Quality Control Of Pharmaceutical Products Research Articles

Development of a sustainable procedure for smartphone-based colorimetric determination of benzalkonium chloride in pharmaceutical preparations

A sustainable procedure offering green, simple, and rapid analysis was developed to determine benzalkonium chloride (BKC) in pharmaceutical preparations. The determination using smartphones was based on the ion pair colorimetric reaction with bromothymol blue (BTB), which produces a yellow color. The intensity of the product color, which is proportional to the concentration of BKC, was detected and evaluated using a smartphone camera and an image processing application. The procedure was performed in a microliter and was rapidly detected within 1 min after incubation. This offered high throughput at 28 samples per well plate in duplicate. Linear calibration, which was a plot of BKC concentrations and relative red intensities, was in the range of 2.0–24.0 μg/mL with an R2 of 0.997. The limits of detection (LOD) and quantitation (LOQ) were 1.0 and 3.2 μg/mL, respectively. This work was successful in applying it to pharmaceutical materials, disinfectant products, and pharmaceutical products containing BKC. It was discovered that the concentrations of BKC as an active ingredient in pharmaceutical materials were 82% w/v, whereas those in disinfectant products ranged from 0.4 to 2.1% w/v. In pharmaceutical products, ophthalmic drops and nasal sprays contain BKC as preservatives in the 0.01–0.02, and the 0.02% w/v, respectively. The results obtained by the proposed procedure compared with a reference titration method showed no significant differences at a 95% confidence level with 1.2–3.4% RSDs. This promotes the efficiency of pharmaceutical preparations regarding infection prevention and control by ensuring that available disinfectants contain a sufficient concentration of BKC. Additionally, this improves the efficiency of pharmaceutical preparations for quality control of pharmaceutical products by ensuring that the available preservatives maintain a sufficient concentration throughout the lifespan of the products.

An aptamer-based SERS method for rapid screening and identification of pathogens assisted by machine learning technique with robustness evaluation

Pathogen testing is one of the compulsory items for the quality control of pharmaceutical products. Up to now, rapid screening and identification of low-concentration pathogen contaminations is still full of challenge. Herein, an aptamer-coated magnetic beads (Apt-MBs)-based isolation strategy combined with culture medium turbidity observing and label-free SERS detection technique has been developed for rapid screening and detection of Escherichia coli, Salmonella Typhimurium and Staphylococcus aureus. Apt-MBs were employed for capturing and isolation of target pathogens. Then, with a simple enrichment process, the potential pathogens could be screened out by observing the turbidity of liquid culture medium. The presumptive bacteria species was furtherly identified via a silicon-based SERS chip couple with an optimized machine learning model, which was selected by directly evaluating the model’s generalization ability on test data. The results demonstrated that SoftMax classifier had the optimal performance with the recognition accuracy of 100 % for all samples. Finally, the method was successfully applied for identification of pathogens at ∼1 CFU spiked level in drug samples within 24 h, which is much shorter than that of the standard culture-based method (3–5 d). Therefore, the developed method showed a promising application in monitoring pathogen levels in pharmaceutical industries.

Comparing the Performance of Raman and Near-Infrared Imaging in the Prediction of the In Vitro Dissolution Profile of Extended-Release Tablets Based on Artificial Neural Networks.

In this work, the performance of two fast chemical imaging techniques, Raman and near-infrared (NIR) imaging is compared by utilizing these methods to predict the rate of drug release from sustained-release tablets. Sustained release is provided by adding hydroxypropyl methylcellulose (HPMC), as its concentration and particle size determine the dissolution rate of the drug. The chemical images were processed using classical least squares; afterwards, a convolutional neural network was applied to extract information regarding the particle size of HPMC. The chemical images were reduced to an average HPMC concentration and a predicted particle size value; these were used as inputs in an artificial neural network with a single hidden layer to predict the dissolution profile of the tablets. Both NIR and Raman imaging yielded accurate predictions. As the instrumentation of NIR imaging allows faster measurements than Raman imaging, this technique is a better candidate for implementing a real-time technique. The introduction of chemical imaging in the routine quality control of pharmaceutical products would profoundly change quality assurance in the pharmaceutical industry.

