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The efficient synthesis of L-[5-11C]leucine and L-alfa-[5-11C]methylleucine has been investigated using a continuous two-step sequence of rapid reactions consisting of Pd0-mediated 11C-methylation and microfluidic hydrogenation. The synthesis of L-[5-11C]leucine and L-alfa-[5-11C]methylleucine was accomplished within 40 min with a decay-corrected radiochemical yield of 15-38% based on [11C]CH3I, radiochemical purity of 95-99%, and chemical purity of 95-99%. The Pd impurities in the injectable solution measured using inductively coupled plasma mass spectrometry met the international criteria for human use. Positron emission tomography scanning after an intravenous injection of L-[5-11C]leucine or L-alfa-[5-11C]methyl leucine in A431 tumor-bearing mice was performed. As a result, L-alfa-[5-11C]methylleucine was found to be a potentially useful probe for visualizing the tumor. Tissue distribution analysis showed that the accumulation value of L-alfa-[5-11C]methylleucine in tumor tissue was high [12 ± 3% injected dose/g tissue (%ID/g)].

Objective: Immediate-release (IR) oxycodone formulations may be manipulated for nonoral routes of administration. Oxycodone abuse-resistant immediate-release (ARIR) is a novel abuse-deterrent formulation (ADF) of IR oxycodone. This study aimed to assess the intravenous (IV) abuse potential of Oxycodone ARIR relative to commercially available IR oxycodone tablets using in vitro laboratory studies. Design: Intact or manipulated tablets were incubated in 5 or 10 mL of room temperature water for increasing amounts of time. For each timepoint, syringeability, defined as the ability to draw up water-immersed intact or manipulated tablets into a syringe, was assessed on a scale of 1 (very easy) to 10 (impossible). If the prepared sample could be drawn into a syringe, the proportion of syringeable oxycodone was measured analytically. Results: In all conditions, it was nearly impossible to draw any liquid into a syringe from samples containing manipulated Oxycodone ARIR tablets (N = 5/ group), and most samples released very low concentrations (

A new method for detecting and characterizing nanoparticles in an injectable pharmaceutical solution is presented. The method is based on the simultaneous use, on those nanoparticles that are crystalline, of three-dimensional electron diffraction tomography and energy dispersive X-ray spectrometry. With three-dimensional electron diffraction tomography, the unit cell and the crystal symmetry of the nanoparticles are determined, while with energy dispersive X-ray spectrometry, the chemical composition is derived. With these data, through an inspection of a crystallographic database, it is possible to determine the crystal phase of the nanoparticles. The knowledge of the crystal phase is a valuable element for understanding the provenance and the formation of the nanoparticles, helping the researcher in solving any quality control issue related to the presence of nanoparticles in an injectable solution.

Purpose. The research is devoted to the experimental choice of injection composition for auger technology of installation of underground anti-filtration shields under the source of pollution. The auger technology for the arrangement of an anti-filtration shield consists of pilot holes made by the horizontal directional drilling, which is followed by the arrangement of a waterproof layer by replacing the soil with auger by special concrete solution. Methodology. The main research method is experimental-statistical modeling, which includes conducting laboratory tests; correlation-regression analysis of the obtained data; qualitative, quantitative and graphical analysis of the obtained regularities of the studied indicators change from the varied factors. Findings. The main results of the study are the following: substantiation of the relevance of the development of the auger technology for the protection of underground space; development of methods and conducting laboratory experiments in choosing the injectable solution; analysis of experimental and statistical regularities of changes in water absorption and time of plastic strength setting when varying the composition of the anti-filtration shield (concentration of fiber, bentonite, water glass); development of the concept of technology of the anti-filtration shield arrangement. Originality. Experimental studies made it possible to establish that the minimum water absorption of the shied samples is observed at the lowest concentration of fiber (0.5%), bentonite (1%) and liquid glass (2%) in the injected solution. For structures of small width (1020m), there are suitable compositions with a minimum time of plastic strength setting at a concentration of fiber (3%), bentonite (5%) and water glass (18%). For structures with a large width (4060m), there are suitable compositions with a long time of plastic strength at a concentration of fiber (9%), bentonite (5%) and water glass (6%). Practical value. Experimental results made it possible to develop technological recommendations for construction of anti-filtration shields using the auger technology. Namely: to develop a concept and procedure of works, to calculate the costs of labor and machine time, to compile a list of necessary materials, machinery and equipment.

Vincristine (VCR), a naturally occurring vinca alkaloid, has received significant attention in recent years due to its vast therapeutic applications in the management of several types of cancer such as acute myeloid leukemia, acute lymphocytic leukemia, neuroblastoma, and small cell lung cancer. It is used as a unique component in several polychemotherapy combinations due to its unique clinical properties including lack of bone marrow suppression at the recommended dose. However, the narrow therapeutic index due to the dose-limiting irreversible neurotoxicity is hindering its immense potential. A conventional dosage form as an injectable solution has been successful to some extends, overcoming the challenges faced in developing an effective formulation. Recently, nanotechnology-based formulations are being looked on as a novel method for improving the pharmacokinetic properties, as well as enhancing the targetability of VCR. This review summarizes the therapeutic potential of VCR, explores its mechanisms of action, and discusses the success and challenges of VCR liposomes as well as nanoparticles in the past decade. This review also covers the potential techniques to improve the performance of VCR nanoformulations, thereby enhancing its clinical potential.

trans-Resveratrol, a phytochemical compound with antioxidant power and various therapeutic effects, such as cardioprotective, chemopreventive, and neuroprotective, among others, has disadvantages of poor solubility and limited stability, creating difficulties for the development of new strategies for its quantification. This study developed and validated an analytical stability method for trans-resveratrol by high-pressure liquid chromatography with photodiode-array detection (HPLC-PDA), which allowed its quantification in the presence of its degradation products. The quantification of trans-resveratrol occurred at a retention time of 2.6 min, with ammonium formate (10 mM, pH = 4)/acetonitrile, 70/30 v/v, as mobile phase. The validation met the ICH Q2 criteria of specificity, method linearity (2.8–4.2 μg/ml), precision and accuracy, robustness, quantification limit (0.176 μg/ml), and detection (0.058 μg/ml). As degradation products, cis-resveratrol was observed at 3.9 min, which could be resveratrone in 3.2 min and five unidentified products in 0.7, 1.0, 1.4, 1.8, and 5 min. Some solutions subjected to temperature stress of 40 and 60°C, UV light, and acidic and basic hydrolysis exhibited colour changes. An analytical method was obtained by HPLC-PDA, which allowed quantifying the stability of trans-resveratrol in a fast and specific manner in the presence of its degradation products.

