scholarly journals Validated Modernized Assay for Foscarnet in Pharmaceutical Formulations Using Suppressed Ion Chromatography Developed through a Quality by Design Approach

Separations ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 209
Author(s):  
Ngoc Phuoc Dinh ◽  
Adel Shamshir ◽  
Gjani Hulaj ◽  
Tobias Jonsson
Keyword(s):  
Ion Chromatography ◽  
Quality By Design ◽  
Drug Product ◽  
Pharmaceutical Formulations ◽  
The United States ◽  
Intermediate Precision ◽  
Precision Data ◽  
Relative Standard ◽  
Suppressed Conductivity Detection ◽  
Quality By Design Approach

Inspired by the United States Pharmacopoeia (USP) “monograph modernization” initiative, we developed and validated an assay for foscarnet sodium injection solution (“foscavir”), following quality by design (QbD) principles, incorporating design of experiments (DoE) and multivariate data analysis to establish the design space and robust setpoint of the method. The resulting analytical procedure was based on ion chromatography (IC) with suppressed conductivity detection, employing an isocratic carbonate–bicarbonate eluent system. The assay was successfully validated at the robust setpoint conditions, according to the guidelines established by the International Council for Harmonization (ICH). The linear range stretched at least from 5 to 100 mg/L with high repeatability (relative standard deviation, RSD ≤ 0.3%) both at the target concentration (60 mg/L) and at 50% and 150% from this level. Special attention was given to establish a rugged assay that would be easily transferable between laboratories, and the recorded recoveries of 98.2–100.5% for both the formulated drug product and the drug substance during intermediate precision evaluation at different analysis situations indicated that this mission was accomplished. A multivariate assessment of intermediate precision data acquired using an experimental design scheme revealed that the assay was not adversely affected by any of the situation variables, including the use of different liquid chromatography instrument types, regardless of if they were constructed from inert materials or stainless steel that had been passivated, even though such problems have been reported in several previous methods for analysis of foscarnet.

scholarly journals Liquid Chromatographic Determination of Methylxanthines and Catechins in Herbal Preparations Containing Guaraná

1998 ◽  
Vol 81 (4) ◽  
pp. 691-701 ◽  
Author(s):  
Marvin Carlson ◽  
Richard D Thompson
Keyword(s):  
Phosphate Buffer ◽  
Chromatographic Determination ◽  
Nutritional Supplement ◽  
The United States ◽  
Precision Data ◽  
Herbal Preparations ◽  
Solid Dosage ◽  
System A ◽  
Relative Standard ◽  
Liquid Chromatographic

Abstract Herbal preparations derived from the dried seeds of guarana (Paullinia cupana) have become a popular nutritional supplement used for stimulatory purposes. Once considered a drug substance in the United States, guaraná currently is classified as a food additive and dietary supplement. The pharmacological activity of guaraná-containing products is primarily due to methylxanthine alkaloids. For guaraná preparations, methylxanthine levels and, more significantly, the presence of several polyphenol compounds (i.e., catechins) provide phytochemical markers of authenticity. Methylxanthines and polyphenols are extracted from sample matrix with a heated phosphate buffer-methanol solution, the cooled extract is filtered, and the extract is injected into the liquid chromatographic (LC) system. A Nova-Pak C18 column eluted with phosphate buffer-methanol mobile phase (pH = 3.50) and monitored at 272 nm gave satisfactory resolution for the methylxanthines theobromine, theophylline, caffeine and the polyphenols (+)-catechin and (−)-epicatechin. Twenty-four products including dried seeds, dried paste, seed powders, tablets, and capsule formulations were assayed and conclusions were drawn about their authenticity. The LC system responded linearly to methylxanthines over the 100-fold range in concentration from 0.043 to 4.30 μg/mL for theobromine and caffeine and from 0.041 to 4.10 μg/mL for theophylline. Precision data for the 3 methylxanthines obtained from 10 different products (n = 5) gave relative standard deviation (RSD) values of 1.18-15.52% within a concentration range of 0.01-52.28 mg/g. Recoveries of methylxanthines from fortified products varied from 87.5 to 120.0%. The response for catechins was linear over a 200-fold range in concentration of 0.05-10.0 μg/mL. Precision data from 5 products (n = 5) gave RSD values of 1.08-5.54% within a concentration range of 0.34-32.65 mg/g. Recoveries from these products ranged from 87.7 to 109.7%. Results and chromatographic profiles for 14 commercial products in solid dosage form indicate that a number of these products may not contain authentic guaraná as an active ingredient or contain less than the declared quantity of guaraná. The proposed procedure also was applied to 2 carbonated soft drinks and a sample of mate.

