Measurement, analysis and prediction of amoxicillin oral dose stability from integrated molecular description approach and accelerated predictive stability (APS)

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Camille Merienne ◽  
Chloe Marchand ◽  
Samira Filali ◽  
Damien Salmon ◽  
Christine Pivot ◽  
...  

AbstractBackgroundStability of low amoxicillin oral dosage form (5 mg) used in reintroduction drug test was not fully documented. Furthermore, the impact of (1) salt moiety of amoxicillin and (2) amoxicillin – excipient interactions upon the antibiotic formulation stability during the storage was not characterized so that the estimation of the pharmaceutical expiration date from shelf-life was uncertain. Thus, the main goal of this study was to estimate the shelf-life of two formulations of amoxicillin, using a semi-predictive methodology.MethodsAmoxicillin sodium (AS) and amoxicillin trihydrate (ATH), corresponding to 5-mg amoxicillin, were compounded with microcrystalline cellulose (MCC) in oral hard capsules which were, then, submitted to four environmental conditions (25 °C / 60% or 80% relative humidity (RH); 40 °C / 75% RH; 60 °C / 5% RH) in climatic chambers for 45 and 84 days. Therefore, the characterization of amoxicillin-MCC mixture was assessed by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) The profiles of amoxicillin content (determined by stability indicating chromatographic method) as a function of storage time, temperature and RH were fitted to pre-defined kinetic models performed by accelerated predictive stability (APS).ResultsATR-FTIR analysis of AS, ATH, MCC and bulk specimens stored in heated and humid atmosphere confirmed water sorption to cellulose described by a broad and unresolved 3600 to 3000 cm−1 band associated with (1) general intramolecular and intermolecular hydrogen bonding between water and hydroxyl groups of the cellulose, and with (2) free hydroxyl in cellulose. Moreover, a dramatic decrease of absorption at 1776 and 1687 cm−1 respectively characteristic of the β-lactam ring (νC=O) and amide group (νC=O), was revealed as a consequence of AS and ATH degradation caused by moisturization of bulk. Amoxicillin degradation was established by chromatographic analysis showing faster AS degradation than ATH throughout time exposure. The combined effects of temperature – RH were successfully modeled by APS, where AS and ATH showed accelerated (auto-catalysis degradation mechanism) and linear degradation, respectively. The faster AS degradation was assumed to be linked to lower hydrogen donor to hydrogen acceptor count ratio and polar surface than ATH, increasing the probability of AS hydrolysis by water adsorption to AS-MCC solid dispersion (e.g., by reduction of protective intramolecular hydrogen bonds between AS molecules). Furthermore, the compounding which involved a drastic homogenization of solids may have affected the crystalline degree of MCC with an increase of amorphous phase more sensitive to water adsorption.ConclusionsThe improvement of amoxicillin compounding for oral dose forms might be rationalized by taking into account the molecular descriptors of salt moiety and excipients, improved by the choice of an appropriate process of production, characterized from infrared vibrational spectroscopy and chromatographic analysis and finally predicted from accelerated stability assays.

Polymers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 716
Author(s):  
Milad Yaghoubi ◽  
Ali Ayaseh ◽  
Kazem Alirezalu ◽  
Zabihollah Nemati ◽  
Mirian Pateiro ◽  
...  