Anaplasma marginale is a gram-negative rickettsial pathogen that can cause clinical anemia and death in cattle. The objective of this study was to evaluate the effectiveness of enrofloxacin (ENR) 100 mg/mL at a single subcutaneous dose of 5.7 mg/lb (12.5 mg/kg) for treatment of acute anaplasmosis (ANA) in mature beef cows (n=67). Following intravenous inoculation with A. marginale-infected blood, cattle were monitored for clinical signs of ANA. Upon meeting case criteria, cattle were randomly assigned to receive ENR or saline (SAL). Treatment success, defined as 28 d post-treatment survival and resolution of abnormal clinical scores, was 81.8% (27/33) and 44.1% (15/34) (P=0.0032) for ENR and SAL treated cows, respectively. Mortality was 47% (16/34) and 3% (1/33) in SAL and ENR, respectively (P=0.0027). Packed cell volume at 7, 14, 21, and 28 d post-treatment was significantly greater in ENR compared to SAL (P, The Bovine Practitioner, Vol. 54, No. 1 (2020 Spring)

RESUMEN Antecedentes: España por su situación geopolítica no está exenta de amenazas y desafíos asociados a enfermedades infecciosas víricas como las «fiebres hemorrágicas víricas». Implementar acciones para disminuir estos riesgos frente a agentes víricos con el desarrollo de un tratamiento de urgencia por vía intravenosa resulta de gran interés. Objetivos: Desarrollar dos formulaciones de Ribavirina 100 mg/ml con distintos excipientes y condiciones de fabricación para buscar la formulación más estable. Material y métodos: Se ha utilizado ribavirina, distintos tampones y agua para inyectables. Se ha evaluado alteraciones físicas, riqueza y pH siguiendo especificaciones de la monografía de la Farmacopea Europea. Resultados: Se exponen resultados de pH y riqueza de ambas formulaciones con y sin esterilización terminal. Conclusiones: Los resultados obtenidos cumplen especificaciones para ambas formulaciones, demostrando una estabilidad química tras su conservación en condiciones de estudios a largo plazo durante 12 meses y acelerados durante 6 meses. El desarrollo de la ribavirina 100 mg/ml (10% w/v) inyectable satisface una necesidad terapéutica relacionada con el tratamiento de primera elección en enfermedades víricas altamente contagiosas que carecen de tratamientos eficaces. SUMMARY Background: Spain, due to its geopolitical situation, is not exempt from the threats and challenges associated with viral infectious diseases such as the «viral hemorrhagic fevers». Implementing actions to reduce these risks with the development of an emergency treatment against these viral agents for intravenous is of great interest. Objective: Develop two formulations of Ribavirin 100 mg/ml with different excipients and manufacturing conditions to look for the most stable formulation. Material and methods: Ribavirin, various buffers and water for injections have been used. Physical alterations, richness and pH have been evaluated following specifications of European Pharmacopoeia monograp. Results: Results of pH and richness of both formulations are exposed with and without terminal sterilization. Conclusions: The results obtained meet specifications for both formulations, demonstrating chemical stability after preservation under long-term study conditions for 12 months and accelerated for 6 months. The development of injectable 100 mg/ml ribavirin (10% w/v) satisfies a therapeutic need related to the treatment of first choice in highly contagious viral diseases that lack treatments.

Background: A simple, eco-friendly and low-cost Infrared (IR) method was developed and validated for the analysis of Cefepime Hydrochloride (CEF) in injectable formulation. Different from some other methods, which employ organic solvents in the analyses, this technique does not use these types of solvents, removing large impacts on the environment and risks to operators. Objective: This study aimed at developing and validating a green analytical method using IR spectroscopy for the determination of CEF in pharmaceutical preparations. Methods: The method was validated according to ICH guidelines and the quantification of CEF was performed in the spectral region absorbed at 1815-1745 cm-1 (stretching of the carbonyl group of β- lactam ring). Results: The validated method showed to be linear (r = 0.9999) in the range of 0.2 to 0.6 mg/pellet of potassium bromide, as well as for the parameters of selectivity, precision, accuracy, robustness and Limits of Detection (LOD) and Quantification (LOQ), being able to quantify the CEF in pharmaceutical preparations. The CEF content obtained by the IR method was 103.86%. Conclusion: Thus, the method developed may be an alternative in the quality control of CEF sample in lyophilized powder for injectable solution, as it presented important characteristics in the determination of the pharmaceutical products, with low analysis time and a decrease in the generation of toxic wastes to the environment.

The aim of the present study was to assess the antipyretic activity of the macrolide antibiotic, tilmicosin, at dose levels of 20 and 40 mg/kg of body weight, subcutaneously, in Brewer's yeast-induced fever model in mice. Pyrexia was induced by subcutaneous injection of 20 mL/kg of 20% (w/v) Brewer’s yeast suspension into the animal’s scruff region. Eighteen hours later, feverish animals were treated with either tilmicosin or acetylsalicylic acid (200 mg/kg injectable solution, subcutaneously) or vehicle; and rectal temperatures were evaluated at 1, 2, 3, 4 and 5 h post-treatment using digital thermometers. Tilmicosin showed dose-dependent significant decrease in the elevated body temperature of mice that remained sustained throughout the tested time points from 1 to 5 h in the used model. Both small and large dose levels showed a significant inhibition of elevated body temperature when compared with the corresponding febrile controls (37.65 ± 0.04 vs. 38.41 ± 0.08°C and 37.44 ± 0.04 vs. 38.44 ± 0.04, after 1 h; 37.19 ± 0.04 vs. 38.41 ± 0.08°C and 36.80 ± 0.03 vs. 38.44 ± 0.04°C after 5 h, respectively). These activities were standardized as 38.0 and 51.59% and 47.9 and 66.43% after 5 h, respectively, compared to that of the standard antipyretic and acetylsalicylic acid (200 mg/kg of body weight, subcutaneously). These results may indicate that tilmicosin, in addition to its well established antibacterial activity, possesses significant antipyretic activity that may be beneficial in symptomatic relief when it is used in therapy of infectious disease conditions and inflammatory disorders. Key words: Antipyretic, tilmicosin, macrolides.