scholarly journals Determination of Phosphine Residues in Whole Grains and Soybeans by Ion Chromatography via Conversion to Phosphate

1998 ◽  
Vol 81 (6) ◽  
pp. 1190-1201 ◽  
Author(s):  
Marvin Carlson ◽  
Richard D Thompson
Keyword(s):  
Colorimetric Method ◽  
Whole Grains ◽  
Aluminum Phosphide ◽  
Precision Data ◽  
Relative Standard ◽  
Suppressed Conductivity Detection ◽  
Phosphine Residues ◽  
Relationship Of ◽  
The Relationship

Abstract An ion chromatographic (IC) method was developed for determining phosphine (PH3) in whole grains (barley, corn, oats, rice, rye, and wheat) and soybeans. The method converts phosphine to phosphate (i.e., orthophosphate) and isolates the phosphate by IC with eluent-suppressed conductivity detection. Recoveries of unbound phosphine by the method were similar to those obtained by an established colorimetric method for 7 different products fortified at 3 levels. Mean recoveries were low (i.e., 30-60%) and varied with product type and level of fortification. Recoveries of PH3 from previously fumigated products fortified with aluminum phosphide ranged from 19.0% for barley fortified at 0.734 ppm to 88.3% for corn fortified at 1.691 ppm. Precision data from 3 products based on replicate analyses (n = 4 or 5) gave relative standard deviations of 1.78-4.66% for mean laboratory-fumigated PH3 levels of 0.679-1.309 ppm. Estimated limits of detection (LOD) and quantitation (LOQ) for PH3 were 0.010 μg/g (10 ppb) and 0.0275 μg/g (27.5 ppb) at signal-to-noise ratios (S/N) of 4:1 and 10:1, respectively. These values were also determined for a nonchemically suppressed IC system with LOD of 0.02 μg/g (20 ppb) and LOQ of 0.055 μg/g (55 ppb) at S/N of 4:1 and 10:1, respectively. Phosphate response was linear over the concentration range equivalent to 0.30-10.0 fig P/mL, with a mean correlation coefficient of 0.9988 based on replicate standard curves. The relationship of product composition to recovery from various products was also examined.

Development of Topical Nanocarriers for Skin Cancer Treatment Using Quality by Design Approach

2019 ◽  
Vol 26 (35) ◽  
pp. 6440-6458 ◽  
Author(s):  
Erzsébet Csányi ◽  
Mónika Bakonyi ◽  
Anita Kovács ◽  
Mária Budai-Szűcs ◽  
Ildikó Csóka ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Topical Treatment ◽  
Quality By Design ◽  
Drug Carrier ◽  
Treatment Options ◽  
Pharmaceutical Formulations ◽  
Quality Attributes ◽  
Formulation Development ◽  
Quality By Design Approach ◽  
Dermal Administration

Background: One of the most compelling medical challenges of this century is the treatment of cancer and among them, skin cancer is the most common type. Thus, current treatments need to be renewed continuously to handle this challenge. Objective: This review presents considerations which can be employed during the development of nanosized formulations dedicated to the topical treatment of skin cancer. We aimed to collect and organize literature data on the treatment options for skin cancer in order to determine the required quality attributes of an effective dermal anticancer formulation. Method: With the consideration of the Quality by Design (QbD) approach related to the development of new pharmaceutical formulations, a cost-saving process ensuring a high-quality product taking into account patient expectations, industrial and regulatory aspects can be achieved. Furthermore, this concept is highly recommended by regulatory agencies. Results: Our work discusses the current therapies, active agents, drug carrier systems, and evaluation methods in connection with the treatment of skin cancer and outlines Critical Quality Attributes which need to be considered during the development of a nanosized dermal anticancer formulation. Conclusion: The first part of this review summarizes the most important topical treatment therapies for skin cancer and highlights the future therapeutic perspectives, focusing on the benefits of nanotechnology and dermal administration. The second part outlines the critical points of nanosized dermal anticancer formulation development in the view of QbD approach. Our research emphasizes the application of QbD method for a rationalized and more effective anticancer formulation development process.

scholarly journals A fully validated microbiological assay to evaluate the potency of ceftriaxone sodium

2013 ◽  
Vol 49 (4) ◽  
pp. 753-762 ◽  
Author(s):  
Maria Luisa Manfio ◽  
Danielle Araújo Agarrayua ◽  
Jaison Carlosso Machado ◽  
Cleber Alberto Schmidt
Keyword(s):  
Low Cost ◽  
Pharmaceutical Formulations ◽  
Microbiological Assay ◽  
Intermediate Precision ◽  
Chromatography Method ◽  
Beta Lactamases ◽  
Pharmaceutical Samples ◽  
Ceftriaxone Sodium ◽  
Relative Standard ◽  
Liquid Chromatography Method