The present study was conducted to assess the impact of chitosan coating (1%) containing Artemisia fragrans essential oil (500, 1000, and 1500 ppm) as antioxidant and antimicrobial agent on the quality properties and shelf life of chicken fillets during refrigerated storage. After packaging meat samples, physicochemical, microbiological, and organoleptic attributes were evaluated at 0, 3, 6, 9, and 12 days at 4 °C. The results revealed that applied chitosan (CH) coating in combination with Artemisia fragrans essential oils (AFEOs) had no significant (p < 0.05) effects on proximate composition among treatments. The results showed that the incorporation of AFEOs into CH coating significantly reduced (p < 0.05) pH, thiobarbituric acid reactive substances (TBARS), and total volatile base nitrogen (TVB-N), especially for 1% CH coating + 1500 ppm AFEOs, with values at the end of storage of 5.58, 1.61, and 2.53, respectively. The coated samples also displayed higher phenolic compounds than those obtained by uncoated samples. Coated chicken meat had, significantly (p < 0.05), the highest inhibitory effects against microbial growth. The counts of TVC (total viable counts), coliforms, molds, and yeasts were significantly lower (p < 0.05) in 1% CH coating + 1500 ppm AFEOs fillets (5.32, 3.87, and 4.27 Log CFU/g, respectively) at day 12. Organoleptic attributes of coated samples also showed the highest overall acceptability scores than uncoated ones. Therefore, the incorporation of AFEOs into CH coating could be effectively used for improving stability and shelf life of chicken fillets during refrigerated storage.


MRS Bulletin ◽  
2010 ◽  
Vol 35 (1) ◽  
pp. 41-47 ◽  
Author(s):  
E. Grossman ◽  
I. Gouzman ◽  
R. Verker

AbstractIn the last 40 years, the increased space activity created a new form of space environment of hypervelocity objects—space debris—that have no functional use. The space debris, together with naturally occurring ultrahigh velocity meteoroids, presents a significant hazard to spacecraft. Collision with space debris or meteoroids might result in disfunction of external units such as solar cells, affecting materials properties, contaminating optical devices, or destroying satellites. The collision normally results in the formation of additional debris, increasing the hazard for future missions. The hypervelocity debris effect is studied by retrieving materials from space or by using ground simulation facilities. Simulation facilities, which include the light gas gun and Laser Driven Flyer methods, are used for studying the materials degradation due to debris impact. The impact effect could be accelerated when occurring simultaneously with other space environment components, such as atomic oxygen, ultraviolet, or x-ray radiation. Understanding the degradation mechanism might help in developing materials that will withstand the increasing hazard from the space debris, allowing for longer space missions. The large increase in space debris population and the associated risk to space activity requires significant measures to mitigate this hazard. Most current efforts are being devoted to prevention of collisions by keeping track of the larger debris and avoiding formation of new debris.


2021 ◽  
pp. 85-94
Author(s):  
Ja.A. Vakhrusheva ◽  
◽  
D.N. Smirnov ◽  
I.S. Makushchenko ◽  
◽  
...  

The work carried out studies of the physicomechanical properties of polysulfide sealants of brands of U-30M and UT-31 after thermal, light aging, and the assessment of mushrooms. The data on the resistance of sealants of brands U-30M and UT-31 are investigated and summarized after the impact of accelerated climatic tests and aggressive environments. The optimal time and conditions for the storage of vulcanized sealants in the unattended state and components of sealants in warehouse conditions are determined, as well as the causes of different storage of sealing pastes based on liquid thiocola.


2016 ◽  
Vol 5 (2) ◽  
Author(s):  
Luca Fasolato ◽  
Barbara Cardazzo ◽  
Stefania Balzan ◽  
Lisa Carraro ◽  
Nadia Andrea Andreani ◽  
...  

Phenols are plant metabolites characterised by several interesting bioactive properties such as antioxidant and bactericidal activities. In this study the application of a phenols concentrate (PC) from olive vegetation water to two different fresh products – gilt-head seabream (<em>Sparus aurata</em>) and chicken breast – was described. Products were treated in a bath of PC (22 g/L; chicken breast) or sprayed with two different solutions (L1:0.75 and L2:1.5 mg/mL; seabream) and then stored under refrigeration conditions. The shelf life was monitored through microbiological analyses – quality index method for seabream and a specific sensory index for raw breast. The secondary products of lipid-peroxidation of the chicken breast were determined using the thiobarbituric acid reactive substances (TBARs) test on cooked samples. Multivariate statistical techniques were adopted to investigate the impact of phenols and microbiological data were fitted by DMfit software. In seabream, the levels of PC did not highlight any significant difference on microbiological and sensory features. DMfit models suggested an effect only on H<sub>2</sub>S producing bacteria with an increased lag phase compared to the control samples (C: 87 h <em>vs</em> L2: 136 h). The results on chicken breast showed that the PC bath clearly modified the growth of <em>Pseudomonas</em> and <em>Enterobacteriaceae</em>. The phenol dipping was effective in limiting lipid-peroxidation (TBARs) after cooking. Treated samples disclosed an increase of shelf life of 2 days. These could be considered as preliminary findings suggesting the use of this concentrate as preservative in some fresh products.


