Manufacturing Equipment Surfaces Research Articles

Multi-length Scale Approach to Investigate Cleaning of Food-Derived Deposits Adhered to Hard Surfaces: Mixtures of Starch, Whey Protein, and Lard

AbstractFouling, the accumulation of undesirable material on manufacturing equipment surfaces, poses a pervasive challenge in industrial processes. In the food industry, the complex interactions among these compounds can give rise to stubborn deposits that deviate from conventional cleaning protocols. In this work, the forces and removal mechanisms of model fouling agents composed of mixtures of starch, whey protein, and lard deposited on solid surfaces of relevant industrial interest (i.e. stainless steel, aluminium, and PTFE) are investigated using a multi-length scale approach, involving milli-manipulation and a lab-simulated Clean-In-Place (CIP) system. The forces involved in the removal process, the types of failure observed when the deposits are subjected to shear stress (adhesive, mixed, or cohesive), and the performance of the CIP system are systematically analysed as a function of the cleaning treatments applied. For stainless steel surfaces, alkaline treatment seems to facilitate the cleaning of lard and starch deposits, while the whey foulant removal tends to be more effective using hot water under the conditions tested. Hot water is effective for stainless steel and PTFE surfaces, reducing the mechanical shear stress required, while the alkaline treatment demonstrated superior efficacy for aluminium surfaces. These findings emphasise the importance of customising cleaning protocols for CIP optimisation.

Determination of betamethasone residues on manufacturing equipment surfaces and PDE calculation in cleaning validation processes

Determination of betamethasone residues on manufacturing equipment surfaces and PDE calculation in cleaning validation processes

Sensitive determination of naftazone using carbon quantum dots nanoprobe by fluorimetry and smartphone-based techniques

A simple, fast, and direct mix-and-read spectrofluorimetric method has been developed for the sensitive determination of naftazone (NFZ) utilizing graphene quantum dots (GQDs) as a greener and highly luminescent nanosensor. NFZ effectively quenches the strong fluorescence of GQDs at λex/λem of 350/440 nm via the inner filter effect mechanism. The nanosensor exhibits excellent linearity for NFZ over the concentration range of 0.46 to 186 μM with a limit of detection of 0.04 μM. The proposed method was validated for the successful determination of NFZ in tablets and on manufacturing equipment surfaces with good % recoveries of 98.4–101.6 and 96.3 – 102.2%, respectively. Furthermore, an integrated smartphone-based reader has been implemented and successfully applied for the determination of NFZ. The smartphone-based reader consists of a 365 nm UV torch as an excitation source, a smartphone for recording images, and smartphone-powered image analysis software for signal interpretation, together with a paper-based analytical device (PAD) utilizing filter paper as a substrate and correction fluid as a barrier for creation of detection zones. This smart platform showed excellent sensitivity with a limit of detection down to 0.12 nmol/zone, and it could be used for in-site determination of NFZ, especially for the limited resources laboratories.

Sustainable and smart HPTLC determination of silodosin and solifenacin using a constructed two illumination source chamber with a smartphone camera as a detector: Comparative study with conventional densitometric scanner

The tremendous revolution in the built-in digital camera of smartphones has opened new horizons for its applicability as a portable, easily accessible, and user-friendly detector in different analytical techniques. In this article, we proposed and developed a new and inexpensive detector for simultaneous analysis of silodosin and solifenacin. The innovation makes use of a smartphone camera coupled with high-performance thin layer chromatographic (HPTLC) approach. Firstly, chromatographic separation was attained using HPTLC plates with an ecofriendly mobile phase composed of ethyl acetate, ethanol & 25% w/w ammonia (3.0: 7.0: 0.3, by volume). The developed plates were then visualized using Dragendorff's reagent and then photographed via smartphone's rear-facing camera fixed on a fabricated two-illumination source chamber. The intensities of drug spots were quantified using an open-source image analysis software, ImageJ, over concentration ranges of 2.0–30.0 μg/band. Moreover, the study was extended to compare the obtained results with a benchtop densitometric method at 215.0 nm where the densitometric one gave linear response ranging from 0.1 to 7.0 μg/band for silodosin and 0.1–6.0 μg/band for solifenacin. The fast, simple, reliable and green merits of the proposed HPTLC/smartphone method promted it as an excellent platform for assaying marketed combined tablets and assuring their content uniformity. Moreover, the high sensitivity of the densitometric method was exploited, for the first time, for determining the residual content of the cited drugs on manufacturing equipment surfaces during cleaning validation. Finally, the environmental impact of the methods was appraised via three state-of-the-art greenness metrics.

