Pharmaceutical Equipment Surfaces Research Articles

Microextraction Recovery of Tilmicosin Phosphate for HPLC-UV Determination in Washings from Surfaces of Pharmaceutical Equipment

Microextraction Recovery of Tilmicosin Phosphate for HPLC-UV Determination in Washings from Surfaces of Pharmaceutical Equipment

Automated Anomaly Detection for Surface Defects by Dual Generative Networks With Limited Training Data

The manufacturing process in the pharmaceutical industry requires for using vessels or tanks which inner surfaces can undergo fouling and/or may develop visible defects that have to be cleaned away. Surface contamination can present itself in different forms, and there is no available image database of stains. In this paper, we propose to use an unsupervised anomaly detection approach which trains models on one or just a few images of clean surfaces. First, we propose an inpainting GAN with global and local generators to make full use of every single image and to reduce the overfitting caused by a limited number of images in the training dataset. Furthermore, we propose a periodic noise injection technique to increase the number of images for training and to improve the detection performance of the network. The experimental results demonstrate that the proposed network and noise injection technique achieve significant performance gains in the challenging task of anomaly detection on the surfaces of pharmaceutical equipment and other real-world industrial datasets. We also consider possible generalizations of the proposed method.

DETERMINATION OF FAVIPIRAVIR RESIDUES ON THE SURFACES OF PHARMACEUTICAL MANUFACTURING EQUIPMENT BY HPLC, LUMINESCENCE AND SPECTROPHOTOMETRY

Determination of active pharmaceutical ingredients (APIs) in washes from the surface of pharmaceutical equipment is necessary to prevent cross-contamination of the next batch of products. Highly sensitive methods of chromatographic (HPLC), luminescent (Lum) and spectrophotometric (SF) determination of antiviral drug favipivir (FAV) residues in washes during cleaning of pharmaceutical equipment have been developed. Chromatographic and luminescence recording conditions of favipiravir were optimized. The content of FAV in the washes (μg/wash) is determined according to the calibration curve. The proposed methods are validated by the following parameters: specificity, linearity, accuracy, limit of detection and limit of quantification. The coefficients of linear dependences in the studied concentration ranges correspond to the permissible values for the methods of determination of substances whose concentration in the sample is above the limit of quantitative determination. Calibration graphs are presented in concentration ranges 0.02-2.0 μg ml (HPLC), 0.3-3.5 μg/ ml (Lum) and 1.0-20.0 μg/ml (SP), the detection limits are 0.023 μg/ml, 0.12 μg/ml and 0.11 μg/ml, respectively. The degree of extraction of favipivir from applicators and surfaces of pharmaceutical equipment is more than 85 %. Luminescent and SP techniques have a number of advantages over HPLC: less complexity, expressiveness and lower consumption of reagents, while the HPLC method has a greater sensitivity. The developed methods can be recommended for determination of residual amounts of favipivir at quality control of cleaning of the pharmaceutical equipment.

Luminescent determination of residues of trazodon hydrochloride and melatonin after cleaning pharmaceutical equipment

A prerequisite for ensuring the quality of medicines is their production in accordance with the rules of GMP (Good Manufacturing Practice for Medicinal Products), one of the most important requirements of which is equipment cleaning. In many cases, the same equipment is used in the production of various preparations. Therefore, to prevent contamination of each of the following drugs, the previous one, it is very important to carry out an effective equipment cleaning procedure with a mandatory assessment of its purity.
 The purpose of this study was to develop simple, express, selective methods for luminescent determination of residual quantities of APIs of trazodone hydrochloride (TG) and melatonin (MT) in washes to control the completeness of their removal when cleaning process equipment.
 The excitation and luminescence spectra were recorded using a Cary Eclipse "Varian" spectrofluorimeter (Australia) with a xenon lamp 150 W. Electronic absorption spectra were recorded on a UV-2401 PC spectrophotometer «Shimadzu» (Japan).
 The electronic absorption spectra of TG and MT have absorption bands in the UV spectral region. It was established experimentally that the excitation spectra of TG and MT are similar to their absorption spectra (λex = 318 nm (TG) and λem = 274 nm (MT)). The effect on the luminescence intensity of TG and MT of methanol, ethanol, acetonitrile, dimethylformamide, dimethylsulfoxide, propanol (50 v/v) was studied. It is established that the maximum luminescence is observed in water.
 The methods were validated according to the following parameters: specificity, linearity, accuracy, limit of quantitation. The degree of extraction of trazodone hydrochloride and melatonin from applicators and surfaces of pharmaceutical equipment is more than 90%. The developed methods can be recommended for determining the residual amounts of trazodone hydrochloride and melatonin while monitoring the quality of the cleaning of pharmaceutical equipment.