2020 ◽  
Vol 3 (3) ◽  
pp. 62-65
Author(s):  
Obhioze Augustine Akpoka

It is well established that storing hatching eggs over a longer period of time affects its quality. The current study evaluated the impact of egg storage duration in-relation to two different temperature conditions (room and refrigerator) to determine the bacterial load and shelf life of viable eggs. One hundred and twenty eggs were used for this study, 60 were boiled and 60 were raw. Thirty of the boiled eggs were stored at room temperature and the other 30 eggs were kept in the refrigerator. Similarly, 30 raw eggs were each stored at room and optimal refrigeration temperatures for eggs (< 7 oC) respectively, while the egg weight, viability and sensory tests were performed daily on the eggs. However, the eggs kept in the refrigerator were viable for longer and relatively maintained higher physical appearance and sensory quality compared to eggs kept at room temperature. In the investigation of bacterial load, the total viable count ranged from 6.0× 103 to 11.9 × 103 coliform forming unit per millilitre (cfu/ml) and 1.0 × 103 to 6.5 × 103 cfu/ml for the boiled eggs kept at room and refrigeration temperatures (BRT and BFT) respectively. More so, the bacterial counts in raw eggs obtained at room and refrigerator storage ranged from 4.8 × 103 to 6.5 × 103 cfu/ml. Subsequently, the characterization and identification of bacterial isolates indicated the presence of Salmonella pullorum, Proteus mirabilis and Pseudomonas sp. The Salmonella pullorum was isolated from all the egg samples (BRT, BFT, RRT and RFT). The Proteus mirabilis was isolated from boiled eggs kept in both room and refrigerator temperatures (BRT and BFT) while Pseudomonas sp. was obtained only from raw eggs stored in the refrigerator (RFT). In addition, the boiled eggs at room temperature started deterioration on Day 9, while its counterpart in the refrigerator began spoilage or decrease in quality from Day 16. The weight of the viable eggs in relation to the non-viable ones was statistically significant (P < 0.05). The refrigeration of eggs increases its longevity while proper hygiene and adequate boiling of eggs reduces the risk of acquiring infections through bacterial contamination.


2019 ◽  
Vol 61 (4) ◽  
pp. 645
Author(s):  
В.Б. Балакирева ◽  
В.П. Горелов ◽  
Л.А. Дунюшкина ◽  
А.В. Кузьмин

AbstractThe total, bulk, and grain boundary conductivities of proton-conducting zirconates of general formula AZr_0.95Sc_0.05O_3 – α (AZS), where A = Ca, Sr, Ba, are measured in air with different humidity levels. The conductivity is measured using the four-probe dc method (600–900°C) and impedance spectroscopy (30–800°C). The impact of humid atmosphere on the total, bulk, and grain boundary conductivities of the AZS system is studied at different humidity levels: $${{p}_{{{{{\text{H}}}_{{\text{2}}}}{\text{O}}}}}$$ = 0.04, 0.61, and 2.5 kPa. Humidity is found to have a considerable effect on the conductivity of our CaZS and BaZS at lower temperatures, suggesting the likelihood of hydronium ion-mediated transport.


Author(s):  
Alexandra E. Peters ◽  
Shandelle J. Caban ◽  
Eileen A. McLaughlin ◽  
Shaun D. Roman ◽  
Elizabeth G. Bromfield ◽  
...  