A novel smartphone HPTLC assaying platform versus traditional densitometric method for simultaneous quantification of alfuzosin and solifenacin in their dosage forms as well as monitoring content uniformity and drug residues on the manufacturing equipment.

The large popularity and rapid technology of smartphones have opened new avenues for their integration into different analytical methodologies and drug quality monitoring as a portable, easily accessible, and user-friendly detector. Herein, a novel and portable smartphone-based high-performance thin layer chromatographic (HPTLC) approach is proposed for the simultaneous analysis of two urological drugs, alfuzosin and solifenacin, which treat benign prostatic hyperplasia accompanied by overactive bladder syndrome. First, chromatographic separation was accomplished using an ecofriendly mobile phase, then the developed plates were visualized using Dragendorff's reagent and photographed via a smartphone's rear-facing camera fixed on a fabricated two-illumination-source chamber. The intensities of the drug spots were quantified using open-source image analysis software ImageJ over the concentration ranges of 2.0 to 30.0 μg per band for both drugs with acceptable results in ICH validation parameters. To improve the method's accuracy and reproducibility, various construction and shooting key parameters were investigated and optimized. Moreover, the study was extended to compare the obtained results with those of a benchtop densitometric method using a Camag TLC Scanner 3 at 215.0 nm; the densitometric method provided an additional assessment tool for peak purity and was capable of assaying lower drug concentrations over a linearity range of 0.2-8.0 μg per band for alfuzosin and 0.1-6.0 μg per band for solifenacin. The fast, simple, reliable, green merits of the proposed HPTLC/smartphone method suggest that it is an excellent platform for assaying marketed combined capsules and assuring their content uniformity. Moreover, the high sensitivity of the densitometric method was used, for the first time, to determine the residual content of the cited drugs on manufacturing equipment surfaces for cleaning validation. Finally, the environmental impact of the developed methods was evaluated based on green analytical chemistry principles.

Determination of loratadine residues from manufacturing equipment surfaces and setting acceptance limits for cleaning validation

Determination of loratadine residues from manufacturing equipment surfaces and setting acceptance limits for cleaning validation

Сloud point extraction coupled with HPLC-UV for the determination of ibuprofen residues on stainless steel surface of pharmaceutical manufacturing equipment

A new application of cloud point extraction coupled with HPLC-UV was developed for the determination of ibuprofen residues on stainless steel surface of pharmaceutical manufacturing equipment. Some parameters with an effect on the cloud point extraction of ibuprofen, such as the concentration of Triton X-114, pH influence, incubation time, equilibration temperature, and centrifuging parameters, were studied and optimized. For optimal cloud point extraction solution of Triton X-114 with concentration 0.3% (w/v) and pH= 3.0 was selected. Wipes soaked with 0.001 M sodium carbonate solution were used to remove ibuprofen residues from stainless steel surfaces. The method was validated over a concentration range of 10–100 ng mL−1. The LOD and LOQ for ibuprofen were found to be 14 and 46 ng mL−1, respectively. Recoveries were 108.9%, 105.6%, and 104.9% with RSD ranging from 4.0% to 10.0% at three concentration levels.

Spectroscopic method for the quantification of residue of Tetramethylthionine chloride on swab from manufacturing equipment in support of cleaning validation

Tetramethylthionine chloride is approved by the FDA for the treatment of paediatric and adult patients with acquired methaemoglobinaemia. The objective of this research was to develop and validate an Ultraviolet (UV) spectrophotometric method for quantification of Tetramethylthionine chloride in cleaning control swab sample from manufacturing equipment surfaces. Simple, accurate and cost efficient spectrophotometric method has been developed for the estimation and quantification of Tetramethylthionine chloride which is going to be used for the evaluation of cleaning in cleaning validation. The optimum conditions for the quantitative analysis of the drugs were established. The maximum wavelength (λmax) was found to be 663nm. The percent recovery of Tetramethylthionine chloride for 50.0%, 100.0% and 150.0% were 99.13, 97.76 and 101.18 respectively. Linearity of Tetramethylthionine chloride for Validation showed a good linear relationship with Correlation Coefficient (r2) value of 0.999 was obtained. Validation was performed according to the ICH guidelines of Analytical Method Validation. The Sample Solution was chemically stable up to 36 hours. The proposed may be suitable for the Estimation and Quantification of Tetramethylthionine chloride for evaluation of cleaning in cleaning validation for quality control purposes.

