Effects of different light sources on the stability of cinepazide maleate in sodium chloride solution / 中国基层医药

Objective:To investigate the effects of different light sources on the stability of cinepazide maleate in sodium chloride solution, providing a theoretical basis for standardizing operation for avoiding light in clinical medication.Methods:First, a standard curve was created and methodological studies were conducted. Then, intravenous drip solutions were prepared using clinically prescribed methods. Then, the absorbance of the solution of cinepazide maleate injection under outdoor light, light emitting diode (LED) light, indoor light, artificial sunlight with a color temperature of 6 500 K (D65), and under a shading condition for 1, 2, 3, and 7 hours were brought into the standard curve to obtain the concentrations, and the change of the concentrations was studied.Results:There was no light decomposition phenomenon of cinepazide maleate injection in the shading group (control group) within 7 hours. In the other four experimental groups, there was no obvious light decomposition phenomenon of cinepazide maleate injection in the LED light group. Compared with the shading group, cinepazide maleate injection in the indoor, outdoor, and D65 groups began to exhibit a light decomposition phenomenon at 1 hour ( F = 44 840.44, P < 0.001). At 2 hours, cinepazide maleate content in the outdoor and D65 groups began to decrease significantly compared with the shading group ( F = 15 459.12, P < 0.001). At 7 hours, cinepazide maleate exhibited significantly greater light decomposition in the outdoor group [(29.84 ± 0.43) L·mol -1·cm -1] and D65 group [(21.01 ± 0.51) L·mol -1·cm -1] than the shading group [(101.65 ± 1.5) L·mol -1·cm -1] ( F = 63 106.32, P < 0.001). There was no significant difference in cinepazide maleate content between LED and shading groups ( P > 0.05). Conclusion:Cinepazide maleate injection is stable under the common LED light source and therefore it is not necessary to take lightproof operation. Cinepazide maleate injection is unstable under indoor, outdoor, and D65 light sources, and it is necessary to take lightproof operation.

Compatibility stability of cinepazide maleate injection and dopamine hydrochloride injection / 中国基层医药

Objective:To investigate the compatibility stability of cinepazide maleate injection and dopamine hydrochloride injection and explore the basis for the combined application of cinnamazide maleate injection and dopamine hydrochloride injection.Methods:A method for determining cinnamazide maleate injection and dopamine hydrochloride injection was established using an ultraviolet-visible spectrophotometer and verified from March 1, 2021 to May 20, 2021. The color and pH value of the solution prepared using the two drugs were determined within 5 hours at room temperature. The content change of the prepared solution was determined using an ultraviolet-visible spectrophotometer.Results:The linear range of the mass concentration of cinnamazide maleate was 4.03 - 32.24 mg/L and the linear range of dopamine hydrochloride was 20 -120 mg/L. At 25 ℃, the color of the prepared solution did not change within 5 hours and the pH value was in the range of 4.43 ± 0.06, indicating that the pH of the prepared solution did not change markedly. The concentrations of cinnamazide maleate and dopamine hydrochloride were (98.23 ± 1.09)% and (99.96 ± 0.41)% respectively, indicating good stability.Conclusion:The prepared solution using cinepazide maleate injection and dopamine hydrochloride injection can be used within 5 hours at 25 ℃.

Estabilidade do cloridrato de vancomicina empregado em soluções de selo antimicrobiano de cateteres intravenosos centrais / Stability of vancomycin hydrochloride employed in antimicrobial seal solutions of central intravenous catheters / Estabilidad del clorhidrato de vancomicina utilizado en soluciones de sellado antimicrobiano para catéteres intravenosos centrales

Resumo Objetivo: verificar a estabilidade do cloridrato de vancomicina em soluções de selo antimicrobiano sem e com associação de heparina sódica segundo a temperatura e tempo de associação. Método: estudo experimental delineado para análise de potencial hidrogeniônico e concentração por cromatografia líquida de alta eficiência de soluções de cloridrato de vancomicina (n=06) e cloridrato de vancomicina e heparina sódica (n=06). Submeteram-se as soluções estudadas à ausência de luz, 22°C e 37°C. Análises em triplicadas (n=192) ocorreram no momento inicial (T0), três (T3), oito (T8) e 24 horas (T24) após preparo. Os dados foram submetidos à análise de variância (p≤0,05). Resultados: a concentração do antimicrobiano a 22°C apresentou redução (T0-T8) e posterior elevação (T24); o potencial hidrogeniônico diminuiu significativamente ao longo do tempo. Em 37°C a concentração aumentou em até T3 e reduziu em T24, com redução de potencial hidrogeniônico até 24 horas. A concentração das soluções de cloridrato de vancomicina e heparina sódica apresentaram variação com redução a 22°C acompanhada de aumento de potencial hidrogeniônico. Observou-se formação de precipitado por inspeção visual da associação cloridrato de vancomicina e heparina sódica (T3). Conclusão: evidenciou-se estabilidade farmacológica do cloridrato de vancomicina (5 mg/mL) e incompatibilidade física com heparina sódica (100 UI/mL) após três horas de associação nas soluções de selo antimicrobiano estudadas.