Comparison of several strategies for the deployment of a multivariate regression model on several handheld NIR instruments. Application to the quality control of medicines

Chemometrics applied to spectroscopic measurements such as near-infrared are gaining more and more importance for quality control of pharmaceutical products. Handheld near-infrared devices show great promise as a medicines quality screening technique for post-marketing surveillance. These devices are able to detect substandard and falsified medicines in pharmaceutical supply chains and enable rapid action before these medicines reach patients. The instrumental and environmental changes, expected or not, can adversely affect the analytical performances of prediction models developed for routine applications. Based on a previous study, PLS prediction models were developed and validated on three similar handheld NIR transmission spectrophotometers of the same model and from same company. These models have shown to be effective in analyzing metformin tablet samples, but significant spectral differences between handheld systems complicated their deployment for routine analysis. In this study, different strategies have been applied and compared to correct the instrumental variations, including global modelling (GM) and calibration transfer methods (Direct Standardization, DS; Spectral Space Transformation, SST and Slope/Bias correction, SBC), considering the RMSEP and the accuracy profile as assessment criteria. The transfer methods showed good capabilities to maintain the predictive performances comparable to that of the global modelling approach, except for a remaining slight bias. This approach is interesting since very few standardization samples are required to develop an adequate transfer model. GM, SST and SBC were able to correct/handle drifts in the spectral responses of different handheld instruments and thus may help to avoid the need for a long, laborious, and costly full recalibration process due to inter-instrument variations.

Rapid Determination of Arsenic in Traditional Chinese Medicine by Laser-Induced Breakdown Spectroscopy (LIBS)

High arsenic (As) content in medicine may threaten health and its determination is necessary. However, traditional methods cannot achieve rapid analysis because of complex digestion procedures. Exploring rapid and accurate methods for the determination of As is urgent. In this study, the As concentration in niuhuangjiedu tablets (NHJDTs) was accurately and rapidly determined by laser-induced breakdown spectroscopy (LIBS). Furthermore, comprehensive health risks of As were analyzed combined with solubility measurements to evaluate the impact on humans. The results showed that the relative standard deviation and relative error of the LIBS results were less than 10% for detection period of less than 0.3 h, which meets the requirements for rapid, accurate, and convenient As determination. The indices for non-carcinogenic and carcinogenic risk for total As and soluble As in niuhuangjiedu tablets were 966.67, 0.15, 4.37, and 6.72 × 10−4, respectively, indicating the presence of potential health risks. This work provided support for further investigation for quality control of pharmaceutical products.

Greenness assessment of micellar spectrofluorometric approach for determination of Elagolix: application to dosage form, content uniformity and human plasma

Ecological, sensitive, fast and economic approaches are the main aspects in quality control of pharmaceutical products. Elagolix (ELG) is an orally non-peptidic GnRH antagonist, recently approved drug by Food and drug administration in 2018 for treatment of pain associated with endometriosis. A green, and sensitive method was developed and validated for determination of ELG based on micellar spectrofluorometric approach. Many factors were studied to enhance the fluorescence intensity of ELG and the highest sensitivity was obtained upon using 1% Sodium dodecyl sulphate (SDS) at 438 nm after excitation at 270 nm. A linear relationship was obtained over a range of 50–1000 ng mL−1 between ELG concentration and corresponding fluorescence intensity. The developed method was validated according to ICH guidelines and successfully applied for testing the content uniformity and determination of ELG in pharmaceutical dosage forms with percentage recovery 99.31 ± 1.98. Furthermore, the capability of the method due to its high sensitivity to determine ELG in human plasma with percentage recoveries in a range of 98.54–100.46. The greenness of the method was investigated using three different approaches; Analytical Procedure Index (GAPI), Analytical Eco-Scale and Analytical Greenness Metric (AGREE).