Ceftriaxone (CFTX) sodium is a third-generation, broad-spectrum cephalosporin that is resistant to beta-lactamases. An alternative bioassay for the assessment of the potency of this drug in pharmaceutical formulations has not been previously reported. Thus, this paper reports the development and full validation of a 3 x 3 agar diffusion bioassay using a cylinder-plate method to quantify CFTX sodium in pharmaceutical samples. The strain Staphylococcus aureus ATCC 6538P was used as the test microorganism, and the results of the proposed bioassay displayed high linearity, precision, accuracy, specificity and robustness. All potency results were statistically analyzed using an analysis of variance (ANOVA) and were found to be linear (r=0.99999) in the range of 16-64 µg/mL, accurate (100.5%), and precise [repeatability: relative standard deviation (RSD)=1.4%; intermediate precision: between-day RSD=2.1% and between-analyst RSD=2.5%]. The specificity of the bioassay was determined by evaluating a degraded sample (50 ºC) at 0, 24 and 48 hours as compared against the results from the pharmacopeial liquid chromatography method for CFTX. The results validated the proposed microbiological assay, which allows reliable quantitation of CFTX in pharmaceutical samples. Moreover, it is a useful, simple and low-cost alternative method for monitoring the quality of this medicine.

scholarly journals Validation of UV Spectrophotometric and Nonaqueous Titration Methods for the Determination of Carvedilol in Pharmaceutical Formulations

2005 ◽  
Vol 88 (5) ◽  
pp. 1299-1303 ◽  
Author(s):  
Carine Viana Silva Ieggli ◽  
Simone Gonçalves Cardoso ◽  
Luziane Potrich Belle
Keyword(s):  
Pharmaceutical Formulations ◽  
The United States ◽  
Violet Crystal ◽  
Relative Standard ◽  
Significant Difference ◽  
Precision And Accuracy ◽  
States Pharmacopeia ◽  
Interday Precision ◽  
Volumetric Methods

Abstract Ultraviolet (UV) spectrophotometric and nonaqueous volumetric methods are described for the determination of carvedilol in pharmaceutical formulations. Linearity, precision, and accuracy were evaluated according to the validation guidelines of the International Conference on Harmonizationand the United States Pharmacopeia for both methods. The UV spectrophotometric procedure was performed in ethanol at 244 nm. Good linearity was obtained between 2 and 7 μg/mL with a correlation coefficient of 0.9999. The intra- and interday precision values were <2% for all samples analyzed. The accuracy, determined from recovery studies, was between 97.5 and 102.2%. The other procedure was based on the volumetric quantitation of carvedilol in a nonaqueous medium with 0.01M perchloric acid and 1% violet crystal as the indicator. The validation of the volumetric method yielded good results that included linearity (r of >0.999), precision (relative standard deviations of <2% for intra- and interday precision), and accuracy (96.4–102.4%). The methods were applied to tablets and compounded capsules. Statistical analysis by analysis of variance showed no significant difference between the results obtained by the proposed methods.

scholarly journals Implementation of Quality by Design for the Development and Validation of Pioglitazone Hydrochloride by RP-UPLC with Application to Formulated Forms

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Cijo M. Xavier ◽  
Kanakapura Basavaiah
Keyword(s):  
Quality By Design ◽  
Pharmaceutical Formulations ◽  
Calibration Graph ◽  
Process Understanding ◽  
Validation Criteria ◽  
Relative Standard ◽  
Level Of Knowledge ◽  
Bulk Drug ◽  
Development And Validation

Quality by Design (QbD) is a philosophy that refines the level of knowledge associated with a product that uses process understanding to deliver a product with the desired critical quality attributes. The objective of this study was to develop an integrated multivariate QbD approach to develop and quantify the constituent concentrations of pioglitazone hydrochloride (PGZ) drug in its pure and formulated forms. To facilitate studies investigating the determination of PGZ in bulk drug and its pharmaceutical formulations, a rapid UPLC method was developed and validated for the determination of PGZ accompanied by its degradation studies in different stress conditions. The method fulfilled validation criteria and was shown to be sensitive, with limits of detection (LOD) and quantitation (LOQ) of 0.01 and 0.05 μg mL−1, respectively. The percent relative standard deviations for robustness and ruggedness were observed within the range of 0.1–1.74. The calibration graph was linear in the range of 0.05–300 μg mL−1. The applicability of the method was shown by analysis of formulated drug samples and spiked human urine. The proposed method can be used for routine analysis in quality controlled laboratories for its bulk and formulated product and this is the first reported UPLC method for the assay of PGZ.