Abstract Objective: to verify the stability of vancomycin hydrochloride in antimicrobial seal solutions with and without association of heparin sodium according to temperature and association time. Method: an experimental study designed for the analysis of hydrogenionic potential and concentration by means of high-efficiency liquid chromatography of vancomycin hydrochloride (n=06) and vancomycin hydrochloride and heparin sodium (n=06). The solutions studied were submitted to absence of light, as well as to 22°C and 37°C. Analyses in triplicate (n=192) were performed at the initial moment (T0) and three (T3), eight (T8) and 24 hours (T24) after preparation. The data were submitted to analysis of variance (p≤0.05). Results: concentration of the antimicrobial at 22°C presented a reduction (T0-T8) and a subsequent increase (T24); hydrogenionic potential decreased significantly over time. At 37°C, the concentration increased up to T3 and decreased at T24, with a reduction of hydrogenionic potential up to 24 hours. Concentration of the vancomycin hydrochloride and heparin sodium solutions varied with a reduction at 22°C, accompanied by increased hydrogenionic potential. Precipitate formation was observed by visual inspection of the vancomycin hydrochloride-heparin sodium association (T3). Conclusion: pharmacological stability of vancomycin hydrochloride (5 mg/mL) and physical incompatibility with heparin sodium (100 IU/mL) were evidenced after three hours of association in the antimicrobial seal solutions studied.

Resumen Objetivo: verificar la estabilidad del clorhidrato de vancomicina en soluciones de sellado antimicrobiano solo y combinado con heparina sódica según la temperatura y el tiempo de combinación. Método: estudio experimental diseñado para analizar el potencial de hidrógeno y la concentración por cromatografía líquida de alta resolución de soluciones de clorhidrato de vancomicina (n=06) y de clorhidrato de vancomicina y heparina sódica (n=06). Las soluciones estudiadas fueron sometidas a ausencia de luz, 22°C y 37°C. Se realizaron análisis por triplicado (n=192) en el momento inicial (T0), a las tres (T3), ocho (T8) y 24 horas (T24) después de la preparación. Los datos fueron sometidos a análisis de varianza (p≤0,05). Resultados: la concentración de antimicrobiano a 22°C mostró una reducción (T0-T8) y un posterior aumento (T24); el potencial de hidrógeno disminuyó significativamente con el tiempo. A 37°C, la concentración aumentó hasta T3 y disminuyó en T24, el potencial de hidrógeno disminuyó hasta las 24 horas. La concentración de las soluciones de clorhidrato de vancomicina y heparina sódica mostró variación con la reducción a 22°C acompañada de un aumento del potencial de hidrógeno. Mediante inspección visual se observó la formación de un precipitado al combinar clorhidrato de vancomicina y heparina sódica (T3). Conclusión: el clorhidrato de vancomicina (5 mg/ml) presentó evidencia de estabilidad farmacológica e incompatibilidad física con la heparina sódica (100 UI/ml) después de las tres horas de haberse realizado la combinación en las soluciones de sellado antimicrobiano estudiadas.

Captopril oral solution for pediatric use: formulation, stability study and palatability assessment in vivo

Abstract he aim of this work was to develop an oral solution of captopril at 5 mg/mL preservative-free. Two formulations were prepared, one containing sweetener (formulation 1) and the other without this excipient (formulation 2). The results found of validation parameters from analytical method performed by HPLC for captopril were, linearity 0.9998, the limit of detection 15.71 µg/mL, the limit of quantification 47.60 µg/mL, repeatability 1.05%, intermediate precision 2.42%, accuracy intraday 101,53%, accuracy inter-day 99.85%. Moreover, the results found for captopril disulfide were, linearity 0.9999, limit of detection 0.65 µg/mL, limit of quantification 1.96 µg/mL, repeatability 2.28%, intermediate precision 1.51%, accuracy intraday 101.36%, accuracy inter-day 100.29%. The appearance of formulations was clear and colorless, pH measures were 3.12 and 3.04, dosage of captopril and captopril disulfide were 99.45% and 99.82%, 0.24% and 0.12% for formulation 1 and formulation 2, respectively. The stability study demonstrated that the concentration of captopril and captopril disulfide in the formulations was > 90% and below 3%, respectively. The in vivo palatability study in animals and humans showed that Formulation 1 containing the sweetener had better acceptance. Thus, the sweetener was able to improve the unpleasant taste of the formulation

