Insufficient Stability of Clavulanic Acid in Widely Used Child-Appropriate Formulations

Amoxicillin-clavulanic acid (AMC) belongs to the WHO Essential Medicines List for children, but for optimal antimicrobial effectiveness, reconstituted dry powder suspensions need to be stored in a refrigerated environment. Many patients in low- and middle-income countries who are sold AMC suspensions would be expected not to keep to the specified storage conditions. We aimed to assess the stability of both ingredients in liquid formulations and dispersible tablets, combined with nationally representative data on access to appropriate storage. Degradation of amoxicillin (AMX) and clavulanic-acid (CLA) was measured in suspensions and dispersible tablets commercially available in Switzerland at different ambient temperatures (8 °C vs. 28 °C over 7 days, and 23 °C vs. 28 °C over 24 h, respectively). Data on access to refrigeration and electricity were assessed from the USAID-funded Demographic and Health Survey program. In suspensions, CLA degraded to a maximum of 12.9% (95% CI −55.7%, +29.9%) at 8°C and 72.3% (95% CI −82.8%, −61.8%) at a 28 °C ambient temperature during an observation period of 7 days. Dispersible tablets were observed during 24 h and CLA degraded to 15.4% (95% CI −51.9%, +21.2%) at 23 °C and 21.7% (−28.2%, −15.1%) at a 28 °C ambient temperature. There is relevant degradation of CLA in suspensions during a 7-day course. To overcome the stability challenges for all active components, durable child-appropriate formulations are needed. Until then, prescribers of AMC suspensions or pharmacists who sell the drug need to create awareness for the importance of proper storage conditions regarding effectiveness of both antibiotics and this recommendation should be reflected in the WHO Essential Medicines List for children.

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Access to WHO Essential Medicines for Childhood Cancer Care in Trinidad and Tobago: A Health System Analysis of Barriers and Enablers

JCO Global Oncology ◽

10.1200/jgo.19.00300 ◽

2020 ◽

pp. 67-79 ◽

Cited By ~ 1

Author(s):

Brandon Tang ◽

Curt Bodkyn ◽

Sumit Gupta ◽

Avram Denburg

Keyword(s):

Trinidad And Tobago ◽

Childhood Cancer ◽

Cancer Care ◽

System Analysis ◽

Essential Medicines ◽

Middle Income ◽

Essential Medicines List ◽

Mixed Methods Case Study ◽

Relevant Evidence ◽

Context Specific

PURPOSE Improving access to essential medicines is necessary to reduce global mortality resulting from childhood cancer. However, there is a lack of context-specific data in many low- to middle-income countries on the determinants of access to essential childhood cancer medicines. We conducted a mixed-methods case study of the barriers to and enablers of access to WHO essential medicines for childhood cancer care in Trinidad and Tobago, in response to domestic calls for policy attention and reform. METHODS We interviewed stakeholders (N = 9) across the pharmaceutical supply system using a novel analytic framework and qualitative interview guide. Interviews were recorded, transcribed, and analyzed with constant comparative methods to capture emergent themes. Quantitatively, we examined alignment of the national essential medicines list with the 2017 WHO Essential Medicines List for Children (EMLc). National buyer prices for EMLc cancer medicines were compared with median international prices, with calculation of median price ratios to assess procurement efficiency. RESULTS Principal barriers identified included a lack of data-driven procurement, low supplier incentive to engage in tenders, reactive rather than proactive processes in response to stockouts, and siloed information systems. Recurring themes of regionalization, standardization, and proactivity emerged as priorities for policy reform. Quantitative analysis of the national essential medicines list and median price ratios for procured medicines aligned with findings reported qualitatively. CONCLUSION Our study contributes to global efforts to improve childhood cancer care by identifying policy-relevant evidence on access to essential childhood cancer medicines and providing a model for future studies in other jurisdictions.

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Impact of delays to incubation and storage temperature on blood culture results: a multi-centre study

BMC Infectious Diseases ◽

10.1186/s12879-021-05872-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Clare L. Ling ◽

Tamalee Roberts ◽

Sona Soeng ◽

Tomas-Paul Cusack ◽

David A. B. Dance ◽

...