Imaging prostate-specific membrane antigen (PSMA) using positron emission tomography (PET) has been presented so far as the most sensitive and specific with regard to prostate cancer detection, in particular in high-risk prostate cancer patients. Currently, it mainly features Gallium-68 ( 68 Ga) labeled PSMA ligands, notably [ 68 Ga]Glu-urea-Lys(Ahx)-HBED-CC ([ 68 Ga]-PSMA-11) and [ 68 Ga]DOTAGA-FFK (Sub-KuE termed ([ 68 Ga]PSMA-I&T). However, 68 Ga has several shortcomings as radionuclide including a short half-life and non-ideal energies. This has motivated consideration of 18 F-labeled analogues for PET imaging of prostate cancer. Here, we describe a simple synthesis and validation of a fluorine-18 labeled Glu-urea-Lys(Ahx)-HBED-CC ([Al 18 F]PSMA-11) for nuclear medicine applications. An efficient method for preparation of [Al 18 F]PSMA-11 was developed and validated (according to Pharm Eur) for routinely clinical applications. [Al 18 F]PSMA-11 was reproducibly obtained in radiochemical yields of 84 ± 6% (n = 15) and > 98% radiochemical purity using an improved one-step radiofluorination in aqueous solution. The total (production/preparation) time, including purification, pharmacological formulation of the isolated product and the quality control of the injectable solution was less than 60 min. The [Al 18 F]PSMA-11 was stable over 4 h in 1% EtOH/saline selected as injection solution. The solution was sterile, non-pyrogenic and ready for clinical applications after sterile filtration through a 0.22 µm membrane filter under sterile conditions. In addition, [Al 18 F]PSMA-11 exhibited higher uptake and retention in PMSA-expressing LNCap prostate cells as compared to its clinically established 68 Ga-labeled analogues [ 68 Ga]PSMA-11 and [ 68 Ga]PSMA-I&T as well as to [ 68 Ga]NOTA-Bn-PSMA. The simple and fast preparation of [Al 18 F]PSMA-11 combined with its favorable pharmacological properties warrant its translation to a clinical setting. Conclusion The facile and high-yielding radiosynthesis of [Al 18 F]PSMA-11as well as its promising in vitro and in-vivo characteristics makes it worthy of clinical development for PET imaging of prostate cancer.

The risk of consuming marketed milk containing Chloramphenicol (CAP) residues was investigated by testing 41 dairy milk samples collected at retail outlets of farms at Dakar (Senegal) from March to November 2013. Analysis for CAP residues was performed at the Veterinary Drugs Control Laboratory (LACOMEV) of the Inter-States School of Veterinary Sciences and Medicine (EISMV) of Dakar using reverse-phase HPLC with UV/Visible detection at 278 nm. The results showed that 78.04% of marketed milk samples contained CAP drug residues suggesting that this veterinary drug is used in dairy cows in Senegal even though it is not approved in food producing animals. Investigations on veterinary drugs importations have showed that 82.82% of powders for injectable solution were associated with CAP while this compound was included in 27.32% of other solid tetracycline formulations. Although this pilot study is not representative of the general situation, the findings are alarming and reflect a misuse of antibiotics in dairy farms in Senegal.

The combination of the powerful antimicrobial agent florfenicol and the nonsteroidal anti-inflammatory flunixin meglumine is used for the treatment of bovine respiratory disease (BRD) and control of BRD-associated pyrexia, in beef and nonlactating dairy cattle. This study describes the development and validation of an HPLC-UV method for the simultaneous determination of florfenicol and flunixin, in an injectable preparation with a mixture of excipients. The proposed RP-HPLC method was developed by a reversed phase- (RP-) C18e (250 mm × 4.6 mm, 5 μm) column at room temperature, with an isocratic mobile phase of acetonitrile and water mixture, and pH was adjusted to 2.8 using diluted phosphoric acid, a flow rate of 1.0 mL/min, and ultraviolet detection at 268 nm. The stability-indicating method was developed by exposing the drugs to stress conditions of acid and base hydrolysis, oxidation, photodegradation, and thermal degradation; the obtained degraded products were successfully separated from the APIs. This method was validated in accordance with FDA and ICH guidelines and showed excellent linearity, accuracy, precision, specificity, robustness, LOD, LOQ, and system suitability results within the acceptance criteria.

Heparin is a naturally occurring, highly sulfated polysaccharide that plays a critical role in a range of different biological processes. Therapeutically, it is mostly commonly used as an injectable solution as an anticoagulant for a variety of indications, although it has also been employed in other forms such as coatings on various biomedical devices. Due to the diverse functions of this polysaccharide in the body, including anticoagulation, tissue regeneration, anti-inflammation, and protein stabilization, and drawbacks of its use, analogous heparin-mimicking materials are also widely studied for therapeutic applications. This review focuses on one type of these materials, namely, synthetic heparin-mimicking polymers. Utilization of these polymers provides significant benefits compared to heparin, including enhancing therapeutic efficacy and reducing side effects as a result of fine-tuning heparin-binding motifs and other molecular characteristics. The major types of the various polymers are summarized, as well as their applications. Because development of a broader range of heparin-mimicking materials would further expand the impact of these polymers in the treatment of various diseases, future directions are also discussed.

