882-021-02589-3 -
Drug Delivery Nov 2020Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive pulmonary disease that can cause fibrotic remodeling of the surrounding lung, thus leading to...
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive pulmonary disease that can cause fibrotic remodeling of the surrounding lung, thus leading to respiratory failure. Although IPF is the most common form of idiopathic interstitial pneumonia, the precise mechanisms underlying this condition remain unknown. In this study, we used total saponins of inhalation solution (TIS) to induce idiopathic bleomycin-induced pulmonary fibrosis in rats. The uniformity of delivery dose was investigated by analyzing the aerodynamic particle size distribution and drug stability. The potential of hydrogen potential of hydrogen (pH) of the inhalation solution was 7.0 and the solvent 0.9% NaCl solution, thus meeting physiological requirements for pulmonary drug administration. The delivery rate was 1.94 ± 0.16 mg·min and the total dose was 17.40 ± 0.04 mg. TIS was composed of five key components: notoginsenoside R, ginsenosides Rg, ginsenosides Re, ginsenosides Rb, and ginsenosides Rd. The mass median aerodynamic diameter (MMAD) for these five components were 3.62 ± 0.05 µm, 3.62 ± 0.06 µm, 3.65 ± 0.10 µm, 3.62 ± 0.06 µm, and 3.61 ± 0.05 µm, respectively. Fine particle fraction (FPF) was 66.24 ± 0.73%, 66.20 ± 0.89%, 66.07 ± 1.42%, 66.18 ± 0.79%, and 66.29 ± 0.70%, respectively. The MMAD for inhalation solutions needs to be 1-5 µm, which indicates that the components of TIS are suitable for inhalation. It is important to control the particle size of targeted drugs to ensure that the drug is delivered to the appropriate target tissue. experiments indicated that TIS exhibited high rates of deposition in lung tissue, thus indicating that pulmonary delivery systems may represent a good therapeutic option for patients.
Topics: Administration, Inhalation; Aerosols; Animals; Bleomycin; Drug Delivery Systems; Drug Stability; Hydrogen-Ion Concentration; Male; Models, Molecular; Panax notoginseng; Particle Size; Pharmaceutical Solutions; Protective Agents; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Saponins
PubMed: 33307846
DOI: 10.1080/10717544.2020.1856222 -
Seminars in Ophthalmology Jan 2022To describe the relationship between the number of Federal Drug Administration (FDA)-approved manufacturers and the price change of generic and branded topical eye drops.
PURPOSE
To describe the relationship between the number of Federal Drug Administration (FDA)-approved manufacturers and the price change of generic and branded topical eye drops.
METHODS
Retrospective analysis of topical eye drop medications with formulations listed in the FDA Orange Book and the National Average Drug Acquisition Cost database from 2013 to 2017.
RESULTS
The most frequently prescribed generic topical drugs were glaucoma medications (34%), antimicrobials (32%), anti-inflammatories (24%), mydriatics (5%), and anesthetics (5%). The most frequently prescribed branded topical drugs were anti-inflammatories (45%), glaucoma medications (32%), antimicrobials (21%) and dry eye medications (3%). From 2013 to 2017, generic eye drops had a median price decrease of 20% (IQR 32%) while branded eye drops had a median price increase of 44% (IQR 28%) ( < .001). A significant inverse association was identified between the price change of generic eye drops and the total number of all manufacturers (r = -.41, = .010), generic drug manufacturers (r = -.32, = .0496), and alternative branded drug manufacturers (r = -.57, = .002). There was no significant association between the price change of branded eye drops and number of manufacturers. Glaucoma (r = -.58, = .039) and anti-inflammatory (r = -.69, = .047) eye drops also had significant inverse associations with the number of generic manufacturers.
CONCLUSION
From 2013 to 2017, the price of generic eye drops decreased whereas the price of branded eye drops increased. Market competition was significantly inversely associated with price changes of generic eye drops but not branded eye drops.
Topics: Drug Costs; Drug Industry; Drugs, Generic; Humans; Ophthalmic Solutions; Retrospective Studies
PubMed: 33780301
DOI: 10.1080/08820538.2021.1906918 -
Medicina (Kaunas, Lithuania) Feb 2022: The cardioplegic arrest of the heart during cardiosurgical procedures is the crucial element of a cardioprotection strategy. Numerous clinical trials compare different...
: The cardioplegic arrest of the heart during cardiosurgical procedures is the crucial element of a cardioprotection strategy. Numerous clinical trials compare different cardioplegic solutions and cardioprotective protocols, but a relatively small number of papers apply to in vitro conditions using cultured cells. This work aimed to analyze whether it is possible to use the rat heart myocardium cells as an in vitro model to study the protective properties of St. Thomas cardioplegia (ST2C). The rat heart myocardium cells-H9C2 were incubated with cold cardioplegia for up to 24 h. After incubation, we determined: viability, confluency, and cell size, the thiol groups' level by modifying Ellman's method, Ki67, and Proliferating Cell Nuclear Antigen expression (PCNA). The impact on cells' morphology was visualized by the ultrastructural (TEM) study and holotomograpic 3D imaging. The viability and confluency analysis demonstrated that the safest exposure to ST2C, should not exceed 4h. An increased expression of Ki67 antigen and PCNA was observed. TEM and 3D imaging studies revealed vacuolization after the longest period of exposure (24). According to obtained results, we conclude that STC can play a protective role in cardiac surgery during heart arrest.