QUANTITATIVE DETERMINATION OF TERBINAFINE RESIDUES ON THE PHARMACEUTICAL MANUFACTURING EQUIPMENT SURFACES

Background: Cleaning validation is a critical analytical responsibility required by GMP (Good Manufacturing Practice), which confirms the effectiveness of the cleaning standard procedure in the pharmaceutical manufacturing process for all the produced drug products contacting the shared pharmaceutical manufacturing equipment. The need to carry out cleaning validation is especially important when the drug product is the “worst-case” for the cleaning procedure regarding solubility, therapeutic potency, toxicity, and surface adherence of active pharmaceutical ingredients (API). Estimation of API residues requires a selective and sensitive method capable of quantitative determination of API traces remaining over the surface of manufacturing equipment after the cleaning procedure. Aim: The present study demonstrates the suitability and the applicability of the proposed method obtained with a combination of a sensitive, selective, and specific analytical HPLC and effective swab wipe sampling procedures for quantitative estimation of terbinafine residues in samples collected from pharmaceutical manufacturing equipment surfaces and the efficiency of the developed standard procedure for cleaning of the shared manufacturing equipment in support of cleaning validation. Methods: The swab sampling procedure was developed to obtain a suitable recovery (>80 %). The surface (sampling area – 25 cm2) was wiped with one swab moistened with methanol. The analytical procedure was developed using the HPLC system “Agilent 1260 Infinity II” and BDS Hypersil C18 250×4.6 mm, 5 ?m column with an isocratic elution of mobile phase. Results and Discussion: The developed combined method was validated concerning chromatographic system suitability test, specificity, linearity range, accuracy, precision, the limit of detection (LOD), and quantitation (LOQ). The stability of terbinafine HCl solutions in methanol, the swab material, and membrane filter compatibility was also studied. The calibration curve was linear (R2=0.99999) over a concentration range 0.00003-0.025 mg/mL; LOD – 0.000015 mg/mL, and LOQ – 0.00003 mg/mL; The determined concentrations of terbinafine residues in test solutions were not more than 0.00090 mg/mL which are below the limit of cross-contamination of the next drug product. Conclusions: The performed analytical study using the developed method with a combination of an analytical HPLC and swab sampling procedures for estimation of terbinafine residues on surfaces of the pharmaceutical equipment used during the manufacture of Terbinafine HCl 250 mg uncoated tablets demonstrates the validity of the cleaning procedure. Other quality control laboratories can apply the proposed method to carry out cleaning validation on various drug formulations of terbinafine HCl.

Development and Validation of Analytical Test Method for the Determination of Oseltamivir Phosphate Residues on the Manufacturing Equipment Surfaces Equipment Using Swab and Rinse Sampling and by High Performance Liquid Chromatographic Technique

Development and Validation of Analytical Test Method for the Determination of Oseltamivir Phosphate Residues on the Manufacturing Equipment Surfaces Equipment Using Swab and Rinse Sampling and by High Performance Liquid Chromatographic Technique

Correction pen as a hydrophobic/lipophobic barrier plotter integrated with paper-based chips and a mini UV-torch to implement all-in-one device for determination of carbazochrome

The design of a cheap, simple, and handy sensing system for rapid quantitation of pharmaceuticals becomes mandatory to ease drug development procedures, quality control, health care, etc. This work describes a simple, innovative, and easily manufactured paper-based device using a correction pen as a plotter for hydrophobic/lipophobic barriers and graphene quantum dots for recognition and quantification of the hemostatic drug carbazochrome, via fluorescence turn-off mechanism mediated by the inner filter effect. A smartphone-based all-in-one device fitted with an inexpensive 365 nm flashlight as a UV light source and a free image processing software was developed for rapid and reliable interpretation of the fluorescence change from the paper-based device upon introduction of the drug. The simple and convenient steps permit the analysis of many samples in a very short time. The smartphone-based all-in-one device featured excellent sensitivity for carbazochrome with a limit of detection equals to 12 ng/detection zone and good %recovery (100.0 ± 0.4). The reliability of the device was ascertained by favorable statistical comparison with the analogous optimized conventional fluorimetry method and a reference HPLC method. The device has been successfully applied for versatile quantitation of carbazochrome in tablets and on manufacturing equipment surfaces with excellent recoveries. The device offers many green aspects that definitely assist the implementation of the sustainability concept to analytical laboratories. The cost-efficiency, reliability, and ease of fabrication as well as the greenness and user friendship qualify the device for wide application in low-income communities.