BACKGROUND: Enoxaparin is often diluted to accurately deliver doses to neonatal and infant patients. Current recommendations for dilutions may not be adequate for the smallest patients.METHODS: Review of dosing at our institution occurred, and an 8 mg/mL concentration of enoxaparin was chosen. A concentration of 8 mg/mL was compounded by diluting 0.4 mL of enoxaparin (100 mg/mL) into 4.6 mL of sterile water for injection into an empty sterile vial. Four syringes of the 8 mg/mL concentration were prepared by 5 technicians (20 total syringes). Stability and sterility testing occurred a 0, 7, 14, and 30 days. One-way repeated-measures analysis of variance was used to detect significant differences in Anti–Factor Xa concentrations at the testing time points.RESULTS: The dilution of enoxaparin was sterile at 30 days but exhibited significant degradation at the 30-day point (p < 0.05).CONCLUSION: A dilution of enoxaparin 8 mg/mL is stable and sterile for 14 days refrigerated but is not stable at 30 days.

strip foundation of the existing building, adjacent slab foundation, strip foundation increment of settlement, metal sheet piling, geotechnical barrier, the weak clay base In the Kuban State Agrarian University are conducted a study on assessment of works of separating barriers in weak clay soils, arranged to protect the existing buildings on the impact of the new building. To reduce the development of additional settlement strip foundations of the existing building on the influence of pressure, transmitted to the ground situated close to the new slab foundation, considered two options for separating barriers. In first variant separating barrier made of a metal sheet pile Larsen. Under the terms of the task are believed that the metal sheet piling dipped into the ground indentation (or vibro) to excavation opening a new building. Sheet piling length is assigned by calculation or constructively, often under the assumption that the entire thickness cutting through weak clay soils. It was found that the best results are achieved in the metal sheet pile when it based in the lower end of the ground low compressibility. In a second embodiment of separating barrier made of geotechnical (grouting) barriers. Under the terms of the task is believed that prior to the start of major construction works originally produced by cementation of soil injectors (soil preparation), in which filled all the cavities, cracks, zones of low density at the bottom. Thus, there is a compaction and reinforcement of soil lenses cement grout and create a more rigid structure that can respond to a further injection of an injectable solution. According to the results of the calculations and modeling determined that the greatest positive effect on the separating wall foundations is achieved when it is arranged as a geotechnical barrier. Additional settlement strip foundation of an existing building has decreased to 60–65 % (about 4,2 cm) as compared with 8,5 cm additional settlement, which will be in the absence of separating barrier. If the separating barriers between the foundation of the building is used a metal sheet piling Larsen, an additional strip foundation settlement will also be reduced, but only by 20–25 % and will amount to about 6,8 cm.

Cephalothin is a first-generation cephalosporin, that shows great activity against Gram-positive microorganisms. Its effect is bactericidal, and due its action, it is the most efficient first-generation cephalosporin against resistant microorganism (β-lactamase producers). Although this drug has been clearly studied and researched about its antimicrobial activity, pharmacokinetics and pharmacodynamics, there are a few studies in literature regarding the development of analytical methodology for this cephalosporin. The aim of this work was to develop and validate a new method of analysis, using high performance liquid chromatography, resulting in an innovative method, quick and using solvents of low toxicity, minimizing, in this way, its toxic actions to the operators and leavings in the environment. The method developed and validated for the quantification of sodium cephalothin in lyophilized powder for injectable solution used high performance liquid chromatography (HPLC). The mobile phase consisted in water with 0.7% of glacial acetic acid and ethanol (70:30 v/v), wave-length of 237 nm, Zorbax Eclipse Plus C18 AgilentTM column and room temperature of 25°C, retention time of 4,20 minutes. The method was linear in the concentrations of 20, 40, 60, 80 e 100 μg/mL, selective, accurate and robust towards these modifications: ethanol brand, water source, mobile phase rate, glacial acetic acid proportion, flow rate, room temperature and wave length. The dosing for CET was of 106.72%.

A fentanila é um fármaco analgésico de uso hospitalar principalmente indicado como componente da anestesia. Devido a uma queixa técnica de um hospital de São Paulo apontando a ineficácia terapêutica de uma solução injetável de citrato de fentanila após o uso na anestesia, amostras do produto foram colhidas pela vigilância sanitária para análise. O objetivo deste trabalho foi realizar ensaios físico-químicos nas amostras, com prioridade para identificação e teor do fármaco, utilizando-se um cromatógrafo líquido de alta eficiência equipado com detector de arranjo de diodos. Os dois lotes analisados apresentaram identificação positiva para citrato de fentanila e 97,30% do teor declarado do fármaco; resultados satisfatórios em relação ao especificado pelo fabricante do produto. Assim, foi possível excluir desvios no teor do fármaco como a causa da ineficácia terapêutica, indicando a necessidade de investigações complementares e levantando maiores discussões sobre o caso.

DanHong injection is a Danshen (Salvia miltiorrhiza roots)-based injectable solution for treatment of coronary artery disease and ischemic stroke. Danshen catechols are believed to be responsible for the injection's therapeutic effects. This study aimed to characterize systemic exposure to and elimination of Danshen catechols in human subjects, rats, and dogs receiving intravenous DanHong injection. A total of 28 catechols were detected, with content levels of 0.002-7.066 mM in the injection, and the major compounds included tanshinol, protocatechuic aldehyde, salvianolic acid B, rosmarinic acid, salvianolic acids A and D, and lithospermic acid with their daily doses ≥10 μmol/subject. After dosing, tanshinol, salvianolic acid D, and lithospermic acid exhibited considerable exposure in human subjects and rats. However, only tanshinol had considerable exposure in dogs. The considerable exposure to tanshinol was due to its having the highest dose, whereas that to salvianolic acid D and lithospermic acid was due to their relatively long elimination half-lives in the human subjects and rats. Protocatechuic aldehyde and rosmarinic acid circulated in the bloodstream predominantly as metabolites; salvianolic acids A and B exhibited low plasma levels with their human plasma metabolites little or not detected. Tanshinol and salvianolic acid D were eliminated mainly via renal excretion. Elimination of other catechols involved hepatobiliary and/or renal excretion of their metabolites. Methylation was found to be the primary metabolism for most Danshen catechols and showed intercompound and interspecies differences in rate and degree in vitro. The information gained here is relevant to pharmacological and toxicological research on DanHong injection.