Keyword(s):

Blood Culture ◽

Storage Temperature ◽

Storage Conditions ◽

Significant Loss ◽

Blood Cultures ◽

Multi Centre Study ◽

Middle Income ◽

Ambient Temperatures ◽

Different Temperatures ◽

Pathogen Recovery

Abstract Background Blood cultures are one of the most important tests performed by microbiology laboratories. Many hospitals, particularly in low and middle-income countries, lack either microbiology services or staff to provide 24 h services resulting in delays to blood culture incubation. There is insufficient guidance on how to transport/store blood cultures if delays before incubation are unavoidable, particularly if ambient temperatures are high. This study set out to address this knowledge gap. Methods In three South East Asian countries, four different blood culture systems (two manual and two automated) were used to test blood cultures spiked with five common bacterial pathogens. Prior to incubation the spiked blood culture bottles were stored at different temperatures (25 °C, in a cool-box at ambient temperature, or at 40 °C) for different lengths of time (0 h, 6 h, 12 h or 24 h). The impacts of these different storage conditions on positive blood culture yield and on time to positivity were examined. Results There was no significant loss in yield when blood cultures were stored < 24 h at 25 °C, however, storage for 24 h at 40 °C decreased yields and longer storage times increased times to detection. Conclusion Blood cultures should be incubated with minimal delay to maximize pathogen recovery and timely result reporting, however, this study provides some reassurance that unavoidable delays can be managed to minimize negative impacts. If delays to incubation ≥ 12 h are unavoidable, transportation at a temperature not exceeding 25 °C, and blind sub-cultures prior to incubation should be considered.

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O25 Clavulanate stability in child-appropriate formulations is inadequate for use in treating young children in Asia

Archives of Disease in Childhood ◽

10.1136/archdischild-2019-esdppp.25 ◽

2019 ◽

Vol 104 (6) ◽

pp. e11.1-e11

Author(s):

I Mack ◽

M Sharland ◽

S Rehm ◽

K Rentsch ◽

J Bielicki

Keyword(s):

Antibiotic Consumption ◽

Storage Conditions ◽

Asian Countries ◽

Middle Income ◽

Ambient Temperatures ◽

Middle Income Countries ◽

Oral Amoxicillin ◽

Amoxicillin Clavulanate ◽

Nationally Representative ◽

Temperature Storage

BackgroundAmoxicillin-clavulanate (AMC) is among the most frequently used antibiotic for paediatric infections globally. AMC child-appropriate formulations are largely limited to dry powder suspensions, which have to be stored refrigerated once reconstituted due to stability limitations of clavulanate.MethodsOral Amoxicillin (AMX) and AMC formulations were identified from IQVIA-MIDAS wholesale data, and 2015 antibiotic consumption in courses/1000 child-years was estimated in Bangladesh, India, Indonesia, Pakistan, Philippines and Vietnam with an assumed average treatment of 7 days. Costs per course in US-$ standardised to 2015 were estimated from the same dataset. Nationally representative data on access to a refrigerator was extracted from the Demographic & Health Surveys Program. Degradation under different temperature conditions of two different AMC suspensions commercially available in Switzerland was tested. Average degradation (three bottles of each product) was measured during 8 days with ambient temperatures of 8°C versus 28°C.ResultsIn India and Pakistan more AMC than AMX courses were sold. In all countries AMC was at least twice and up to 10 times as expensive as AMX. Access to refrigeration was below 45%, even in countries with a high number of sold AMC courses (compared with AMX). In the evaluated co-formulated products, clavulanate showed a maximum degradation of 34% at 8°C, and 73% at 28°C after 8 days. AMX was largely stable at 8°C but 13% degraded at 28°C after 8 days.ConclusionsOral amoxicillin-clavulanate suspensions are widely used in six Asian countries classified as middle-income countries by the World Bank. In reconstituted liquid AMC formulations, neither component is satisfactorily stable at room temperature. Storage conditions for stability are likely inadequate for AMC in many households in the six Asian countries of interest.Disclosure(s)Nothing to disclose

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Desiccation Tolerance of Adult Stem Cells in the Presence of Trehalose and Glycerol

The Open Biotechnology Journal ◽

10.2174/1874070700802010211 ◽

2008 ◽

Vol 2 (1) ◽

pp. 211-218 ◽

Cited By ~ 4

Author(s):

Surbhi Mittal ◽

Ram V. Devireddy

Keyword(s):

Stem Cells ◽

Ambient Temperature ◽

Adult Stem Cells ◽

Membrane Integrity ◽

Storage Conditions ◽

Adipose Derived Stem Cells ◽

Ambient Temperatures ◽

Plastic Bags ◽

Drying Rates ◽

And Storage

Development of protocols for storing desiccated cells at ambient temperatures offers tremendous economic and practical advantages over traditional storage procedures like cryopreservation and freeze-drying. As a first step for developing such procedures for adult stem cells, we have measured the post-rehydration membrane integrity (PRMI) of two passages, Passage-0 (P0) and Passage-1 (P1), of human adipose-derived stem cells (ASCs). ASCs were dried using a convective stage at three different drying rates (slow, moderate and rapid) in D-PBS with trehalose (50 mM) and glycerol (384 mM). ASCs were incubated in the drying media for 30 mins prior to drying at the prescribed rate on the convective stage for 30 mins. After drying, the ASCs were stored for 48 hrs in three different conditions: i) at ambient temperature, ii) in plastic bags at ambient temperature and iii) in vacuum sealed plastic bags at ambient temperature. PRMI was assessed after incubating the rehydrated ASCs with stromal medium for a further 48 hrs. Our measurements show that the PRMI of ASCs was: i) higher when ASCs were dried slowly; ii) increased when they were stored in vacuum as opposed to at ambient or in plastic bags; and iii) decreased with increasing passage of ASCs, i.e. under similar drying and storage conditions P0 ASCs had higher PRMI than P1 ASCs. Our results suggest that the best PRMI (37% for P0 ASCs and ~14% for P1 ASCs) can be achieved when the ASCs were dried slowly and stored in vacuum.