Forced degradation studies to identify organic impurities in pharmaceuticals: a Brazilian perspective

Objective: The aim of this study was to highlight and sediment the necessary steps to be followed while conducting forced degradation studies to identify degradation products and to describe the Brazilian and international regulations associated with degradation studies of drugs and drug products. Methods: This review was conducted based on the Brazilian guidance tools as RDC 53/2015, Guide 4 and Question and Answer resource; references used as international guides; and articles in the field of degradation product analyses. Results: Characterization of the impurity profile for a substance, and development of indicative stability methods are essential criteria for compliance with current legislation, and address a legitimate health concern. As this matter falls under the purview of recently published regulation, many doubts remain regarding methods of conducting studies of forced degradation, and development of methods indicative of stability. Analytical conditions predict degradation after exposing them to thermal, humid, acidic, basic, oxidation, photolytic, and metal ion conditions. Conclusions: Although RDC 53/2015 outlines the parameters of degradation, the analytical conditions are not specified, as well as in other international standards. A well-designed forced degradation study is key to obtaining a good stability indicating method with peak purity and mass balance.

Optimization of blending method of Shuanghuanglian injection and its stability study in different solvents / 国际中医中药杂志

Objective:To optimize the blending method of Shuanghuanglian injection, and to investigate its stability in different solvents (0.9% sodium chloride injection, 5% glucose injection, 10% glucose injection, glucose and sodium chloride injection). Methods:By using orthogonal test to optimize the best dissolution method of Shuanghuanglian injection By measuring the content change of insoluble particles, pH value and principal components (baicalin, forsythione, chlorogenic acid) in the finished products to investigatethe stability of Shuanghuanglian injection in different solvents. Results:The optimal blending method of Shuanghuanglian injection was to add 5 ml sterilized water for injection into the vial and oscillate at 1 200 r/min frequency for 5 min. The main constituents of Shuanghuanglian injection were stable in 8 h in the infusion of four kinds of finished products. Insoluble particles in 0.9% sodium chloride infusion and 5% glucose infusion met the requirements within 8 h, and insoluble particles in 10% glucose infusion and 6 h glucose and sodium chloride infusion met the requirements. The pH value of 0.9% sodium chloride infusion within 8 h met the optimal requirements of the best compatibility, 5% glucose infusion within 2 h met the requirements, and 4 h sodium chloride infusion met the requirements of the best compatibility. Conclusion:This study optimized the best preparation method of Shuanghuanglian (freeze-dried) for injection. Sodium chloride injection should be used as the solvent to prepare finished infusion in clinical application, and 5% glucose injection should be prepared just before use.

A Case for Expanding Thermochromic Vial Monitor Technology to Insulin and Other Biologics

Insulin quality and efficacy determine glycemic control, which determines quality of life for people with diabetes. Insulin efficacy is reducedby heat exposure, especially in tropical climates, remote areas, and with improper handling. Insulin doses can be adjusted based on bloodglucose monitoring, which may compensate for lack of viability. However, a measured response may be difficult with otherbiopharmaceuticals. Thermochromic vial monitor technology developed for oral polio vaccines (vaccine vial monitors) is an inexpensive,easily available, visible modality which can be used for insulin and other biopharmaceuticals to detect excessive heat exposure and thusreduced potency at any point in the cold-chain, till the end-users, thus improving patient care. Regulatory authorities must urgently considerthe need to impose mandatory use of this technology for all biopharmaceuticals, including insulin, to ensure efficacy till end usage.

Study on prescription process of nanoemulsion of Perilla frutescens essential oil and preliminary quality evaluation / 中草药