Determination of the glucose residues on pharmaceutical equipment surfaces by both methods: polarimetry and HPLC

Cleaning of equipment in the production of medicines is an important requirement of good manufacturing practice (GMP). As a rule, the same process equipment is used for the production of a number of different drugs that may result in cross-contamination. In order to prevent the contamination there is need in efficient cleaning of equipment used with the validation methods for each part of equipment. There is need as well to prove and establish acceptable residual limits of active pharmaceutical ingredients (API) on the surface of the equipment after purification (purity acceptance criteria) based on the therapeutic dose of API, toxicity, volume of series, the surface area of the used equipment.
 The aim of this work is the development of the simple and selective polarimetry and HPLC methods for determining residual amounts of glucose in washings from surfaces of pharmaceutical equipment after production of the drug. The object of the research is glucose, which is a part of the drug Regidron, powder for oral solution of 18.9 g per sachet. The swab Alpha® Sampling Swab TX715; membrane filters 0.20 µm; Minisart RC 15 «Sartorius» (Germany) were used. The polarimetric and HPLC methods for determination of glucose residues in washings from surfaces of pharmaceutical equipment after production the Regidron were developed.
 The recovery rates of glucose from swabs and pharmaceutical equipment surfaces are more than 90%. The proposed simple and rapid methods are characterized by satisfactory metrological characteristics and can be recommended to determine the residues of glucose in controlling the quality of cleaning pharmaceutical equipment.

Determination of residual amounts of Rosuvastatin Calcium on the surfaces of pharmaceutical equipment by HPLC and luminescence

Highly sensitive procedures are proposed for the chromatographic (high-performance liquid chromatography, HPLC) and luminescence determination of trace amounts of Rosuvastatin Calcium in washings after the cleanup of pharmaceutical equipment. The developed procedures are validated for the following parameters: specificity, linearity, accuracy, detection limit, and quantification limit. The calibration curves are presented in the concentration range 0.01–1.0 µg/mL (HPLC) and 0.1–10.0 µg/mL (luminescence); the detection limits are 0.005 and 0.032 µg/mL, respectively. The efficiency of the sampling method is over 90%. It is found that the difference in the results of analysis of samples by two procedures is statistically insignificant. The luminescence procedure compared to HPLC has several advantages, i.e., lesser labor intensity, rapidity, and lesser reagent consumption; but the HPLC procedure is an order of magnitude more sensitive.

LUMINESCENCE DETERMINATION OF ETODOLAC

A highly sensitive, simple and rapid method for determination of non-steroidal anti- inflammatory drug – etodolac (Et) in washings from surfaces of pharmaceutical equipment have been proposed. The intensity of native luminescence of water-n-propanol solutions of etodolac (λex= 274 nm; λlum= 350 nm) was used as the analytical signal. The calibration graph is linear in the concentration range 0.014-2.3 μg/ml, the limit of detection is 0.5 ng/ml.

Development and validation of cleaning procedure of mixing equipment used for manufacturing ceftriaxone and Sulbactam injection tablet by using total organic carbon

–This paper presents a useful method using total organic carbon analyzers employing combustion for validating equipment cleaning procedures and verifying cleaning in a pharmaceutical plant. The study summarizes the initial steps that should be taken into account and focuses particularly on the solutions to some of the most critical considerations (e.g., detection and quantification limits, recovery). Also described are the calculation limits and the good results obtained. Cleaning validation is the process of assuring that cleaning procedures effectively remove the residue from manufacturing equipment/facilities below a predetermined level. This is necessary to assure the quality of future products using the equipment, to prevent cross-contamination, and as a World Health Organization Good Manufacturing Practices requirement. We have applied the Total Organic Carbon (TOC) analysis method to a number of pharmaceutical products. In this article we discuss the TOC method that we developed for measuring residual of sulbactam and ceftriaxone injection contain sulbactam (500mg) and ceftriaxone (1000mg) on surface of mixing tank during manufacturing process. Sulbactam contain 37.61%carbon and ceftriaxone contain 32.64% carbon The method with correlation coefficient R2 = 0.998 and method offers low detection capability (0.01ppm) and rapid sample analysis time. The accurate recovery values ranged from 96.46±1.92 with method precision less than 2%RSD of precision. We found that the TOC method is applicable for determining residual of sulbactam and ceftriaxone on pharmaceutical equipment surfaces and will be useful for cleaning validation. Keywords––Ceftriaxone, equipment surface (mixing tank), injection, sulbactam, Total Organic Carbon