Проведено аналіз літературних джерел з питання застосування імуностимуляторів в ветеринарній практиці. Зазначено, що на сучасному фармацевтичному ветеринарному ринку існують імпортні високовартісні препарати. За мету було поставлено створення оригінального вітчизняного лікарського засобу для боротьби з вірусними інфекціями тварин. Проведено технологічні дослідження імуностимулюючого засобу для посилення специфічної імунопрофілактики сільськогосподарської птиці 1 % ін’єкційного розчину Авесстим, розроблено технологічну схему виробництва даного лікарського засобу в ампулах

Made available in DSpace on 2018-12-11T17:33:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-08-01 Cefazolin sodium (CFZ) is a semi-synthetic first-generation cephalosporin used for the treatment of infections caused by Gram-positive and Gram-negative microorganisms. Although it is a drug used worldwide, there are only a few green analytical methods described in the literature for its quantification. This work proposes an eco-friendly, low-cost, and rapid analytical method to analyze CFZ in lyophilized powder for injectable solution based on digital images, using thin-layer chromatography (TLC). For the TLC method, the mobile phase was comprised of ethanol and water, and the spots revelation was performed using iodine vapors. The TLC spots were analyzed through digital images, obtained by flatbed scanner, and evaluated using the free software The Gimp (GNU Image Manipulation Program), by quantification of pixels in pictures. This method was validated according to the International Conference on Harmonization (ICH) guidelines and presented adequate linearity, accuracy, precision, and robustness. It also showed its selectivity and stability-indicating capability (under acid, alkaline, aqueous, oxidative, and photolytic stress conditions). This is an innovative, easy, and low-cost method that can be used for the analysis of cefazolin sodium in lyophilized powder. Considering that this method does not use toxic organic solvents for the environment and operators, it contributes to the development of green chemistry. Institute of Biochemistry and Biotechnology Faculty of Natural Science I Martin-Luther-University Halle-Wittenberg Department of Pharmaceutics School of Pharmaceutical Sciences of Araraquara Universidade Estadual Paulista - UNESP Department of Pharmaceutics School of Pharmaceutical Sciences of Araraquara Universidade Estadual Paulista - UNESP

Short-lived radiolabeled tracers for positron emission tomography (PET) must be rapidly synthesized, purified, and formulated into injectable solution just prior to imaging. Current radiosynthesizers are generally designed for clinical use, and the HPLC purification and SPE formulation processes often result in a final volume that is too large for preclinical and emerging in vitro applications. Conventional technologies and techniques for reducing this volume tend to be slow, resulting in radioactive decay of the product, and often require manual handling of the radioactive materials. We present a fully-automated microfluidic system based on sweeping gas membrane distillation to rapidly perform the concentration and formulation process. After detailed characterization of the system, we demonstrate fast and efficient concentration and formulation of several PET tracers, evaluate residual solvent content to establish the safety of the formulated tracers for injection, and show that the formulated tracer can be used for in vivo imaging.

Background: An innovative injectable solution containing low molecular hyaluronic acid (HA) and a specific Amino Acids mixture was formulated to physiologically promote local neo-collagenesis and elastogenesis through fibroblasts chemotaxis migration into the injected area. Objective: Aim of this open clinical trial is to evaluate efficacy and tolerance of the injectable product under study, on main sign of face skin photoaging. Methods: A single Italian center treated 25 female subjects aged 48-65 years with 4 micro-injection sessions with 10-day time laps between each product administration. Subjects were evaluated in basal conditions and after 4, 8, 12 and 24 weeks, using validated clinical scales, subjective evaluations and objective quantitative outcome measures. Assessment of aesthetic results included photographic documentation. Results: Obtained results showed an improvement of all the clinical and subjective assessments and on the majority of objective instrumental parameters. These were already significant 10 days after the first injection procedure and were still significant and still improving after 6 months (at follow up). Global judgment on tolerability was good/excellent, both in the investigators’ opinion and volunteers’ self-evaluation. Conclusions: Obtained results confirm the aesthetic performance of the injectable product on main signs of face skin photoaging. In particular, it was demonstrated the biovolumetric effect, the antiwrinkle efficacy, a superficial and deep moisturising activity and elasticizing properties. This study supports the definition of extracellular matrix targeting (ECM-targeting) for this product.

Alendronate sodium (ALD) is a second generation amino bisphosphonate that use for treatment of bone diseases. Since ALD is poorly absorbed from the gastrointestinal tract and its absorption is markedly reduced by food, the aim of this study is to evaluate the bone uptake of ALD through vaginal route. To evaluate the bone uptake of ALD by gamma scintigraphy, ALD was radiolabeled with Technetium-99 m ( 99m Tc). Vaginal supposi-tories and injectable solution of 99m Tc-ALD was prepared and gamma scintigraphy studies were performed with intravaginally and intravenously 99m Tc-ALD applied rabbits. The results were revealed that ALD was successfully labeled with 99m Tc. After intravaginal and intravenous application, 99m Tc-ALD showed a high uptake in bone. Despite accumulation times and uptake ratios showed differences between administration routes, our preliminary observations suggest that the intravaginal route appears to be a viable alternative for ALD application and should be evaluated in future clinical studies.

The aim of this work was to identify the main sources of uncertainty, quantify the standard deviation of each source of uncertainty, and calculated combined and expended uncertainties for the determination of linezolid in injectable dosage forms by UV spectrophotometry. The contributions of precision, linearity and weight of linezolid reference standard are the most significant, contributing with about 77% of the overall uncertainty. The uncertainties on the absorbances (sample and standard), volumetric flasks and volumetric pipettes have virtually no influence on the overall uncertainty. The estimated uncertainty of the spectrophotometric method for determination of linezolid was adequate for the scope of the method.