Accompanying the precipitous age-related decline in human female fertility is an increase in the proportion of poor-quality oocytes within the ovary. The macroautophagy pathway, an essential protein degradation mechanism responsible for maintaining cell health, has not yet been thoroughly investigated in this phenomenon. The aim of this study was to characterize the macroautophagy pathway in an established mouse model of oocyte aging using in-depth image analysis-based methods and to determine mechanisms that account for the observed changes. Three autophagy pathway markers were selected for assessment of gene and protein expression in this model: Beclin 1; an initiator of autophagosome formation, Microtubule-associated protein 1 light chain 3B; a constituent of the autophagosome membrane, and lysosomal-associated membrane protein 1; a constituent of the lysosome membrane. Through quantitative image analysis of immunolabeled oocytes, this study revealed impairment of the macroautophagy pathway in the aged oocyte with an attenuation of both autophagosome and lysosome number. Additionally, an accumulation of amphisomes greater than 10 μm2 in area were observed in aging oocytes, and this accumulation was mimicked in oocytes treated with lysosomal inhibitor chloroquine. Overall, these findings implicate lysosomal dysfunction as a prominent mechanism by which these age-related changes may occur and highlight the importance of macroautophagy in maintaining mouse pre-ovulatory oocyte quality. This provides a basis for further investigation of dysfunctional autophagy in poor oocyte quality and for the development of therapeutic or preventative strategies to aid in the maintenance of pre-ovulatory oocyte health.


2021 ◽  
Vol 233 ◽  
pp. 01042
Author(s):  
Lei Chao ◽  
Feilong Chen ◽  
Yi Han ◽  
Yafeng Li

Lower consumption, higher efficiency, environmental protection, and reliability are the development trends for the treatment of antibiotic wastewater in future. To accomplish this, the electrochemical membrane reactor (ECMR) is developed by combining membrane filtration and electrochemical advanced oxidation technology. The device configuration and working mode of the electrochemical membrane reactor are introduced and compared. Besides, the principles of the removal of antibiotics by the reactor are explained with emphasis. Furthermore, the commonly used cathode and anode materials of the reactor in the current research are summarized, and the electrode materials are discussed. The effects of selection and modification on the elimination of antibiotics in the reactor and the impact are analysed. To address the limitations of electrochemical membrane reactors, this review proposes that more research should be done in the aspects of antibiotic degradation mechanism, reduction of membrane electrode R&D costs, and actual application of amplification devices.


1992 ◽  
Vol 26 (11) ◽  
pp. 1447-1451 ◽  
Author(s):  
Luciana Frighetto ◽  
Donna Nickoloff ◽  
Shelagh M. Martinusen ◽  
Fatima S. Mamdani ◽  
Peter J. Jewesson

OBJECTIVE: To assess the impact of an intravenous-to-oral (iv-po) stepdown program on the relative use of oral and parenteral dosage forms of select antimicrobials. DESIGN: A retrospective review of drug utilization records before and after a trial comparing metronidazole and clindamycin prescribing trends from a 12-month baseline period to a four-year follow-up period. SETTING: One thousand-bed Canadian tertiary care referral teaching center. INTERVENTION: An authorized iv-po stepdown program was developed to promote the oral route of drug administration. Reminders of iv-po stepdown were produced for metronidazole and clindamycin and these notes were sent to nursing units with the parenteral dosage form. The notes then were attached to the front of the health record to serve as a reminder to prescribers that an equally effective, well-tolerated, and less-expensive oral dosage form was available for use. RESULTS: A 44 percent relative increase in the use of oral metronidazole and a 79 percent relative increase in the use of oral clindamycin occurred. When acquisition and delivery costs were considered, cumulative cost savings from 1988 to 1991 resulted for metronidazole ($31920) and clindamycin ($53880). CONCLUSIONS: This intervention represents a simple yet effective method of promoting a process of stepdown from parenteral to oral antibiotic therapy.


2018 ◽  
Vol 279 ◽  
pp. 64-69 ◽  
Author(s):  
Martin Wagner ◽  
Panos Skandamis ◽  
Franz Allerberger ◽  
Dagmar Schoder ◽  
Caroline Lassnig ◽  
...  

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