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Estimating global trends in total and childhood antibiotic consumption, 2011-2015

BMJ Global Health ◽

10.1136/bmjgh-2018-001241 ◽

2019 ◽

Vol 4 (1) ◽

pp. e001241 ◽

Cited By ~ 6

Author(s):

Charlotte Jackson ◽

Yingfen Hsia ◽

Julia A Bielicki ◽

Sally Ellis ◽

Peter Stephens ◽

...

Keyword(s):

Clavulanic Acid ◽

Antibiotic Use ◽

Antibiotic Consumption ◽

Essential Medicines ◽

Middle Income ◽

Global Trends ◽

Routine Surveillance ◽

Rate Of Increase ◽

Changes Over Time ◽

Total Sales

IntroductionUnderstanding patterns of antibiotic consumption is essential to ensure access to appropriate antibiotics when needed and to minimise overuse, which can lead to antibiotic resistance. We aimed to describe changes in global antibiotic consumption between 2011 and 2015.MethodsWe analysed wholesale data on total antibiotic sales and antibiotics sold as child-appropriate formulations (CAFs), stratified by country income level (low/middle-income and high-income countries (LMICs and HICs)). The volume of antibiotics sold per year was recorded for 36 LMICs and 39 HICs, measured in standard units (SU: 1 SU is equivalent to a single tablet, capsule or 5 mL ampoule/vial/oral suspension) and SU per person, overall and as CAFs. Changes over time were quantified as percentage changes and compound annual growth rates in consumption per person. Analyses were conducted separately for total sales, sales of antibiotics in the Access and Watch groups of the WHO’s Essential Medicines List for children 2017, for amoxicillin and amoxicillin with clavulanic acid.ResultsAntibiotic consumption increased slightly between 2011 and 2015, from 6.85×1010 SU to 7.44×1010 SU overall and from 1.66×1010 SU to 1.78×1010 SU for CAFs. However, trends differed between countries and for specific antibiotics; for example, consumption of amoxicillin as CAFs changed little in LMICs and HICs, but that of amoxicillin with clavulanic acid increased by 6.8% per year in LMICs and decreased by 1.0% per year in HICs.ConclusionsAs measured in standard units in sales data, the rate of increase in global antibiotic consumption may be slowing. However, the trends appear to differ between countries and drugs. In the absence of routine surveillance of antibiotic use in many countries, these data provide important indicators of trends in consumption which should be confirmed in national and local studies of prescribing.

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FORMULATION AND DEVELOPMENT OF FAST DISSOLVING TABLET OF METOCLOPRAMIDE: AN ANTI-EMETIC DRUG

Journal of Biomedical and Pharmaceutical Research ◽

10.32553/jbpr.v8i6.699 ◽

2019 ◽

Vol 8 (6) ◽

Author(s):

Avilash Carpenter ◽

M.K. Gupta ◽

Neetesh Kumar Jain ◽

Urvashi Sharma ◽

Rahul Sisodiya

Keyword(s):