Development and Validation of a High-Performance Thin-Layer Chromatographic Method for Determination of Ofloxacin Residues on Pharmaceutical Equipment Surfaces

An HPTLC method with densitometric quantification using fluorescence at 313 nm was developed and validated for the determination of ofloxacin residue in controlling pharmaceutical equipment cleanliness. Simulated samples at a residue level of 1 mg/m2 were prepared by spreading the calculated amount of ofloxacin solution on 1, 5, and 10 dm2 stainless steel surfaces. After evaporation of the solvent, the residue was removed by two ethanol wetted cotton swabs, which were thereafter extracted with the mixture of ethanol and Na2EDTA-water solution at pH 11 for 15 min with sonication. The extract and standards were applied on HPTLC silica gel 60 plates and then developed in a horizontal developing chamber from both sides using ethanol-conc. ammonia (4+1, v/v) as the mobile phase. The mean recovery (n=6) at 1 mg/m2 from 1, 5, and 10 dm2 was 95.3, 88.6, and 89.7% with the CV values 3.78, 4.41, and 4.97%, respectively. The absolute detection limit was 0.6 ng and the quantitation limit was 2 ng, but it was shown that these can be improved by immersion of the developed plate into a solution of liquid paraffin-n-hexane (1+2, v/v) to approximately 0.25 and 0.9 ng, respectively. The LOD of the method using detection without paraffin-n-hexane was 3, 0.6, and 0.3 microg/m2 by swabbing 1, 5, and 10 dm2, respectively. The method can be applied to routine control of pharmaceutical equipment cleanliness by sampling from stainless steel surface areas of 1 to 10 dm2 with acceptable residue limit/surface of 1 mg/m2.

TLC Determination of Mebendazol and Pentoxifylline as Residues on Pharmaceutical Equipment Surfaces

This paper presents the applicability of thin-layer chromatographic methods with a subsequent densitometric or video densitometric quantitation for determination of residues in controlling pharmaceutical equipment cleanliness. Analytical methods were developed for monitoring residues of pentoxifylline at 10 mg/M2 and mebendazol at 1 mg/M2 on stainless steel surfaces. Simulated samples were prepared by addition of a calculated amount of pharmaceutical (as a solution) on a 35 x 35 cm stainless steel surface. After evaporation of solvent, the residues were wiped with wetted cotton. The cotton was extracted with dichloromethan-methanol (1 + 1). Filtered extract was concentrated by vacuum evaporation and an aliquot applied to the plate, where standards were also applied. In the narrow concentration range near the acceptable residue limits, linear calibration curve could be obtained for both substances. The mean recovery (n = 4) obtained by densitometric quantitation was 93.4% for pentoxifylline and 85.6% for mebendazol, with coefficients of variation of 3.5 and 8.3%, respectively. Results of video densitometric quantitation did not differ significantly. However, data acquisition and evaluation is faster compared with densitometry and allows better archiving possibilities as required by the regulatory authorities. Both quantitation modes can be applied to routine control of pharmaceutical equipment cleanliness.

High-performance thin-layer chromatography method for monitoring norfloxacin residues on pharmaceutical equipment surfaces

This paper presents a high-performance thin-layer chromatography (HPTLC) method with direct fluorescence measurement for the determination of norfloxacin. The method was validated for the monitoring of norfloxacin residues on stainless steel surfaces at the allowed limit of 10 mg of norfloxacin per square meter. However, it can be adapted for lower amounts of residues owing to the low detection limit of norfloxacin (about 5 ng) and can also be used for other surface materials. Test solutions were analyzed by the new HPTLC method and the known HPLC method for comparison. Accuracy and precision of the new HPTLC method, with a subsequent quantification by densitometer or video system, are comparable with those of the HPLC method.