Simultaneous Quantitative Estimation of Lisinopril and Hydrochlorothiazide Residues Using HPLC for Cleaning Validation

(PDF) Graphical Abstract: A new, rapid and selective, HPLC method for simultaneous quantitative estimation of lisinopril and hydrochlorothiazide residues and sampling procedures from pharmaceutical manufacturing equipment surfaces were developed and validated. The sampling procedures have a good recovery (>80%). The limit of quantitation of the HPLC method - 0.155 µg/mL and 0.025 µg/mL for lisinopril and hydrochlorothiazide, respectively.

Cleaning Validation for Residual Estimation of Mometasone Furoate on Stainless-Steel Surface of Pharmaceutical Manufacturing Equipment Using a UHPLC-UV Method.

Cleaning validation is the documented evidence that shows the effectiveness of cleaning procedures for the removal of product residues and other contaminants. The cleaning procedures must be validated and methods to determine trace amounts of drugs have to be considered with special attention. An ultra-high-performance liquid chromatography-ultraviolet (UHPLC-UV) method for the determination of mometasone furoate residues on stainless-steel surfaces was developed and validated in order to control a cleaning procedure. The chromatography separation was achieved on a Waters Acquity UPLC HSS T3 column (50 × 2.1 mm, 1.8 µm) at 40°C using acetonitrile and water (1:1, v/v) as the mobile phase at a flow rate of 0.5 mL/min. The injection volume was 2 µL, and the detection was performed at 254 nm. The swab and rinse procedures were optimized in order to obtain a recovery higher than 90% of mometasone furoate from stainless-steel surfaces, using ethanol as the extraction solvent. The method was validated in the range of 0.2-2.6 µg/mL and showed appropriate selectivity, limit of detection and quantification, linearity, precision, accuracy, and robustness. This method was found to be simple, fast, and sensitive for determination of mometasone furoate residues and, therefore, can be used for cleaning validation analysis.

Cleaning method validation for estimation of dipyridamole residue on surface of the drug product manufacturing equipment using the swab sampling and by using high performance liquid chromatographic technique

Cleaning method validation for estimation of dipyridamole residue on surface of the drug product manufacturing equipment using the swab sampling and by using high performance liquid chromatographic technique

Computational approaches to predict the effect of shear during processing of lubricated pharmaceutical blends

In the production of pharmaceutical tablets and capsules, a lubricant such as magnesium stearate is often added to the powder blend or granulation in order to reduce friction and, in some cases, minimize sticking to the manufacturing equipment surfaces. If the lubricated blend is exposed to excessive shear during the processing steps prior to tableting or encapsulation, adverse effects on quality attributes of the final dosage form may be observed. These could include an increase in wetting contact angle, a slowdown in disintegration and/or dissolution, and a reduction in the tensile strength of compacts. In this work, two different computational modeling approaches are proposed to predict the effect of shear during the processing of lubricated pharmaceutical blends on drug product quality attributes. In this case study, an agitated powder feed system is examined, but the approach could be readily extended to other powder processing operations. First, a framework for the prediction of lubrication-based tensile strength reduction using the discrete element method (DEM) is proposed. This approach utilizes a companion study in a lab-scale, high-shear mixer to map the DEM predictions of extent of shear to an experimentally relevant tensile strength prediction. Second, a compartment model (CM) approach is proposed to model the powder flow and lubrication in the feed system. The tensile strength predictions from these two different approaches both compare favorably to experimental measurements of tensile strength.

