Development of a nondestructive assay method using Raman spectroscopy in the pharmaceutical production process of a freeze‐dried injection with gemcitabine as active pharmaceutical ingredient

2021 ◽  
Author(s):  
Jaejin Kim ◽  
Janghee Han ◽  
Young‐Ah Woo
Keyword(s):  
Raman Spectroscopy ◽  
Production Process ◽  
Active Pharmaceutical Ingredient ◽  
Assay Method ◽  
Nondestructive Assay ◽  
Freeze Dried ◽  
Pharmaceutical Production

scholarly journals Low-Content Quantitation in Entecavir Tablets Using 1064 nm Raman Spectroscopy

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yanlei Kang ◽  
Yushan Zhou ◽  
Qiaoyu Wu ◽  
Ning Wang ◽  
Jianguang Zhou
Keyword(s):  
Raman Spectroscopy ◽  
Limit Of Detection ◽  
Pharmaceutical Formulations ◽  
Active Pharmaceutical Ingredient ◽  
Difficult Problem ◽  
Excitation Wavelength ◽  
Standard Normal Variate ◽  
First Choice ◽  
Standard Normal ◽  
Calibration Samples

The nondestructive and high sensitive analysis of a low content of an active pharmaceutical ingredient (API) was a difficult problem, especially in a complex system of pharmaceutical formulations. In this paper, a rapid and no sample preparation method was developed, which used a 1064 nm Raman spectrometer to detect entecavir monohydrate (ETV-H) in Baraclude tablets. Entecavir was a drug approved by FDA for the treatment of chronic hepatitis B and became the first choice in the market. The wavelength selection results displayed that the signal-to-background ratio of the Raman spectrum with 1064 nm excitation wavelength was 14 times that of the commonly used 785 nm wavelength. The partial least squares (PLS) method was used to calibrate concentration models containing 0.1% to 1.0% w/w% ETV-H in calibration set samples. Different preprocessing methods were used to eliminate the background interference and extract more spectral information. Calibration samples were used to choose the best performing model. Then, all the calibration samples combined with the best performing models’ parameters successfully predicted the content of ETV-H in Baraclude tablets. Combining baseline processing and standard normal variate (SNV) with PLS, the model showed a good result with an R2 of 0.973, RMSEC of 0.05%, and RMSEP of 0.03% on the spectral region of 1350–1700 cm−1. The limit of detection of this model was 0.17%. These results showed that 1064 nm Raman spectroscopy technology could be an alternative analytical procedure to quantify low-content API in intact tablets.

scholarly journals Validation of analytical method for determination of furosemide in extemporaneous syrup

2017 ◽  
Author(s):  
D. Alfred-Ugbenbo ◽  
O. A. Zdoryk ◽  
V. A. Georgiyants
Keyword(s):  
Sodium Hydroxide Solution ◽  
Correlation Coefficients ◽  
Active Pharmaceutical Ingredient ◽  
Stability Study ◽  
Assay Method ◽  
Pure Substance ◽  
Ultraviolet Region ◽  
Validation Parameters ◽  
Development And Validation ◽  
Medicinal Drugs

Introduction. Extreme syrups can be manufactured using substances or ready medicinal drugs as the active pharmaceutical ingredient. There is a necessity in the development and validation of analytical methods that can be used for quality control of pharmaceutical manufacturing of syrups containing furosemide.The aim of the study – to develop and validate assay method for furosemide in extemporaneous syrups prepared from both pure substance and finished products. Methods of the research. For proposed UV spectrophotometric assay method the conditions of analysis, sample preparation and validation characteristics were defined. Suspensions of substance and crushed commercial tablets were dissolved in 0.1 M sodium hydroxide solution and evaluated spectrophotometrically in ultraviolet region of light at a wavelength 271 nm using method of specific absorbance.Results and Discussion. Samples comply with the Beer-Lambert Bouguer law within the concentration range of 8×10-3 – 1.2×10-2 mg/ml with correlation coefficients ≥ 0.9981. The uncertainty of the methods was well within the critical value of the error (0.72 %≤ maxΔAs) for both samples of syrup containing pure substance and commercial tablets. Recovery studies for furosemide in syrup samples of substance and crushed commercial tablets yielded 99.92 ±0.54 % and 99.14±0.16 % respectively. Assay limit of ±10 % by the validation parameters: specificity, linearity, precision, accuracy within the range of 80–120 % of the nominal contents was met by all compounded preparations.Conclusions. The results of validation proved that this method can be reproduced correctly and is suitable for use in pharmaceutical analysis. Adoption of this method is planned in evaluating uniformity of content and, in combination of other methods, ascertain chemical stability study of compounded furosemide syrups.