scholarly journals Quality by Design Approach for the Development and Validation of Glipizide, an Antidiabetic Drug, by RP-UPLC with Application to Formulated Forms and Urine

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Cijo M. Xavier ◽  
Kanakapura Basavaiah ◽  
K. B. Vinay ◽  
N. Swamy
Keyword(s):  
Quality Control ◽  
Mobile Phase ◽  
Quality By Design ◽  
Calibration Graph ◽  
Multivariate Approach ◽  
Antidiabetic Drug ◽  
Validation Criteria ◽  
Relative Standard ◽  
Quality By Design Approach ◽  
Development And Validation

Quality by design (QbD) refers to the achievement of certain predictable quality with desired and predetermined specifications. The objective of this study was to develop and demonstrate an integrated multivariate approach to develop and quantify the constituent concentrations of glipizide (GPZ) drug in its pure and tablet forms. The method was developed using Zorbax Extend C-18 (50 mm × 4.6 mm × 1.8 μm) column with mobile phase consisting of a mixture of phosphate buffer of pH 3.5 and acetonitrile (60 : 40 v/v). The method fulfilled validation criteria and was shown to be sensitive, with limits of detection (LOD) and quantitation (LOQ) of 0.001 and 0.005 μg mL−1, respectively. The percentage relative standard deviations for robustness and ruggedness were observed within the range of 0.1 and 0.99. The calibration graph was linear in the range of 0.005–300 μg mL−1. The applicability of the method was shown by the analysis of formulated drug and spiked urine samples. The proposed method can be used for routine analysis in quality control laboratories for its bulk and formulated product, and this is the first UPLC method reported for the assay of GPZ in bulk, formulated form and urine.

Quality by Design in Pharmaceutical Formulation

2019 ◽  
pp. 221-239
Author(s):  
Sundaramurthy Vivekanandan
Keyword(s):  
Quality By Design ◽  
Drug Product ◽  
Quality Attributes ◽  
Pharmaceutical Products ◽  
Design Approach ◽  
Critical Quality Attributes ◽  
Quality Product ◽  
Product Profile ◽  
Critical Material Attributes ◽  
Quality By Design Approach

Quality by design (QbD) is a systematic, scientific, risk-based approach to product development and manufacturing process to consistently deliver the quality product. In this chapter, application, benefits, opportunities, regulatory requirements involved in quality by design of pharmaceutical products are discussed. In quality by design approach, during development, the developer defines quality target product profile (QTPP) and identifies critical quality attributes (CQA). Critical process parameters (CPP) of unit operations which impacts critical quality attributes need to be identified to understand the impact of critical material attributes (CMA) on quality attributes of the drug product. Quality by design approach is defined in ICH guidelines Q8 – Pharmaceutical Development, Q9 – Quality Risk Management, Q10 – Pharmaceutical Quality System. This chapter describes the implementation of new concepts in quality by design like design of experiments to achieve design space, control strategy to consistently manufacture quality product throughout the product lifecycle.

scholarly journals A simple and precise conductometric method for the determination of losartan in pharmaceutical products

2012 ◽  
Vol 10 (6) ◽  
pp. 1842-1849 ◽  
Author(s):  
Pamela Oliveira Rossini ◽  
Fabiana Felix ◽  
Lúcio Angnes
Keyword(s):  
Patent Protection ◽  
Waste Treatment ◽  
Conductometric Titration ◽  
Pharmaceutical Formulations ◽  
The United States ◽  
Pharmaceutical Products ◽  
Attractive Alternative ◽  
Slow Increase ◽  
Relative Standard

AbstractLosartan is an antihypertensive agent that lost its patent protection in 2010, and, consequently, it has been available in generic form. The latter motivated the search for a rapid and precise alternative method. Here, a simple conductometric titration in aqueous medium is described for the losartan analysis in pharmaceutical formulations. The first step of the titration occurs with the protonation of losartan producing a white precipitate and resulting in a slow increase in conductivity. When the protonation stage is complete, a sharp increase in conductivity occurs which was determined to be due to the presence of excess of acid. The titrimetric method was applied to the determination of losartan in pharmaceutical products and the results are comparable with values obtained using a chromatographic method recommended by the United States Pharmacopoeia. The relative standard deviation for successive measurements of a 125 mg L−1 (2.71×10−4 mol L−1) losartan solution was approximately 2%. Recovery study in tablet samples ranged between 99 and 102.4%. The procedure is fast, simple, and represents an attractive alternative for losartan quantification in routine analysis. In addition, it avoids organic solvents, minimizes the risk of exposure to the operator, and the waste treatment is easier compared to classical chromatographic methods.

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