Purpose The aim of the present study was to evaluate the acute toxicity and pharmacokinetics of paclitaxel nanosuspensions stabilized with TPGS in mice. Method The paclitaxel nanosuspensions were prepared by evaporative precipitation into aqueous solution (EPAS) method, and freeze-dried powders of the nanosuspensions were obtained through lyophilization process. The morphology and particle size of nanosuspensions were determined by transmission electron microscope and Zetasizer, respectively. The acute toxicity and pharmacokinetics of paclitaxel nanosuspensions after intravenous administration to Kunming mice were studied. A marketed paclitaxel injectable solution was studied parallelly. Results The paclitaxel nanoparticles were in rod shape under transmission electron microscope, and their mean particle size was 135.4 ± 5.7 nm. Results of acute toxicity showed the LD 50 of paclitaxel nanosuspensions was 98.63 mg/kg, twice more than that of the marketed injection (41.46 mg/kg). After intravenous injection paclitaxel nanosuspensions displayed different pharmacokinetic properties in comparison with the marketed injectable solution, including a decreased initial drug concentration, increased plasma half-life, AUC and MRT. Conclusions The paclitaxel nanosuspensions prepared in this study could markedly enhance the tolerance dosage in mice, and manifest different pharmacokinetic properties compared with the solution.

A downscaled analytical HPLC purification strategy for [(11)C]raclopride and [(11)C]DASB was proposed to obtain a straightforward produced injectable solution with a substantially reduced volume. Both tracers were radiosynthesized using [(11)C]methyl triflate, and several analytical columns, in combination with ethanol containing eluents, were examined to optimize the chromatographic resolution. This resulted in a 5 mL solution of [(11)C]raclopride, obtained after 6 min, and a 7 mL solution of [(11)C]DASB, obtained after 10 min, using a C16-alkylamide and CN column respectively.

New formulation of Ivermectin 1% injectable solution was prepared for Veterinary therapeutic use. Information about all the materials used in preparation of formula were collected from the pharmacopeia while analar material were provided and used to prepare about three pilot formulae, from which the final one was prepared. Stability of new formula was tested in different room environmental conditions by comparing any change in physicochemical properties concerning form, color, transparency, pH in different storage room temperatures for 20 months. The results of testing the formula both in-vitro against parasitic larvae motility and parasitic infection in diseased cattle and sheep indicating its efficiency as well as its chemical analysis, that indicate nearly no change in its concentrations for almost two years analysis. This formula was approved by I.V.S.C. as a drug for veterinary therapeutic uses after passing all testing schedule. A certificate for such was provided

BACKGROUND Radiopaque markers and soft tissue models have been used extensively in clinical applications to target cancerous lesions and to calibrate and characterize imaging systems. However, the development of radiopaque, soft tissue models for pulmonary lesions is yet to be optimized. Such a material may improve endoscopic training techniques and also be useful to evaluate bronchoscopy navigation systems by the targeting and sampling of tumor models with computed tomography. METHODS This study investigates a modified agarose-based model and a novel contrast-infused tripe model to create clinically relevant pulmonary tumor models. An iodine-enhanced agarose model presents an injectable solution with high image contrast under computed tomography capable of reaching distal bronchial airways. The tripe solution presents a cheap and easily deployed method to quickly establish a fiducial marker that may be used during bronchial imaging system training and evaluation. RESULTS The iodine-enriched agarose model demonstrates desirable mechanical characteristics ex vivo, but has a number of limitations when administered in a live setting. The tripe solution presents a far more effective in vivo pulmonary tumor model and offers an effective radiopaque marker. However, the size of the tripe tumor samples required for effective insertion limits its ability to reach more distal airways. An iterative testing process was used to optimize the model composition, culminating in live animal investigations (n=3). CONCLUSION Both contrast-infused agarose and tripe models present a promising analog to a pulmonary lesion and may act as a radiopaque marker for bronchoscopic training and biopsy evaluation.

Introduction The purpose of this study was to investigate the quality of a select group of medicines sold in accredited drug dispensing outlets (ADDOs) and pharmacies in different regions of Tanzania as part of an in-depth cross-sectional assessment of community access to medicines and community use of medicines. Methods We collected 242 samples of amoxicillin trihydrate, artemether-lumefantrine (ALu), co-trimoxazole, ergometrine maleate, paracetamol, and quinine from selected ADDOs and pharmacies in Mbeya, Morogoro, Singida, and Tanga regions. The analysis included physical examination and testing with validated analytical techniques. Assays for eight of nine products were conducted using high-performance thin-layer chromatography (HPTLC). For ALu tablets, we used a two-tiered approach, where tier 1 was a semi-quantitative Global Pharma Health Fund-Minilab® method and tier 2 was high-performance liquid chromatography (HPLC) as described in The International Pharmacopoeia’s monograph for artemether-lumefantrine. Results and Discussion The physical examination of samples revealed no defects in the solid and oral liquid dosage forms, but unusual discoloration in an injectable solution, ergometrine maleate. For ALu, the results showed that of 38 samples, 31 (81.6%) passed tier 1 testing and 7 (18.4%) gave inconclusive drug content results. The inconclusive ALu samples were submitted for tier 2 testing and all met the quality standards. The pass rate using the HPTLC and TLC/HPLC assays was 93.8%; the failures were the ergometrine maleate samples purchased from both ADDOs and pharmacies. The disintegration testing of the solid dosage forms was conducted in accordance with US Pharmacopeia monographs. Only two samples of paracetamol, 1.2% of the solid dosage forms, failed to comply to standards. The study revealed a high overall rate of 92.6% of samples that met the quality standards. Although the overall failure rate was 7.4%, it is important to note that this was largely limited to one product and likely due to poor distribution and storage rather than poor manufacturing practices. Conclusions Over 90% of the medicines sold in ADDOs and pharmacies met quality standards. Policy makers need to reconsider ergometrine maleate’s place on the list of medicines that ADDOs are allowed to dispense, by either substituting a more temperature-stable therapeutically equivalent product or requiring those sites to have refrigerators, which is not a feasible option for rural Tanzania.