scholarly journals Diagnosis Failure Cause of complex Pharmaceutical System by Bayes Learning for Decision Support

2020 ◽  
Vol 9 (1) ◽  
pp. 5-8 ◽  
Keyword(s):  
Decision Support ◽  
Production Process ◽  
Bayesian Model ◽  
Data Extraction ◽  
Production Quality ◽  
Main Challenge ◽  
Improve Production Quality ◽  
Model Diagnosis ◽  
Pharmaceutical Production ◽  
Graph Form

This work proposes a real application of diagnosis protocol for complex pharmaceutical process drifts. Main challenge is to identify and classify failure causes of production process. The model which we have proposed is structured in the causal graph form, named “Hierarchical Naïve Bayes” (HNB) formalism. Our contribution is the presentation of a methodology that allows developing flexibility in particular complex pharmaceutical production context. A data extraction and processing prototype is performed in this paper from real pharmacy company to build Bayesian model. Diagnosis results are decision support elements that built based on HNB probabilities. Furthermore, this work can be applied in order to improve production quality in businesses competition.

scholarly journals STUDY ON THE PRODUCTION PROCESS OF SINGLE DOSE MEASLES-RUBELLA COMBINED VACCINE AT POLYVAC

2021 ◽  
Vol 62 (4) ◽  
Author(s):  
Nguyen Thuy Huong ◽  
Le Thi Hoa ◽  
Le Quoc Hung ◽  
Ngo Thu Huong ◽  
Nguyen Dang Hien
Keyword(s):  
Single Dose ◽  
Production Process ◽  
Rubella Virus ◽  
Measles Virus ◽  
Sterile Water ◽  
Residual Moisture Content ◽  
Residual Moisture ◽  
Freeze Dried ◽  
Combined Vaccine

Center for Research and Production of Vaccines and Biologicals (POLYVAC) has conducted “Study on the production process of single dose measles-rubella combined vaccine (MRVAC)” (1dose/vial) in lyophilized form to make it convenient to use for vaccination services and export. The results have determined  the formulation of MRVAC final bulk, freeze-dried process. The quality of researched products met WHO and Vietnam Pharmacopoeia V standards in both visual tests of lyophilized vaccine cake and after being reconstituted with sterile water for injection, the titer of measles virus ranges from 4.03 to 4.28 lgPFU/0.5mL and titer of rubella virus is from 3.79 to 3.98 lgPFU/0.5 mL. Results on thermal stability test when incubating the vaccine at 37oC/7days, the titer of measles virus decreased from 0.79 to 0.96 lgPFU/ 0.5mL and titer of rubella virus decreased from 0 to 0.18 lgPFU/0.5mL. Residual moisture content ranges from 0.35 to 0.72%. pH of vaccine is stable, ranges from 7.42 to 7.62.

scholarly journals Lactobacillus rhamnosus GG Genomic and Phenotypic Stability in an Industrial Production Process

2020 ◽  
Vol 86 (6) ◽  
Author(s):  
Marianne Stage ◽  
Anita Wichmann ◽  
Mette Jørgensen ◽  
Natalia Ivonne Vera-Jimenéz ◽  
Malue Wielje ◽  
...  
Keyword(s):  
Production Process ◽  
Gene Cluster ◽  
Industrial Production ◽  
Lactobacillus Rhamnosus ◽  
Probiotic Properties ◽  
Phenotypic Stability ◽  
Content Type ◽  
Freeze Dried ◽  
Probiotic Strains