Objective: Using Perilla frutescens as a model drug, the nanoemulsion of Perilla frutescens essential oil (PFEO) were prepared, and the formulation process research and preliminary quality evaluation were carried out. Methods: The cosurfactants were determined according to the amount of PFEO dissolved in various excipients. The HLB value method was used to preliminarily screen surfactants suitable for oil-in-water (O/W) nanoemulsions, and the surfactants with dosage safety were further screened to determine the composition of nanoemulsion formulations. By drawing a pseudo-ternary phase diagram, the nanoemulsion region size, drug loading, water content, and conductivity, viscosity, particle size, distribution, and stability was comprehensively compared to optimize the prescription. This study investigated the appearance, physicochemical properties (viscosity, pH value, conductivity, electrical conductivity, particle size, Zeta potential), stability, in vitro permeability properties and nasal mucosa irritation of the nanoemulsion of PFEO. Results: The final optimized nanoemulsion formulation was 14.3% PFEO-9.5% Transcutol P-19.1% Labrasol-57.1% water. The nanoemulsion of PFEO prepared according to the optimized prescription was uniform, transparent, clear, with good fluidity. The viscosity was (3.68 ± 0.17) mPa∙s, pH value was (6.18 ± 0.03), the electrical conductivity was (109.61 ± 0.89) μS/cm, the Zeta potential was (-7.08 ± 1.82) mV, and the particle size was (49.98 ± 1.55) nm. The results of transmission electron microscope experiment showed that, the droplets of PFEO nanoemulsion were spherical with the particle size within 100 nm. The stability test results showed that the nanoemulsion of PFEO had centrifugal stability, dilution stability, long-term stability and temperature stability. After storage at room temperature and unsealed for one month and six months, the percentage change of the average perillaldehyde content of PFEO nanoemulsion and PFEO was 1.8% and 17.48%, respectively. The nasal mucosal irritation test results showed that the PFEO nanoemulsion administration group had no significant difference from the blank saline group. Conclusion: The appearance and related physical and chemical properties of PFEO nanoemulsion prepared by optimized prescription process meet the quality requirements of nanoemulsion, with drug stability, drug permeability and safety.

Study on the inclusion technic of hydroxypropyl-β-cyclodextrin in tea tree oil and evaluation of its included compounds / 国际中医中药杂志

Objective@#This study takes hydroxypropyl-β-cyclodextrin (HP-β-CD) as the inclusion materials to optimize the preparation technic of tea tree oil (TTO) and evaluate its pharmaceutical performance.@*Methods@#Take the production rate of HP-β-CD tea tree oil inclusion and entrapment rate as the evaluation index, taking the orthogonal test method to optimize the production technic of tea tree oil (HP-β-CD inclusion and using infrared (IR), differential thermal scanning (DSC) method to characterize the inclusion compound to analyze the stability of TTO-HP-β-CD.@*Results@#The best technic to produce HP-β-CD tea tree oil is as follow: the ratio of TTO and HP-β-CD should be equal to 1/10, at 40 ℃, within 1 h. The average drug loading shoud be 9.25% ± 3.25%. The IR, DSC characterization results showed that the characteristic peak of tea tree oil disappeared after the microspheres, which indicated the HP-β-CD encapsulated the tea tree oil with good compatibility. In 80 ℃ water bath, the TTO-HP-β-CD was stable with the retention rate 40% after 8 h, the retention rate was 4.32 times than that of the unwrapped tea tree oil.@*Conclusions@#The HP-β-CD tea tree oil obviously has higher rate of inclusion and stability. Therefore, it’s worth to promoting and being used in the pharmacy preparations and cosmetics field.

Storage and disposal of expired medicines in home pharmacies: emerging public health problems / Armazenamento e descarte dos medicamentos vencidos em farmácias caseiras: problemas emergentes para a saúde pública

ABSTRACT Objective To characterize storage and disposal practices associated with expired medicines in home pharmacies of Primary Care users. Methods Cross-sectional study based on data collected from 423 users of 15 Primary Care units located in a Brazilian city, between August 2014 and July 2016. Data were collected via face-to-face interviews. Categorical (demographic and socioeconomic characteristics) and continuous variables were expressed as proportions and means and standard deviations, respectively . Storage behaviors and disposal practices associated with unused and expired medicines were described as frequencies. Results Most (83%) interviewees were female and approximately 70% had completed high school. The kitchen was the most common medicine storage place (58.6%). Approximately 75% of participants reported inappropriate medicine disposal practices. Conclusion This study revealed high rates of inappropriate medicine disposal practices with direct impacts on pharmacological treatment and the environment. Continuing education of healthcare professionals and the general public is required to raise awareness about proper medicine use and disposal.

RESUMO Objetivo Caracterizar o armazenamento e o descarte de medicamentos vencidos contidos em farmácias caseiras de usuários da Atenção Primária à Saúde. Métodos Estudo transversal, realizado com 423 usuários de 15 unidades de saúde da Atenção Primária em um município brasileiro. Os dados foram coletados de agosto de 2014 a julho de 2016, por meio de entrevistas face a face. As características demográficas e socioeconômicas foram descritas por meio de proporções para as variáveis categóricas. As formas de armazenamento e o descarte de medicamentos vencidos ou não vencidos foram descritos em forma de frequência. Resultados Dentre os entrevistados, 83% eram do sexo feminino e aproximadamente 70% possuíam Ensino Médio completo. A cozinha foi o local mais citado para armazenamento de medicamentos (58,6%). Cerca de 75% dos participantes relataram descartar os medicamentos de forma incorreta. Conclusão O estudo evidenciou que grande proporção dos entrevistados possui hábitos incorretos de descarte, que, por sua vez, impactam diretamente no tratamento medicamentoso e na natureza. Assim, é necessária a educação continuada dos profissionais de saúde e da população, a fim de conscientizar a população sobre a correta utilização e o descarte de medicamentos.