Mechanical Strength ◽

Standard Procedure ◽

Flow Property ◽

Storage Conditions ◽

Angle Of Repose ◽

Dissolution Time ◽

Disintegration Time ◽

Powder Blend ◽

Standard Curve ◽

The Stability

Aim: The main of the study is to formulate and develop orally disintegrating fast dissolving tablet of Metoclopramide hydrochloride. Material & Methods: Before formulation and development of selected drug, the standard curve in buffer was prepared and absorbance at selected maxima was taken. Then two different disintegrating agents were selected and drug was mixed with disintegrating agents in different ratio. Various Preformulation parameters and evaluation of tablet i.e. disintegration time, dissolution time, friability, hardness, thickness were measured by standard procedure. Result & Discussion: The angle of repose for all the batches prepared. The values were found to be in the range of 30.46 to 36.45, which indicates good flow property for the powder blend according to the USP. The bulk density and tapped density for all the batches varied from 0.49 to 0.54 g/mL and 0.66 to 0.73, respectively. Carr’s index values were found to be in the range of 23.33 to 25.88, which is satisfactory for the powders as well as implies that the blends have good compressibility. Hausner ratio values obtained were in the range of 1.22 to 1.36, which shows a passable flow property for the powder blend based on the USP. The results for tablet thickness and height for all batches was found to range from 4.45 to 4.72 mm and 3.67 to 3.69 mm, respectively. Hardness or breaking force of tablets for all batches was found to range from 32.8 to 36.2 N. Tablet formulations must show good mechanical strength with sufficient hardness in order to handle shipping and transportation. Friability values for all the formulations were found to be in the range of 0.22 % to 0.30 %. Conclusion: Orally disintegrating tablets were compressed in order to have sufficient mechanical strength and integrity to withstand handling, shipping and transportation. The formulation was shown to have a rapid disintegration time that complied with the USP (less than one minute). The data obtained from the stability studies indicated that the orally disintegrating mini-tablets of MTH were stable under different environmental storage conditions. Keywords: Formulation & Development, Fast Dissolving Tablet, Metoclopramide, Anti-Emetic Drug, Oral Disintegrating Tablet

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Nuts, anchor, self-locking, fixed, single lug, reduced series, with counterbore, with MJ threads, classifications: 1100 MPa (at ambient temperatures)/235°C, 1100 MPa (at ambient temperature)/315°C, 1100 MPa (at ambient temperature)/425°C. Dimensions

10.3403/01640506u ◽

2015 ◽

Keyword(s):

Ambient Temperature ◽

Ambient Temperatures

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Mixing Oil-Based Microencapsulation of Garlic Essential Oil: Impact of Incorporating Three Commercial Vegetable Oils on the Stability of Emulsions

Foods ◽

10.3390/foods10071637 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1637

Author(s):

Yunjiao Zhao ◽

Rui Liu ◽

Cuiping Qi ◽

Wen Li ◽

Mohamed Rifky ◽

...

Keyword(s):

Essential Oil ◽

Vegetable Oils ◽

Encapsulation Efficiency ◽

Ostwald Ripening ◽

Corn Oil ◽

Whey Protein Concentrate ◽

Diallyl Disulfide ◽

Active Components ◽

The Stability ◽

Garlic Essential Oil

The active components in garlic essential oil are easily degradable, which limits its application in the food industry. Vegetable oils (VOs) were used to improve the stability of garlic essential oil (GEO) emulsion. The volatile compounds of GEO and its mixtures with vegetable oils (VOs), including corn oil (CO), soybean oil (SO), and olive oil (OO) indicated that GEO-VO mixtures had a higher percentage of Diallyl disulfide and Diallyl trisulfide than pure GEO. Adding an appropriate amount of VOs promoted the GEO emulsion (whey protein concentrate and inulin as the wall materials) stability in order of CO > SO > OO. Evaluation of the encapsulation efficiency, controlled release, and antimicrobial activity of GEO-VO microcapsules showed that the GEO was successfully entrapped and slowly released with active antibacterial activities on both E. coli and S. aureus. Collectively, these results implied that VOs, especially for 20% CO, improved the stability of GEO emulsions and the encapsulation efficiency of GEO microcapsules. The mechanism might be related to (1) the regulating effect of density difference between oil and water phases on prevention to gravitational separation, (2) the promotion to the compatibility of GEO and VOs to inhibit the phase separation caused by Ostwald ripening.

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Influence of Ambient Temperature on Radiative and Convective Heat Dissipation Ratio in Polymer Heat Sinks

Polymers ◽

10.3390/polym13142286 ◽

2021 ◽

Vol 13 (14) ◽

pp. 2286

Author(s):

Jan Kominek ◽

Martin Zachar ◽

Michal Guzej ◽

Erik Bartuli ◽

Petr Kotrbacek

Keyword(s):

Heat Transfer ◽

Ambient Temperature ◽

Convective Heat ◽

Heat Dissipation ◽

High Surface ◽

Heat Sinks ◽

Fourth Power ◽

Molding Process ◽

Ambient Temperatures ◽

University Of Technology

Miniaturization of electronic devices leads to new heat dissipation challenges and traditional cooling methods need to be replaced by new better ones. Polymer heat sinks may, thanks to their unique properties, replace standardly used heat sink materials in certain applications, especially in applications with high ambient temperature. Polymers natively dispose of high surface emissivity in comparison with glossy metals. This high emissivity allows a larger amount of heat to be dissipated to the ambient with the fourth power of its absolute surface temperature. This paper shows the change in radiative and convective heat transfer from polymer heat sinks used in different ambient temperatures. Furthermore, the observed polymer heat sinks have differently oriented graphite filler caused by their molding process differences, therefore their thermal conductivity anisotropies and overall cooling efficiencies also differ. Furthermore, it is also shown that a high radiative heat transfer leads to minimizing these cooling efficiency differences between these polymer heat sinks of the same geometry. The measurements were conducted at HEATLAB, Brno University of Technology.

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