ABSTRACT Lactobacillus rhamnosus GG is one of the most widely marketed and studied probiotic strains. In L. rhamnosus GG, the spaCBA-srtC1 gene cluster encodes pili, which are important for some of the probiotic properties of the strain. A previous study showed that the DNA sequence of the spaCBA-srtC1 gene cluster was not present in some L. rhamnosus GG variants isolated from liquid dairy products. To examine the stability of the L. rhamnosus GG genome in an industrial production process, we sequenced the genome of samples of L. rhamnosus GG (DSM 33156) collected at specific steps of the industrial production process, including the culture collection stock, intermediate fermentations, and final freeze-dried products. We found that the L. rhamnosus GG genome sequence was unchanged throughout the production process. Consequently, the spaCBA-srtC1 gene locus was intact and fully conserved in all 31 samples examined. In addition, different production batches of L. rhamnosus GG exhibited consistent phenotypes, including the presence of pili in final freeze-dried products, and consistent characteristics in in vitro assays of probiotic properties. Our data show that L. rhamnosus GG is highly stable in this industrial production process. IMPORTANCE Lactobacillus rhamnosus GG is one of the best-studied probiotic strains. One of the well-characterized features of the strain is the pili encoded by the spaCBA-srtC1 gene cluster. These pili are involved in persistence in the gastrointestinal tract and are important for the probiotic properties of L. rhamnosus GG. Previous studies demonstrated that the L. rhamnosus GG genome can be unstable under certain conditions and can lose the spaCBA-srtC1 gene cluster. Since in vitro studies have shown that the loss of the spaCBA-srtC1 gene cluster decreases certain L. rhamnosus GG probiotic properties, we assessed both the genomic stability and phenotypic properties of L. rhamnosus GG throughout an industrial production process. We found that neither genomic nor phenotypic changes occurred in the samples. Therefore, we demonstrate that L. rhamnosus GG retains the spaCBA-srtC1 cluster and exhibits excellent genomic and phenotypic stability in the specific industrial process examined here.

scholarly journals Lactate-dehydrogenase activity in the rat testis: a comparison between fluorometric assay of freeze-dried sections and histochemical localization with phenazine methosulphate.

1978 ◽  
Vol 26 (11) ◽  
pp. 967-972 ◽  
Author(s):  
L Heywood ◽  
A Blackshaw
Keyword(s):  
Lactate Dehydrogenase ◽  
Dehydrogenase Activity ◽  
Fluorometric Assay ◽  
Histochemical Localization ◽  
Assay Method ◽  
Interstitial Tissue ◽  
Lactate Dehydrogenase Activity ◽  
Ldh Activity ◽  
Freeze Dried ◽  
Phenazine Methosulphate

The activity of lactate dehydrogenase (LDH) in freeze-dried sections of rat testes was determined by using a fluorometric assay method and found to be 4.47 +/- 0.23 moles/Kg dry weight/hr (MKDH +/- S.E.M.) in whole sections, 3.31 +/- 0.16 in tubules and 12.0 +/- 1.9 in interstitial tissue. The activities and regional variation are similar to those measured in nervous tissue and are well correlated with the histochemical localization of LDH activity when phenazine methosulphate (PMS) is not used as an electron carrier. LDH and lipoamide dehydrogenase activity have the same histochemical distribution and there is no nonspecific staining with either method. The use of PMS results in reduced dependence on substrate and coenzyme and does not indicate higher interstitial activity but may provide an indication of developing lactate metabolism in maturing sperm. It is recomended that methods with and without PMS be used in studies of LDH activity in the testis.

scholarly journals Uncertainty Quantification in Application of the Enrichment Meter Principle for Nondestructive Assay of Special Nuclear Material

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Tom Burr ◽  
Stephen Croft ◽  
Ken Jarman
Keyword(s):  
Uncertainty Quantification ◽  
Nuclear Material ◽  
Test Method ◽  
Assay Method ◽  
Total Uncertainty ◽  
Nondestructive Assay ◽  
Error Bar ◽  
Mass Estimate ◽  
Gamma Spectra

Nondestructive assay (NDA) of special nuclear material (SNM) is used in nonproliferation applications, including identification of SNM at border crossings, and quantifying SNM at safeguarded facilities. No assay method is complete without “error bars,” which provide one widely used way to express confidence in assay results. NDA specialists typically partition total uncertainty into “random” and “systematic” components so that, for example, an error bar can be developed for the SNM mass estimate in one item or for the total SNM mass estimate in multiple items. Uncertainty quantification (UQ) for NDA has always been important, but greater rigor is needed and achievable using modern statistical methods. To this end, we describe the extent to which the guideline for expressing uncertainty in measurements (GUM) can be used for NDA. Also, we describe possible extensions to the GUM by illustrating UQ challenges in NDA that it does not address, including calibration with errors in predictors, model error, and item-specific biases. A case study is presented using gamma spectra and applying the enrichment meter principle to estimate the235U mass in an item. The case study illustrates how to update the ASTM international standard test method for application of the enrichment meter principle using gamma spectra.

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