Development of stability-indicating LC method assisted by Design of Experiment for fenticonazole cream analysis in presence of degradation product

Fenticonazole is an antifungal drug widely used in a cream formulation including as a generic medicine. Stability studies of fenticonazole in a cream formulation are very scarce. In this research, we intent to contribute to generic medicines quality control and provide reliable data seeking for insertion of fenticonazole monograph in official compendia. Therefore, in this work it was studied the behavior of fenticonazole under several conditions and developed a stability-indicating LC method to separate the degradation products and quantify the drug in presence of them, using the Design of Experiments (DoE) as tool to achieve robust and easy transferable method. Fenticonazole stability was evaluated under aqueous, alkaline (0.1 M NaOH), acidic (0.1 M HCL) and oxidative (3% v/v, H2O2) at ambient temperature and heating at 90°C, over 6 hours. The drug shows to be unstable under all stressed test conditions. It was completely degraded under acid medium with arising of degradation products. The robust and stability indicating LC method was validated. It is able to reveal the fenticonazole instability and to separate its degradation product with accuracy and precision (CV ˂ 2%) and without any placebo interferences.(AU)

Preformulation of a liquid dosage formulation of captopril for pediatric use: drug-excipient compatibility and stability studies

Currently, medications used in children are typically modified from pharmaceutical dosage forms designed for adults. Captopril is widely adapted to liquid formulations for use in hospitals. Its stability in the aqueous medium is reduced since it undergoes oxidation producing captopril disulfide (its main metabolite). The aim of this formulation study was to suggest favorable conditions for the development of a stable captopril formulation. The compatibility between the drug and excipients was evaluated by differential scanning calorimetry analysis (DSC). For studies in solution, different formulations were prepared according to a factorial design varying EDTA concentration, water purity and pH. The resultant formulations were stored at 60°C and analyzed over a twelve-day period using HPLC. The DSC curves obtained suggested, although not conclusive to elucidation, interactions of captopril with citric acid and sucralose. The stability study of these solutions revealed that the variables significantly influenced captopril content, which degraded at zero order kinetics and rates differing by a factor of up to 7 times, where pH proved the most influential factor. Interactions between variables were observed. Therefore, development of a stable captopril formulation is feasible provided EDTA and a buffering agent is used at suitable concentrations (0.08% and pH 3.85).

Content characteristics and cytotoxicity detection of silver ion products / 中华烧伤杂志

Objective@#To analyze the silver content, homogeneity, and cytotoxicity of silver-containing products.@*Methods@#(1) Five kinds of silver-containing products A, B, C, D, and E were purchased from the market, and products A, B, C, and D are liquid or gel form while product E was dressing form. The silver content of each product and the homogeneity of product E were determined by flame method. The sample number was 3. (2) Human hepatocellular carcinoma cell line (HepG2) was selected as the evaluation model. Four silver-containing products A, B, C, and D were diluted with high-glucose dulbecco′s modified eagle medium (DMEM) at multiple ratios of 1∶100, 1∶200, 1∶400, and 1∶800, and then they were used for cell culture. Cells cultured with high-glucose DMEM and high-glucose DMEM containing 20 μg/mL silver nitrate were used as blank control and positive control, respectively. The cell viability was determined by methyl thiazolyl tetrazolium assay, and each sample number was 5. (3) Four mass concentrations of 0.031 3, 0.062 5, 0.125 0, and 0.250 0 μg/mL were prepared from silver-containing product A, and then they were used to culture HepG2 cell. Cells cultured with high-glucose DMEM containing fetal calf serum and 294 μg/mL potassium dichromate were used as positive control, while those containing fetal calf serum were used as blank control. Hoechst 33258 staining method was used to detect apoptosis rate of cells. The tail moment, tail length, and the percentage of DNA in the tail of cells were observed by comet assay to evaluate DNA damage. The sample numbers were all 3. Data were processed with one-way analysis of variance and least significant difference-t test.@*Results@#The silver content of products A, B, C, and D was (256.5±1.5) μg/mL, (271.5±1.3) μg/mL, (652.4±2.6) μg/g , (330.0±2.1) μg/g, which was in accordance with labelled amount. The silver content of product E was (0.158±0.013) mg/g, and the silver content of each piece of product E was (0.125±0.017) mg/g, showing good uniformity of product E. (2) Compared with the rate of blank control, the cell survival rates of product A at the dilution ratio of 1∶100, product B at the dilution ratio of 1∶100, and product C at the dilution ratio of 1∶100 and 1∶200 were significantly reduced (t=35.506, 8.914, 37.594, 30.693, P<0.01). Compared with the rate of positive control, the cell survival rates of product A at the dilution ratio of 1∶200, 1∶400, and 1∶800, product C at the dilution ratio of 1∶400 and 1∶800, products B and D at each dilution ratio were increased significantly (t=27.537, 18.262, 18.709, 26.333, 41.762, 15.776, 19.759, 20.443, 15.715, 26.792, 24.963, 31.803, 30.537, P<0.01). (3) The apoptosis rates of cells treated by 0.250 0 μg/mL product A and positive control were (6.1±0.4)% and (62.2±3.9)% respectively, which were significantly higher than the apoptosis rate of blank control [(3.3±0.7)%, t=13.327, 30.475, P<0.05]. The apoptosis rates of cells treated by 0.031 3, 0.062 5, 0.125 0 μg/mL product A were (2.9±0.4)%, (3.1±0.4)%, and (4.2±0.9)% respectively, which were close to the apoptosis rate of blank control (t=1.181, 0.133, 1.097, P>0.05). (4) The tail moment, tail length, and tail DNA percentage of cells cultured with 0.125 0 and 0.250 0 μg/mL product A were significantly higher than those cultured with blank control (t=29.026, 51.194, 21.851, 36.138, 24.721, 50.455, P<0.05 or P<0.01). However, the tail moment, tail length, and tail DNA percentage of cells cultured with 0.031 3 and 0.062 5 μg/mL product A were close to those cultured with blank control (t=5.878, 3.429, 2.779, 1.960, 1.328, 7.763, P>0.05).@*Conclusions@#The silver content of silver-containing products meets the requirements of the labeling. The concentration of product C is higher than that of other products, leading to a greater possibility of decreasing the survival rate of HepG2 cells. It is suggested that the products A and B should be taken as reference in the concentration setting of silver ion products. The product solution with higher concentration may have higher risk of damage to cell DNA. Therefore, it is not recommended to upregulate silver content of relevant products blindly in order to achieve better antibacterial effect.

