scholarly journals Impact of Critical Material Attributes (CMAs)-Particle Shape on Miniature Pharmaceutical Unit Operations

2021 ◽  
Vol 22 (3) ◽  
Author(s):  
Mohammad A. Azad ◽  
Gerard Capellades ◽  
Allison B. Wang ◽  
David M. Klee ◽  
Gregory Hammersmith ◽  
...  
Keyword(s):  
Drug Product ◽  
The United States ◽  
Pharmaceutical Drugs ◽  
Critical Material ◽  
Unit Operations ◽  
Custom Made ◽  
Critical Material Attributes ◽  
Powder Properties ◽  
Tablet Manufacturing ◽  
States Pharmacopeia

AbstractThe U.S. Food and Drug Administration (FDA) emphasizes drug product development by Quality by Design (QbD). Critical material attributes (CMAs) are a QbD element that has an impact on pharmaceutical operations and product quality. Pharmaceutical drugs often crystallize as needle-shaped (a CMA) particles and affect the process due to poor flowability, low bulk density, and high compressibility, and eventually the product performance. In this study, the product obtained from crystallization was needle-shaped Ciprofloxacin HCl (CIPRO), formed lumps during drying, and compacted during processing through feeders. To delump small amounts of materials and break the needles, multiple available devices (mortar-pestle, Krups grinder) and custom-made grinder were assessed before formulation. The processed CIPRO powder was then used to make tablets in the miniature tablet manufacturing unit developed by the team at MIT. The critical quality attributes (CQA) of the tablets, set by the United States Pharmacopeia (USP), were then assessed for the drug powder processed with each of these devices. Powder properties comparable to commercial CIPRO were obtained when the custom MIT-designed grinder was used, leading to tablets that meet the USP criteria, with comparable dissolution profiles of those for marketed CIPRO tablets. This study demonstrates how needle-shaped crystals have an impact on pharmaceutical operations, even if it is on a miniature scale, and how proper shape and subsequent flow properties can be obtained by processing the particles through the MIT team-designed grinder. Graphical Abstract

A Comparison of Heparin Potency Estimates Obtained by Activated Partial Thromboplastin Time and British Pharmacopoeial Assays

1985 ◽  
Vol 53 (01) ◽  
pp. 116-117 ◽  
Author(s):  
R E Merton ◽  
A D Curtis ◽  
D P Thomas
Keyword(s):  
United States ◽  
Partial Thromboplastin Time ◽  
Close Agreement ◽  
The United States ◽  
Activated Partial Thromboplastin Time ◽  
United States Pharmacopeia ◽  
International Unit ◽  
British Pharmacopoeia ◽  
States Pharmacopeia ◽  
Heparin Preparation

SummaryHeparin samples from five manufacturers were assayed by the revised British Pharmacopoeia (BP) heparin assay and the results compared with those obtained using the activated partial thromboplastin time (APTT) assay. The United States Pharmacopeia (USP) reference heparin preparation and the 4th International Standard (IS) for heparin were also assayed by the two methods relative to the 3rd IS. The results obtained by the revised BP assay were in close agreement with those obtained by the APTT assay for all the heparins that were tested. The assays revealed that there is at least a 10% discrepancy between the International Unit for heparin and the USP unit.

scholarly journals High Temperatures Decrease the Flight Capacity of Diaphorina citri Kuwayama (Hemiptera: Liviidae)

Insects ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 394
Author(s):  
Carlos A. Antolinez ◽  
Tobias Moyneur ◽  
Xavier Martini ◽  
Monique J. Rivera
Keyword(s):  
Relative Humidity ◽  
High Temperatures ◽  
Insect Pest ◽  
The United States ◽  
Diaphorina Citri ◽  
Long Distance ◽  
Flight Duration ◽  
Custom Made ◽  
Flight Capacity ◽  
Low Humidity