The aim of this study was prepared new formulation of trimethoprim injectablesolution in the Physiology and pharmacology department /College ofVeterinaryMedicine, University of Baghdad.Trimethoprim injection formulation is antibacterial andused against a number of bacteria, protozoa and Rickettsia. Data was collected about thematerials used in the preparation of the formula from the well-known pharmacopeia,including the specification, physical and chemical properties of active ingredient, theadditive and preservative that must be used. Three pilot formulae were prepared fromanalar chemical ingredient from which one formula was chosen and tested to approve itsquantitative and qualitative specification. Quantitative evaluation, stability of theformula was also tested under different storage environmental condition of low and hightemperature at different periods through and one year and through the questionnaire field.Questionnaire proved the product, stability and therapeutic efficiency. The compositionobtained a certificate of acceptance from the Veterinary State Company and VeterinaryDrug Research and production Centre as new preparation Formula of TrimethoprimInjectable Solution for Veterinary use.

Preparation of a new formulation of oxytetracycline 20% injectable solution was done for veterinary therapeutic use. Information about all the materials used in preparation of formula were collected from the well known pharmacopeia while analar material were provided and used to prepare about three pilot formulae, from which the final one was prepared. Stability of new formula was tested in different room environmental conditions by comparing any change in physicochemical properties concerning form, colour, transparency, pH in different storage room temperatures for 18 months as well their MIC value and bacterial inhibition rate formorethan 12 months. The results showed that the new drug proved its stability, antibacterial activity when tested both in vitro against E coli 0.78 was growth in which MIC was 0.2 µ g /ml. It was also tested clinically in therapy of group of infected sheep and cows (4 each) with respiratory diseases, at the college of veterinary medicine, University of Baghdad as well as in the central veterinary hospital in comparison with other similarly infected group treated with common commercially used 20% oxytetracycline drug (Alamycin) ® while control group treated with normal saline. The results showed improvement of the animals of both treated groups when compared with control one, which its animal health deteriorated and improved when treated with the formula. Both quantitative and qualitative results for oxytetracycline 20% formula as well as its physicochemical properties and steritity was tested by Board of drug and biological standardization, Iraqi Veterinary State Company (I.V, S.C.) and a certificate of approval of quality, quantity, antibacterial activity was issued by I.V.S.C. for new oxytetracycline 20% injectable solution and registered, it as new drug formulated by the College of Veterinary Medicine, university of Baghdad for veterinary use.

Objectives The in-use stability study in this paper was designed as far as possible to simulate a practical usage of the multi-dose containers products in veterinary practice and an influence of storage conditions on quality of drug's active substance. Methods In-use stability testing of enrofloxacin (ENRO) as an active substance in Veterinary Medicinal Products (VMP's) was studied during a period of 115 days. Appropriate quantities of VMP's were removed by the withdrawal method regularly used and described in the product literature. The physical-chemical parameters and microbiological contamination in the multi-dose containers of injectable solutions of ENRO were assessed. The differences among various injectable solutions and differences among their batches and shelf-lives were analysed. A spectrophotometric method was modified and validated for quantification of ENRO in injectable solutions. Key findings The validation method yielded good results and included the selectivity, linearity, intra-assay precision (1.26 % RSD), inter- assay precision (1.52 % RSD), limit of detection (0.17 μg/mL), limit of quantification (0.57 μg/mL) and accuracy. Results of in–use stability testing on injectable solutions were presented as the mean drug concentration of ENRO vs. time of sampling. Conclusions ENRO assays of batches within proposed shelf-life (28 days) and batches out of proposed shelf-life were within producer's decelerated content and no extreme changes during prescribed storage were occurred. Study was extended from the drug's proposed shelf-life for next 87 days and in that period no significant changes of ENRO assay was occurred either.

Se describe el desarrollo de una formulación que contiene ribavirina como principio activo, a una concentración de 100 mg/mL que mantiene sus propiedades estables desde el punto de vista físico, químico y microbiológico. Se realizaron los estudios de formulación correspondientes con el objetivo de determinar la formulación idónea, el procedimiento tecnológico y el envase adecuado para garantizar la estabilidad del producto terminado. Se elaboraron 3 lotes del medicamento, los cuales se envasaron en bulbos incoloros de vidrio, con calidad hidrolítica I y se almacenaron a temperatura ambiente de 30 ± 2 °C durante 12 meses; se estudió su estabilidad física y química por el método acelerado y de vida de estante. Se comprobó su estabilidad microbiológica a través de un ensayo de esterilidad, a cada uno de los lotes elaborados, al inicio y final del estudio, según la Farmacopea de los Estados Unidos 30 y la regulación establecida por el Centro Estatal de Control de Medicamentos de Cuba; se obtuvieron resultados satisfactorios. Se realizó un estudio toxicológico del inyectable que mostró un amplio margen de seguridad para ser usado en humanos. Todos los resultados obtenidos cumplieron con los límites de calidad establecidos en la literatura oficial para este tipo de forma farmacéutica, por lo que se llegó a la conclusión que el medicamento desarrollado está correctamente formulado desde el punto de vista galénico con un tiempo de vida útil de 12 meses, almacenado bajo las condiciones estudiadas. Finalmente el medicamento fue introducido al nivel industrial sin que se presentaran problemas tecnológicos.Development of a formula containing Ribavirin as active principle at a 100 mg/mL concentration maintaining its stable properties from the physical, chemical and microbiological point of view is described. The aim of present formula studies was to determine the suitable formula, the technological procedure and the appropriate package to guarantee stability of end product. Three drugs batches were manufactured, which were packing in colourless glass bulbs with a hydrolytic I quality and stored at room temperature of 30 ± 2 ºC for 12 months; its physical and chemical was studied by accelerated method and shelf life. Its microbiological stability was verified by sterility trial in each of processed batches at study onset and at the end according to USA Pharmacopeia-30 and the regulation established by Cuban State Center for Drug Control with satisfactory results. A toxicology study was conducted of injectable agent showing a wide safety margin to human use. All results obtained fulfilled the quality limits established in official literature for this type of pharmaceutical way thus concluded that the developed drug is properly formulated from the medical point of view with a useful life time of 12 months, stored under study conditions. Finally, the drug was introduced at industrial level without technological problems.