Synthesis, stability and activity of the prodrugs of dihydroorotate dehydrogenase inhibitors / 药学学报

This study was conducted to improve structural instability of a highly active DHODH inhibitor A found in our group. Twelve prodrugs were synthesized by modifying the carboxyl group. The enzyme activity test of 12 prodrugs A1−A12 demonstrated that A1−A5 displayed weak inhibitory activity, and A6−A12 displayed no activity, which met the action mechanism of designed prodrug. The structural stability of A1−A12 in methanol and pH 2.0, 9.0 buffers were tested, and the results showed that A12 could avoid intramolecular ring-formation in CH3OH, A1−A8 were easily hydrolyzed under acidic conditions, and A9−A12 were inclined to hydrolyze under alkaline conditions. The cell proliferation inhibitory activity of 12 prodrugs were evaluated, in which compound A12 displayed excellent activity (IC50=0.63 μmol·L−1) similar to brequinar. These results laid a good foundation for conducting further vivo studies.

Quality of bevacizumab (Avastin®) repacked in single-use glass vials for intravitreal administration / Avaliação da qualidade do bevacizumabe (Avastin®) fracionado em frascos de vidro de dose única para administração intravítrea

ABSTRACT Purpose: Avastin® (bevacizumab) is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody given as an off-label drug by intravitreal administration for treatment of ocular diseases. The drug's clinical application and its cost-benefit profile has generated demand for its division into single-use vials to meet the low volume and low-cost doses necessary for intraocular administration. However, the safety of compounding the drug in single-use vials is still under discussion. In this study, the stability and efficacy of Avastin® repacked in individual single-use glass vials and glass ampoules by external compounding pharmacies were evaluated. Methods: Polyacrylamide gel electrophoresis (PAGE), size-exclusion chromatography (SEC), dynamic light scattering (DLS), and turbidimetry were selected to detect the formation of aggregates of various sizes. Changes in bevacizumab biological efficacy were investigated by using an enzyme-linked immunosorbent assay (ELISA). Results: Repacked and reference bevacizumab showed similar results when analyzed by PAGE. By SEC, a slight increase in high molecular weight aggregates and a reduction in bevacizumab monomers were observed in the products of the three compounding pharmacies relative to those in the reference bevacizumab. A comparison of repacked and reference SEC chromatograms showed that the mean monomer loss was ≤1% for all compounding pharmacies. Protein aggregates in the nanometer- and micrometer-size ranges were not detected by DLS and turbidimetry. In the efficacy assay, the biological function of repacked bevacizumab was preserved, with <3% loss of VEGF binding capacity relative to that of the reference. Conclusion: The results showed that bevacizumab remained stable after compounding in ampoules and single-use glass vials; no significant aggregation, fragmentation, or loss of biological activity was observed.