Fe(III)-mediated reversible catalytic activity of MoS2 nanozymes for bisphosphonate drug sensing

Peroxidase-like activity of MoS2 quantum dots (QDs) can be reversibly regulated by means of Fe3+/alendronate sodium (ALDS)-induced aggregation/disaggregation of the QDs in solution. Specifically, Fe3+ can selectively aggregate the MoS2 QDs and thus greatly enhance their peroxidase-like activity, while such enhancement can be inhibited in the presence of ALDS owing to the competitive coordination of ALDS with Fe3+. By regulating the enzyme-like activity of MoS2 QDs, different colorimetric signal of a typical substrate of horseradish peroxidase, 3,3΄,5,5΄-tetramethylbenzidine, can be measured in the presence of H2O2. Based on this mechanism, we develop a colorimetric approach for the determination of ALDS and further applied in quality control of pharmaceutical products, utilizing either smartphone or UV–vis spectrometer as a readout. This detection method is rapid and selective, where derivatization of ALDS before detection is not needed. Such a smartphone-based colorimetric detection platform is promising to be applied in point-of-care testing at home, small clinics, or underdeveloped regions.

Membrane Distillation for the Production of Pharmaceutical-Grade Water-Investigation into the Application of AGMD and VMD.

The production of pharmaceutical ingredients, intermediates and final products strongly depends on the utilization of water. Water is also required for the purification and preparation of reagents. Each specific application determines the respective water quality. In the European Union, the European Pharmacopeia (Ph. Eur.) contains the official standards that assure quality control of pharmaceutical products during their life cycle. According to this, the production of water for pharmaceutical use is mainly based on multi-stage distillation and membrane processes, especially, reverse osmosis. Membrane distillation (MD) could be an alternative process to these classical methods. It offers advantages in terms of energy demand and a compact apparatus design. In the following study, the preparation of pharmaceutical-grade water from tap water in a one-step process using MD is presented. Special emphasis is placed on the performance of two different module designs and on the selection of optimum process parameters.

Spectrometric Smartphone-Based System for Ibuprofen Quantification in Commercial Dosage Tablets

A rapid and portable analytical methodology has been developed for ibuprofen (IBU) quantification in commercial dosage tablets using a spectrometric smartphone-based system. The analytical methodology employs point-of-use approaches both for sample preparation and detection, demonstrating its potential utility for portable quality control of pharmaceutical products. In this work, IBU is dissolved in methanol and then treated with a Co(II) aqueous solution, forming a blue complex which is extractable by dispersive liquid-liquid microextraction. Then, the sample’s absorption spectrum is directly measured by a spectrometric smartphone-based system using cartridge made of polyoxymethylene for solvent compatibility. The main experimental factors affecting the dispersive liquid-liquid microextraction of Co-IBU complex were optimized using a multivariate analysis. Under optimized conditions, a working range between 20 and 80 μg mL−1 was obtained with a correlation coefficient of 0.996 for 5 calibration points. The limit of detection and limit of quantification obtained were 4 and 12 μg mL−1, respectively. The performance of the proposed methodology was evaluated in commercial tablet dosage forms, and the results demonstrate the ability of the method to determine IBU in samples representative of those used in real-world quality control applications. Recovery values between 97% and 105% were obtained, which are comparable to those obtained via standard titrimetric methodology.

Preferential Orientation Effect of Polymers on Paracetamol Crystallization: Experiments and Modeling

Crystallization is one of the most important unit operations in the quality control of pharmaceutical products. For this study, a polymer-induced heteronucleation method was selected to investigate the effect of nylon 66 (PA66), polyester (PET), and polypropylene (PP) films on the crystal growth of paracetamol by coupling experiments with modeling. The result of induction time indicated that the order of induced effect was PA66 > PET > PP > no template. X-ray photoelectron spectroscopy results indicated the different functional groups on the surface of films. The crystal habits and powder X-ray diffraction results indicated that preferential orientation along certain facets occurred for PA66 and PET, and the results of in situ Raman microscopy verified the different concentration trends near different films, which is consistent with the preferential orientation effect of films. The results of molecular simulation indicated that the difference in van der Waals and electrostatic interaction, as well as H-bo...