Diaphorina citri Kuwayama (Hemiptera: Liviidae), commonly known as Asian citrus psyllid (ACP), is an invasive insect pest and the vector of the bacterium causing Huanglongbing (HLB), a lethal disease of citrus. In the United States, ACP has been established in all citrus-producing zones, all of which have different environmental conditions. The spread of ACP and, more importantly, HLB, has progressed differently depending on the state, with more rapid spread in Florida and Texas than in California. Climatic variations between the regions are likely a strong factor in the difference in the rate of spread. Despite this, it is unknown how the flight capacity of D. citri is influenced by high temperatures (>30 °C) and subsequently, low humidity experienced in California but not in Texas or Florida. In this study, by using a custom-made, temperature-controlled flight mill arena, we assessed the effect of high temperatures on the flight capacity and flight propensity of D. citri under low (20–40%) and high (76–90%) relative humidity conditions. We found that temperature and humidity influence the propensity to engage in short or long-distance flight events. Psyllids exposed to temperatures above 43 °C only performed short flights (˂60 s), and a high relative humidity significantly decrease the proportion of long flights (≥60 s) at 26 and 40 °C. The flight capacity for insects who engaged in short and long flights was significantly affected by temperature but not by humidity. For long flyers, temperature (in the 26–43 °C range) was negatively correlated with distance flown and flight duration. The most favorable temperature for long dispersion was 26 °C, with suboptimal temperatures in the range of 32–37 °C and the least favorable temperatures at 40 and 43 °C. In conclusion, D. citri is able to fly in a broad range of temperatures and efficiently fly in high and low humidity. However, temperatures above 40 °C, similar to those experienced in semi-arid environments like Southern California or Arizona, are detrimental for its flight capacity.

scholarly journals 1593. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against OXA-48 β-lactamase–Producing Enterobacterales Collected in International Medical Centers, Including the United States, in 2017–2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S793-S793
Author(s):  
Lynn-Yao Lin ◽  
Dmitri Debabov ◽  
William Chang
Keyword(s):  
Antimicrobial Agents ◽  
The United States ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Multiple Resistance ◽  
In Vitro Susceptibility ◽  
Medical Centers ◽  
Custom Made

Abstract Background OXA-48 is a carbapenemase with low-level hydrolytic activity toward cephalosporins. This study evaluated in vitro activities of ceftazidime-avibactam (CAZ-AVI), meropenem (MEM), meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T), and other antimicrobial agents against 113 OXA-48-producing Enterobacterales with multiple resistance mechanisms collected in a 2017–2018 global surveillance program. Methods Nonduplicate clinical isolates of 113 Enterobacterales were collected from medical centers in 25 countries in 2017–2018. In vitro susceptibility tests were performed by broth microdilution with a custom-made panel consisting of CAZ-AVI, ceftazidime (CAZ), MEM, MVB, C/T, colistin (COL), gentamicin (GEN), levofloxacin (LEV), and amikacin (AMK). Whole genome sequencing or quantitative PCR data were used to analyze resistance mechanisms, such as OXA-48, extended-spectrum β-lactamase (ESBL), original-spectrum β-lactamase (OSBL), and AmpC β-lactamase. Clinical and Laboratory Standards Institute breakpoints were applied for susceptibility interpretations. Results Of 113 OXA-48–producing clinical isolates, 20 carried OXA-48 alone. The remaining 93 isolates carried additional β-lactamases, including 63 with ESBL (CTX-M-15) + OSBL (SHV, TEM), 15 with AmpC (DHA, AAC, CMY) + ESBL (CTX-M-15), and 15 with OSBL (SHV, TEM). 99.1% (all but 1) of all isolates tested were susceptible to CAZ-AVI, whereas 71.7%, 17.7%, and 14.2% were susceptible to MVB, MEM, and C/T, respectively. Among isolates harboring multiple resistance mechanisms (OXA-48 + ESBL + OSBL; n=63), 98.4%, 69.8%, 11.1%, and 7.9% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively. Among isolates carrying OXA-48 + AmpC + ESBL + OSBL (n=15), 100%, 66.7%, 13.3%, and 13.3% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively (Table). Aminoglycosides (AMK and GEN) and other β-lactams (eg, CAZ) were 20%–90% active against these isolates. COL was the second most effective comparator, inhibiting 83.2% of these isolates. Table Conclusion CAZ-AVI was the most effective agent in this study compared with other antibiotics, including β-lactams, β-lactam–β-lactamase inhibitor combinations, aminoglycosides, and COL, against OXA-48-producing Enterobacterales carrying multiple β-lactamases. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee)

scholarly journals Determination of the melting temperature, heat of fusion, and purity analysis of different samples of zidovudine (AZT) using DSC