RESUMO Objetivos: Avastin® (bevacizumabe) é um anticorpo monoclonal inibidor do fator de crescimento endotelial de vasos (VEGF) utilizado "off-label" por meio de administração intravítrea para o tratamento de doenças oculares. A sua aplicação clínica associada ao custo-benefício do medicamento gerou uma demanda para seu fracionamento em frascos de dose única para utilização pela via intraocular. No entanto, a segurança do fracionamento do anticorpo em frascos de dose única ainda é alvo de discussão. Neste trabalho, a estabilidade e a eficácia do Avastin® fracionado em frascos ou ampolas de vidro de dose unitária por farmácias de manipulação do mercado foram avaliadas. Métodos: As técnicas de eletroforese em gel de poliacrilamida (PAGE), cromatografia por exclusão de tamanho (SEC), espalhamento dinâmico da luz (DLS) e turbidimetria foram empregadas para avaliar a formação de agregados de diferentes tamanhos. Alterações na atividade biológica do bevacizumabe foram estudadas utilizando ELISA. Resultados: Amostras referência e do bevacizumabe fracionado apresentaram resultados semelhantes quando analisado por gel de poliacrilamida. Por cromatografia por exclusão de tamanho, um pequeno aumento na quantidade de agregados de alta massa molar seguido de uma redução nos monômeros do bevacizumabe foram observados para as amostras das três farmácias de manipulação quando comparado ao referência. A comparação dos cromatogramas mostrou uma quantidade de redução do monômero inferior a 1% para todas as amostras fracionadas. Por espalhamento dinâmico da luz e turbidimetria, não foram detectados agregados de proteína na faixa de tamanho de micrômetro e nanômetro. No ensaio de eficácia, o bevacizumabe fracionado preservou sua função biológica pois apresentou menos de 3% de perda na capacidade de ligação ao VEGF quando comparado ao referência. Conclusão: Este estudo sugere que o bevacizumabe se mantem estável após fracionamento em ampolas e frascos de vidro de dose unitária pois não foram observadas agregação e/ou fragmentação de proteínas e perda de atividade biológica em quan tidades significativas.

Stability of the new type of L. Bulgaricus microcapsule / 药学学报

A new type of L. Bulgaricus microcapsule was prepared to improve stability and resistance of L.Bulgaricus probiotics in harsh environments. An optimal method of preparation of L. Bulgaricus microcapsule is as follow. L. Bulgaricus was mixed with 3% alginate solution. The concentration of bacterial suspension was 1×109 cfu·mL-1. The mixture was microencapsulated by extrusion into 2% CaCl2 solution with a dispensing equipment. After 30 min solidification, the gel beads were lyophilized to obtain L.Bulgaricus microcapsules. The microencapsulation technology was aimed to improve the stability and survival rate of L. Bulgaricus. The microcapsule was spherical with uniform particle size and intact structure. The tolerance of acid, high temperature, high humidity and the long-term stability of freeze-dried powder and microcapsule were evaluated. The results indicated that microencapsulation technic could greatly improve stability and resistance of L. Bulgaricus probiotics in harsh environments.

Compatibility: drugs and parenteral nutrition / Compatibilidade: medicamentos e nutrição parenteral

ABSTRACT Objective Standardization and systematization of data to provide quick access to compatibility of leading injectable drugs used in hospitals for parenteral nutrition. Methods We selected 55 injectable drugs analyzed individually with two types of parenteral nutrition: 2-in-1 and 3-in-1. The following variables were considered: active ingredient, compatibility of drugs with the parenteral nutrition with or without lipids, and maximum drug concentration after dilution for the drugs compatible with parenteral nutrition. Drugs were classified as compatible, incompatible and untested. Results After analysis, relevant information to the product’s compatibility with parental nutrition was summarized in a table. Conclusion Systematization of compatibility data provided quick and easy access, and enabled standardizing pharmacists work.

RESUMO Objetivo Padronizar e sistematizar informações, proporcionando um acesso rápido à compatibilidade dos principais medicamentos injetáveis utilizados no âmbito hospitalar para a nutrição parenteral. Métodos Foram selecionados 55 medicamentos injetáveis, os quais foram analisados individualmente com dois tipos de nutrição parenteral: dois em um, e três em um. Foram consideradas as seguintes variáveis: princípio ativo, compatibilidade dos medicamentos com a nutrição parenteral com e sem lipídios, e respectiva concentração máxima do medicamento após diluição, para os medicamentos compatíveis com a nutrição parenteral. Os fármacos foram classificados como compatível, incompatíveis e não testado. Resultados Após a análise, as informações pertinentes à compatibilidade do medicamento com a nutrição parenteral foram sintetizadas uma tabela. Conclusão A sistematização das informações de compatibilidade proporcionou um acesso rápido e fácil, viabilizando e padronizando o trabalho do farmacêutico.