Topics: Animals; Cardioplegic Solutions; Heart; Heart Arrest, Induced; Myoblasts; Myocardium; Rats
PubMed: 35208603
DOI: 10.3390/medicina58020280 -
European Journal of Hospital Pharmacy :... Mar 2020Norepinephrine is a vasopressor frequently administered after dilution to treat hypotension and shocks in intensive care units. The stability of norepinephrine is known...
OBJECTIVES
Norepinephrine is a vasopressor frequently administered after dilution to treat hypotension and shocks in intensive care units. The stability of norepinephrine is known to be highly sensitive to storage conditions. Moreover, medication errors linked to the dilution step are frequent and may be deleterious for critically-ill patients, especially in intensive care units. This study aimed to evaluate the stability of ready-to-use diluted norepinephrine solutions prepared at two target concentrations (0.2 and 0.5 mg/mL), according to the summary of product characteristics, and stored for 365 days in two containers: AT-closed cyclic olefin copolymer vials, and polypropylene syringes.
METHODS
A fast reversed-phase liquid chromatography method coupled with an ultra-violet detector was developed to assess the chemical stability of norepinephrine solutions. Validation was conducted according to the linearity of the calibration ranges, selectivity, sensitivity, accuracy and precision. Dosage, sub-visible particle contamination, pH monitoring and sterility assays were performed. Chemical stability was maintained if the measured concentration respected the lower limit of 90% of the initial concentration. Containers were stored at -20±5°C, +5±3°C and +25±2°C with 60±5% relative humidity in a dark closed enclosure.
RESULTS
Stability was successfully maintained for every concentration and container tested when stored at -20±5°C and +5±3°C. In these storage conditions, particle contamination, pH monitoring and sterility assay respected the required criteria. Chemical degradation and colouring of solutions appeared before the end of the 1 year study period for most norepinephrine solutions stored at room temperature.
CONCLUSIONS
Ready-to-use solutions containing 0.2 and 0.5 mg/mL norepinephrine in polypropylene syringes or cyclic olefin copolymer vials must be stored at refrigerated or frozen temperatures to obtain acceptable 1 year shelf-stability. Exposure to higher temperatures significantly decreases shelf-stability. Our study protocol for compounding polypropylene syringes and cyclic olefin copolymer vials containing norepinephrine is adapted to implementation in centralised intravenous additive services.
Topics: Drug Compounding; Drug Stability; Drug Storage; Humans; Norepinephrine; Pharmaceutical Solutions; Time Factors
PubMed: 32296514
DOI: 10.1136/ejhpharm-2019-002146 -
Pharmaceutical Development and... 2016MJC13, a novel FKBP52 targeting agent, has potential use for the treatment of castration-resistant prostate cancer. The purpose of this work was to develop a solution...
MJC13, a novel FKBP52 targeting agent, has potential use for the treatment of castration-resistant prostate cancer. The purpose of this work was to develop a solution formulation of MJC13, and obtain its efficacy profile in a human prostate cancer xenograft mouse model. Preformulation studies were conducted to evaluate the physicochemical properties. Co-solvent systems were evaluated for aqueous solubility and tolerance. A human prostate cancer xenograft mouse model was established by growing 22Rv1 prostate cancer cells in C.B-17 SCID mice. The optimal formulation was used to study the efficacy of MJC13 in this preclinical model of castrate-resistant prostate cancer. We found that MJC13 was stable (at least for 1 month), highly lipophilic (logP = 6.49), poorly soluble in water (0.28 µg/mL), and highly plasma protein bound (>98%). The optimal formulation consisting of PEG 400 and Tween 80 (1:1, v/v) allowed us to achieve a MJC13 concentration of 7.5 mg/mL, and tolerated an aqueous environment. After twice weekly intratumoral injection with 10 mg/kg MJC13 in this formulation for four consecutive weeks, tumor volumes were significantly reduced compared to vehicle-treated controls.
Topics: Anilides; Animals; Antineoplastic Agents; Cell Line, Tumor; Chemistry, Pharmaceutical; Cyclohexanes; Disease Models, Animal; Humans; Injections, Intralesional; Male; Mice; Mice, SCID; Pharmaceutical Solutions; Prostatic Neoplasms, Castration-Resistant; Rats; Treatment Outcome; Xenograft Model Antitumor Assays
PubMed: 25380396
DOI: 10.3109/10837450.2014.979946