2010 ◽  
Vol 46 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Adriano Antunes Souza Araújo ◽  
Marília dos Santos Bezerra ◽  
Sílvia Storpirtis ◽  
Jivaldo do Rosário Matos
Keyword(s):  
The United States ◽  
Raw Material ◽  
Heat Of Fusion ◽  
Average Value ◽  
Purity Analysis ◽  
Temperature Heat ◽  
Chemical Purity ◽  
Dsc Curves ◽  
States Pharmacopeia

The determination of chemical purity, melting range, and variation of enthalpy in the process of characterizing medicines is one of the principal requirements evaluated in quality control of the pharmaceutical industry. In this study, the method of purity determination using DSC was outlined, as well as the application of this technique for the evaluation of commercial samples of zidovudine (AZT) (raw material) supplied by different laboratories. To this end, samples from six different laboratories (A, B, C, D, E, and F) and the standard reference (R) from the United States Pharmacopeia (USP) were analyzed. The DSC curves were obtained in the temperature range of 25 to 200 ºC under the dynamic atmosphere of N2 (50 mL min-1), heating rate of β=2 ºC min-1, using an Al capsule containing approximately 2 mg of sample material. The results demonstrated that the standard reference presented a proportion of 99.83% whereas the AZT samples presented a variation ranging from 97.59 to 99.54%. In addition, the standard reference was found to present a temperature of onset of melting point of 122.80 °C. Regarding the samples of active agents provided by the different laboratories, a variation ranging from 118.70 to 122.87 °C was measured. In terms of ΔHm, the samples presented an average value of 31.12 kJ mol-1.

Assessment of critical material attributes of polyethylene oxide for formulation of prolonged-release tablets

2019 ◽  
Vol 45 (12) ◽  
pp. 1949-1958
Author(s):  
Petra Draksler ◽  
Biljana Janković ◽  
Zrinka Abramović ◽  
Zoran Lavrič ◽  
Anton Meden
Keyword(s):  
Polyethylene Oxide ◽  
Prolonged Release ◽  
Critical Material ◽  
Critical Material Attributes

scholarly journals Stability-Indicating Photochemical Method for the Assay of Thiamine by Spectrophotometry

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Iqbal Ahmad ◽  
Syed Haider Abbas ◽  
Zubair Anwar ◽  
Muhammad Ali Sheraz ◽  
Sofia Ahmed ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
The United States ◽  
Limit Of Quantification ◽  
Chromatography Method ◽  
Stability Indicating ◽  
Low Concentrations ◽  
Photochemical Method ◽  
Significant Difference ◽  
Liquid Chromatography Method ◽  
States Pharmacopeia

A stability-indicating photochemical method has been developed for the assay of thiamine (TH) salts in aqueous solution and in fresh and aged vitamin preparations. It is based on the photooxidation of TH by UV irradiation to form thiochrome (TC) in alkaline solution. The TC : TH ratio under controlled conditions of light intensity, temperature, pH, exposure time, and irradiation distance is constant and can be used to determine the concentration of UV irradiated TH solutions. TC, on extraction with isobutanol from the photodegraded solution of TH, has been determined by the UV spectrophotometric method at 370 nm. It exhibits a high intensity of absorption in the UV region that can be used for the assay of even low concentrations of TH. Under optimum conditions, Beer’s law is obeyed in the concentration range of 0.20–2.00 mg/100 ml (R2 = 09998). The limit of detection (LOD) and limit of quantification (LOQ) are 0.0076 and 0.0231 mg/100 ml, respectively. The method has been validated and applied to aqueous solutions and vitamin preparations. The results have statistically been compared with the United States Pharmacopeia liquid chromatography method. It has been found that there is no significant difference between the two methods at 95% confidence level.

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