International Pharmacy Conference UAD 2017 on Product Authentication: Key Factor in Quality Control of Pharmaceutical Products

Welcome Message from the Conference ChairA product authentication is a process to ensure that a product is authentic or genuine. One of the criteria which becomes the object of authentication is halal products (food, cosmetics and medicine) through the existence of non-halal components of the products.Faculty of Pharmacy, Universitas Ahmad Dahlan has successfully held an International Pharmacy Conference (IPC) with a theme “Product Authentication: Key Factor in Quality Control of Pharmaceutical Product” on 9th September 2017. This event was held as a forum to exchange information between researchers, academics, practitioners and policy holders mainly about halal authentication and regulations in national and international scope. There has been presented many kinds of research article as well.We hope this proceeding can be a usefull knowledge for all readers. We would like to thank to all of the writers, speakers, presenters, participants and committees for the great contribution in this conference.Best regardsDr. Nanik Sulistyani, M.Si., Apt.Conference ChairList of Committee Chairman, Secretary, Treasurer, Scientific, Program, Publication, Editorial Boards are available in this PDF.

ICP-MS: Analytical Method for Identification and Detection of Elemental Impurities.

Aim of this article is to review and discuss the currently used quantitative analytical method ICP-MS, which is used for quality control of pharmaceutical products. ICP-MS technique has several applications such as determination of single elements, multi element analysis in synthetic drugs, heavy metals in environmental water, trace element content of selected fertilizers and dairy manures. ICP-MS is also used for determination of toxic and essential elements in different varieties of food samples and metal pollutant present in the environment. The pharmaceuticals may generate impurities at various stages of development, transportation and storage which make them risky to be administered. Thus, it is essential that these impurities must be detected and quantified. ICP-MS plays an important function in the recognition and revealing of elemental impurities.

An Overview on Novel Microbial Determination Methods in Pharmaceutical and Food Quality Control.

Traditional microbiological methods tend to be labor-intensive and time-consuming. Rapid and novel methods in microbiological tests provide more sensitive, precise and reproducible results compared with conventional methods. In microbiology, the most rapid testing methods belong to the field of biotechnology such as PCR, ELISA, ATP bioluminescence and etc. Nevertheless impedance microbiology, biosensors and analytical procedures to determine microbial constituents are of significance. The present review article was conducted using internet databases and related scientific literatures and articles that provide information on developments in the rapid methods in microbiology. The main focus is on the application of rapid methods in microbial quality control of pharmaceutical products. Reviewed literature showed that rapid methods and automation in microbiology is an advanced area for studying and applying of improved methods in the early detection, and characterization of microorganisms and their products in food, pharmaceutical and cosmetic industrials as well as environmental monitoring and clinical applications. It can be concluded that rapid methods and automation in microbiology should continue as potent and efficient technologies to develop the novel tests to be performed in the future because of the ever-increasing concerns about the safety of food and pharmaceutical products. However the main issues to be considered are the scale up of developed methods and the regulatory requirements.

In-process and Finished Products Quality Control Tests for Pharmaceutical Capsules According to Pharmacopoeias

The quality of pharmaceutical products is essential to assure the maximum level of patient’s satisfaction. The most important criteria for quality of any drug in dosage form are its safety, potency, efficacy, stability, patient acceptability and regulatory compliance. Different parameters of quality control of pharmaceutical products can ensure the quality, bioavailability and optimal therapeutic activity. The maintenance of quality with continuous improvement in facilities is very important in pharmaceutical industries because it is directly related to healthcare system. The quality of a pharmaceutical capsule needs to be designed from the product development stage. In-process quality control (IPQC) tests are done with a view to remove error from every stage in production and maintain the quality of the final product with the compendial standards as specified in the pharmacopoeias. The quality of final products depends on in-process control (IPC) tests, because it helps to incorporate excellence within the products. The qualitative and quantitative parameters of pharmaceuticals products are checked by finished product quality controls (FPQC) tests. The purpose of this study is to provide concise information on the in-process and finished products quality control tests for pharmaceutical capsules as per different pharmacopoeias.

The application of ecologically acceptable concept in liquid chromatographic method development in drug analyses

Liquid chromatography is the most widely used analytical technique in course of research and development, as well as for routine investigation and quality control of pharmaceutical products. Having in mind the remarkable amount of waist resulting from the use of organic solvents, especially for reversed-phase liquid chromatography, recently ecologically acceptable concepts in chromatographic method development were noticed. The 3 Rrule (Reduce - Replace - Recycle) refers to the decrease of the toxic solvents use, their replacement with less toxic ones and the use of renewable solvents. This paper presents different solutions commonly applied in drug analysis that are in accordance with the 3 Rrule.