Investigation of formulation, preparation and stability of rosuvastatin calcium tablets / 第二军医大学学报

Objective To explore the formulation and preparation technique of rosuvastatin calcium tablets with satisfactory stability and reproducibility. Methods Using suitable formulations, we prepared the rosuvastatin calcium granulates by high shear mixer and fluid bed separately, and compared their influences on the granulate properties, tablet characteristics and dissolution. The reproducibility of formulation and preparation technique was investigated. Furthermore, the factors affecting the formulation were also investigated. Results Compared with the fluid bed, granulation using high sheer mixer was more suitable for preparing rosuvastatin calcium granulates. The selected formulation and preparation technique yielded 3 batches of rosuvastatin calcium tablets which met the quality requirement. The tablets had a comparable dissolution profiles to "Crestor " of AstraZeneca. The stability of rosuvastatin calcium was largely affected by the strong light, high humidity and high temperature. Conclusion The optimized formulation and preparation technique have good reproducibility for preparing rosuvastatin calcium tablets, which have good stability.

The stability study of vitamin c tablets made by automatic dispensing machine in working mode / 中国药学杂志

OBJECTIVE: To observe the stability status of vitamin C tablets which are made by the dispensing machine in working mode and try to find out the procedures which may bring some potential hazards in the new modes. METHODS: According to the Pharmacopoeia the procedures were detected and collected data of the Vitamin C Tablets were made by dispensing machine in existing working mode. The data is collected from different aspects, including the color of drug solution, pharmic content, microbial limit from the storage and dispensing process. Then we compare these data with the factory's report and analyse the differences. RESULTS: There is no significant difference between the data we get and the factory's report of vitamin C tablets made by the dispensing machine in working mode, including the color of drug solution, pharmic content and the appearance of tablets. But there is an increasing trend of bacterial colonies in microbial limit tests for the two samples. CONCLUSION: The status of vitamin C tablets made by dispensing machine in working mode is generally stable. The increasing number of bacterial colonies shows that the time when drugs are exposed in the air, the cleanliness of dispensing environment and pharmaceutical package material are the key for drug quality control.

Organizadores e cortadores de comprimidos: riscos e restrições ao uso / Pill organizers and pill cutters: risks and limitations / Organizadores y cortadores de comprimidos: riesgos y restricciones del uso

Com base em análise documental, foram discutidas e problematizadas as limitações associadas à utilização de organizadores e cortadores de comprimidos, como questão de saúde pública. Os organizadores destinados ao armazenamento e transporte de comprimidos e cápsulas expõem essas formas farmacêuticas a fatores ambientais dos quais estariam protegidos em suas embalagens originais, comprometendo sua estabilidade, eficácia e segurança. Os cortadores oferecem risco adicional quanto a perda da eficácia, reações adversas e intoxicação. Por outro lado, o transporte de medicamentos pelo usuário é reflexo da conciliação entre autonomia e autocuidado e a partição de comprimidos é necessária para cumprir certos regimes posológicos. Conclui-se que cabe aos profissionais observar e orientar pacientes e cuidadores, visando à adequação dessas condutas e à prevenção dos riscos envolvidos.

In this essay, based on documental analysis, the limitations associated with the use of pill organizers and cutters are discussed and analyzed as a matter of public health. The use of the organizers for storing and carrying tablets and capsules exposes these medications to environmental factors from which their original packaging protected them, compromising their stability and safeness. Cutters also pose the additional risk of causing loss of efficacy, adverse reactions and overdose. On the other hand, the user carrying their own medication reflects the balance between autonomy and self-care, and splitting is sometimes required to comply with certain regimens. It can be concluded that healthcare professionals should observe and guide patients and caregivers in order to avoid risks.

Objetivo Con base en análisis documental, se discutieron y señalaron los problemas de las limitaciones asociadas a la utilización de organizadores y cortadores de comprimidos, con respecto a la salud pública. Los organizadores destinados al almacenamiento y transporte de comprimidos y cápsulas exponen las formas farmacéuticas a factores ambientales de los cuales estarían protegidos en sus embalajes originales, comprometiendo su estabilidad, eficacia y seguridad. Los cortadores ofrecen riesgo adicional con relación a la pérdida de la eficacia, reacciones adversas e intoxicación. Por otro lado, el transporte de medicamentos por el usuario es reflejo de la conciliación entre autonomía y autocuidado, y la partición de comprimidos es necesaria para cumplir ciertos regímenes posológicos. Se concluye que resta a los profesionales observar y orientar pacientes y cuidadores, buscando la adecuación de esas conductas y la prevención de los riesgos involucrados.