Background:. The use of deoxycholic acid to reduce localized fat deposits is a procedure that has been in use for about 30 years. Its effectiveness as treatment is due to emulsification of phospholipids and therefore, solubilization of the biological membranes with resulting fat necrosis. The purpose of the study was to assess the effectiveness and the safety of an injectable solution containing sodium deoxycholtate 1.25% (DB125), used as intralipotherapy. Methods:. The effectiveness and safety of DB125 solution have been assessed with a multicentre observational prospective study carried out between February and October 2017. The 221 selected patients presented with various forms and degrees of localized fat in several areas. Intralipotherapy treatments were performed 6 weeks apart and until the clinical result was obtained. Aesthetic outcomes were evaluated by the authors using preoperative and postoperative photographic documentation and by the patients with their level of satisfaction by filling out an anonymous form. Major adverse events were reported by each doctor who performed the treatment. Results:. Two hundred twenty-one patients treated in 273 cases of different localized fat deposits. One hundred eighty-five patients who could be assessed for final results gave the effectiveness of the treatment an average score of 7.4. The failure percentage of the treatment was 3.8%. The medical evaluation showed treatment success in 93.5% of cases. Adverse events can be divided into 2 groups: minor adverse events, which are very frequent and major ones, which are extremely rare. For both groups, the adverse events can be ascribed to localized problems in the treatment area. Conclusion:. Studies have shown that the second-generation solution containing sodium deoxycholate 1.25% is effective and safe to treat different localized fat deposits. The high degree of effectiveness shown in the study was not associated with a lesser degree of handling because, at the doses indicated and with the use of intralipotherapy, the occurrence of adverse events was minimal.

Purpose: In the radionuclide treatment of some forms of brain tumors such as craniopharyngiomas, the selection of the appropriate radionuclide for therapy is a key element in treatment planning. The aim was to study the influence by considering the beta-emitter radionuclide dose rate in an intracranial cyst. Methods: Dosimetry was performed using the MCNP4C radiation transport code. Analytical dosimetry was additionally performed using the Loevinger and the Berger formulas in the MATLAB software. Each result was compared under identical conditions. The advantages and disadvantages of using {sup 90}Y versus {sup 32}P and {sup 186}Re were investigated. Results: The dose rate at the inner surface of the cyst wall was estimated to be 400 mGy/h for a 1 MBq/ml concentration of {sup 90}Y. Under identical conditions of treatment, the corresponding dose rates were 300 mGy/h for {sup 32}P and 160 mGy/h for {sup 186}Re. For a well-defined cyst radius and identical wall thickness, higher dose rates resulted for {sup 90}Y. Conclusions: To achieve the same radiological burden, the required amount of physical activity of injectable solution is lower for {sup 32}P. This is found to be a consequence of both the radionuclide physical half-life and the pattern of energy deposition frommore » the emitted radiation. According to the half-life and dose-rate results, {sup 90}Y would be a good substitute for {sup 32}P.« less

In their article entitled, “Metabolic and Structural Effects of Phosphatidylcholine and Deoxycholate Injections on Subcutaneous Fat: A Randomized, Controlled Trial,” Reeds et al analyzed the effects of phosphatidylcholine and deoxycholate (PC-DC) treatments on body composition, adipocyte function, and mechanisms responsible for fat loss. Thirteen women were enrolled; only 7 completed the study. This small sample size renders statistically significant calculations virtually impossible. The authors maintain that PC-DC injections have become increasingly popular. This may be true in Seoul, Korea, where over 6000 vials of Lipobean1 are injected monthly into human subcutaneous fat for the purpose of fat reduction. However, in many countries around the world, the practice of injection lipolysis has been banned.2 Popularity of these injections in the United States has dwindled,3 in part due to the lack of a US Food and Drug Administration (FDA)–approved agent and also due to the lack of efficacy in treating larger body regions.4 The side effects, although not morbid, are unpleasant. Noninvasive treatments such as Liposonix (Solta Medical, Inc, Bothell, Washington) and Tite FX (Invasix, Richmond Hill, Ontario, Canada)5,6 offer much more fat reduction without the cholinergic side effects that can be seen with higher-dose PC-DC injections. Despite the shortcomings of injection lipolysis as currently practiced, there has been a resurgence of interest in the topic,7 especially in Europe and Asia. There are many reasons for this, including the expansion of the practice of aesthetic medicine and the desire of practitioners who mainly perform injections to have an injectable solution for reduction of protrusions. If aesthetic practitioners can fill hollow regions, they may also want to reduce or take away volume. The ability to do this precisely with an injection would be an excellent addition to the …

Various aspects of the safety of moxidectin for goats were tested in six experiments, where two pharmaceutical forms (1% injectable solution and 0.1% oral drench) of the drug were used. In experiments I and II, the drug was administered to adult goats or to kids in the following doses: 300, 600, 900 and 2×300 μg kg −1 . In experiments III and IV, the drug was administered to goats before and during pregnancy in the dose of 300 μg kg −1 . In experiments V and VI, the drug was administered to goats concurrently with an enterotoxaemia vaccine or with a flukicide in the dose of 300 μg kg −1 . An increased ( P −1 of moxidectin 1% injectable solution and among kids which received 600 or 900 μg kg −1 of moxidectin 1% injectable solution or 900 μg kg −1 moxidectin 0.1% oral drench. The salient reactions of the animals were: indifference to the environment, drowsiness, somnolence, salivation, ataxia and refusal of kids to suck their dams; they were observed 4–8 h after administration of the drug and regressed within 36 h after it. No other statistically significant adverse reactions were observed among experimental animals; no adverse reproductive effects were recorded; no effects were observed during simultaneous administration of the enterotoxaemia vaccine or the flukicide. It is concluded that although the drug appears to be safe for use to goats of all ages and reproductive stages, care should be taken to avoid inadverted overdosing.