Determination of Fenspiride Hydrochloride Residues on Pharmaceutical Manufacturing Equipment Surfaces by HPLC Method

The cleaning procedure must be validated, so special attention must be devoted to the methods used for determination of trace amounts of drugs. A rapid, sensitive, and specific reverse phase high-performance liquid chromatographic (HPLC) method was developed for the quantitative determination of fenspiride hydrochloride residues on pharmaceutical manufacturing equipment surfaces. The calibration curve was linear over a concentration range from 1.0 to 100.0 μg/ml with a correlation coefficient of 0.99994. The detection limit and quantitation limit were 0.41 μg/ml and 1.25 μg/ml, respectively. The developed method was validated with respect to specificity, linearity, limit of detection, accuracy and precision.

Development of a Cleaning Validation Protocol for an Odd Case Scenario and Determination of Methoprene residues in a Pharmaceutical Manufacturing Equipment Surfaces by using a Validated UFLC Method

In veterinary pharmaceutical industries, it is very important to remove drug residues from the equipment and areas used for the manufacturing of a product. At the same, the associated cleaning procedures must be validated. In the present report, initially a protocol was developed to determine the Maximum Allowable Carryover (MAC) of methoprene based on an odd case scenario. A rapid, sensitive and specific reverse phase ultra-fast liquid chromatographic (UFLC) method was developed and validated for the quantitative determination of methoprene in cleaning validation swab samples. According to developed protocol, the MAC was found to be 1.068 µg/cm2. Cotton swabs, moisten with extraction solution (100% methanol) were used to remove any residue of drug from stainless steel, glass and silica surfaces and give recoveries >80% at three concentration levels. The precision of the results, reported as the relative standard deviation, were below 2.5%. The calibration curve was linear over a concentration range from 0.15625 to 5.0 µg/ml with a correlation coefficient of 1. The method was validated over a concentration range of 0.15625–5.0 µg/ml. The developed method was validated with respect to specificity, linearity, accuracy, precision, and robustness.

Validation of Swab Sampling and HPLC Methods for Determination of Meloxacam Residues on Pharmaceutical Manufacturing Equipment Surfaces for Cleaning Validation

The swab sampling and HPLC methods for residual estimation of meloxicam in swab samples from equipment surfaces after manufacturing of Mobicam 15 mg (meloxicam 15 mg) uncoated tablets were developed and validated. The swab sampling method was developed and optimized in order to obtain a suitable recovery (>90 %). Polyester swabs were moistened with diluent a mixture of methanol, 1 M sodium hydroxide solution and water 28:2:20. The HPLC method was developed using Luna C18(2) 150 × 4.6 mm, 5 μm column with a mobile phase a mixture of solution A and solution B (63 : 37); The flow rate – 0.8 ml/min; The column temperature 40°C; The detector wavelength 254 nm; The injection volume – 25 μl. The calibration curve is linear (the r=1.00000) over a concentration range 0.11μg/ml – 88 μg/ml; The limit of detection and the limit of quantitation are 0.11μg/mL and 0.014 μg/ml, respectively; No interference from swab solution was observed and samples were stable for 24 h. The determined concentration varying 0.016 – 5.8 μg/ml are well below the calculated limit of contamination. So the proposed validated HPLC method with appropriate swab wipe procedure could be applicable for cleaning validation on residues of meloxicam.

Development and Validation of method of analysis of drug residue on manufacturing equipment surfaces.

Development and Validation of method of analysis of drug residue on manufacturing equipment surfaces.

Determination of residues of acetaminophen, caffeine, and drotaverine hydrochloride on swabs collected from pharmaceutical manufacturing equipment using HPLC in support of cleaning validation.

An HPLC method was developed for the simultaneous determination of residues of acetaminophen (paracetamol, PA), caffeine (CA), and drotaverine HCl (DH) on swabs collected from pharmaceutical manufacturing equipment surfaces. The challenge in cleaning validation is to develop analytical methods that are sensitive enough to detect traces of the active compounds remaining on the surface of pharmaceutical manufacturing equipment after cleaning. Chromatography was performed in the isocratic mode on a Hypersil C18 BDS column using the mobile phase 0.02 M tetrabutylammonium bisulfate-methanol (100 + 45, v/v) at 50°C with UV detection at 210 nm. The method was tested for specificity, linearity, LOD, LOQ, accuracy, and precision for determination of traces of the above-mentioned drugs. The time required for a single analysis was 12 min. The response was linear in the ranges of 6.900-52.100, 1.040-7.800, and 0.694-5.210 μg/mL for PA, CA, and DH, respectively.