Review on Application of Nucleic Acid Amplification Techniques in Pharmaceutical Products Analysis

The aim of this study was to describe application of molecular diagnostic tests based on nucleic acid amplification technologies (NAATs) in pharmaceutical product analysis. NAAT have become widely established in clinical microbiology laboratories in recent years, as well as in quality control (QC) laboratories for food testing, and lately introduced to the pharmaceutical QC laboratories. The number of available nucleic acid and gene amplification-based rapid microbiological methods has increased over the last few years, and for good reason. When compare to standard culture based methods, NAAT provide a rapid, an accurate and reliable means for detecting specific microorganisms of interest, especially in pharmaceutical dosage forms that are required to be free of objectionable or specified pharmacopeial organisms. This article discussed about the different types of nucleic acid amplification techniques and methods available to pharmaceutical microbiologists working on quality control of pharmaceutical products and develop some awareness among other pharmaceutical scientists. This review also highlights limitations of these methods applied in industrial setup.

High‐performance thin layer chromatography to assess pharmaceutical product quality

To assess the sustainability, robustness and economic advantages of high-performance thin layer chromatography (HPTLC) for quality control of pharmaceutical products. We compared three laboratories where three lots of cotrimoxazole tablets were assessed using different techniques for quantifying the active ingredient. The average assay relative standard deviation for the three lots was 1.2 with a range of 0.65-2.0. High-performance thin layer chromatography assessments are yielding valid results suitable for assessing product quality. The local pharmaceutical manufacturer had evolved the capacity to produce very high quality products.

Thermal behavior and compatibility analysis of the new chemical entity LPSF/FZ4

In this study, differential scanning calorimetry and thermogravimetry were employed to determine the thermal behavior of LPSF/FZ4 isolated and associated with excipients (amide, β-cyclodextrin, cellulose, lactose, stearate of magnesium, aerosil, sodium lauryl sulfate, polysorbate and polyvinylpyrrolidone). Thus, the purity of the prototype calculated was 98%. Isothermal and non-isothermal methods were used to determine the kinetic parameters of decomposition, finding a first-reaction order and activation energy (Ae) of 98.22kJmol−1. Also, the time of the stability of LPSF/FZ4 was measured in 4 months. The compatibility study showed possible interactions of the prototype with lactose due to a change in its heat of fusion, a reduction of more than 40°C in its stability and a reduction of approximately 30% in Ae of its decomposition reaction. The study demonstrated the importance of using thermal analytical methods to characterize new drugs to enable the development and quality control of pharmaceutical products.

Biological potency evaluation and physicochemical characterization of unfractionated heparins

Unfractionated heparins are used clinically as anticoagulants. The biological potency of thirteen samples of raw material and pharmaceutical formulations were assessed utilizing the 5th International Standard of heparin using the sheep plasma coagulation inhibition assay, activated partial thromboplastin time, anti-factor Xa assay, and anti-factor IIa assay, resulting in mean potencies of 101.15%, 96.15%, 98.15% and 99.37%, respectively. The samples were also evaluated by the protamine neutralization test giving results within the range of 92 - 138 IU/mg. The anti-factor IIa assay was performed showing reproducibility and significant correlation with the pharmacopoeial assays, thus demonstrating it to be a feasible alternative to the sheep plasma coagulation inhibition assay. Moreover, an analysis by nuclear magnetic resonance and capillary electrophoresis showed some peaks attributable to oversulfated chondroitin sulfate. The results show that batch-to-batch variations and the quality of samples contributed to improvements in the quality control of pharmaceutical products and to assure the safe use and clinical efficacy of this biological medicine.

Technique for Enhancing Signal in Conventional Backscattering Fluorescence and Raman Spectroscopy of Turbid Media

We demonstrate experimentally, for the first time, the feasibility of passively enhancing fluorescence and Raman signals from diffusely scattering media in a conventional backscattering collection geometry. The method employs transmission of the collimated excitation laser beam through a "unidirectional" dielectric mirror placed directly in front of the sample. This permits laser light that escapes from the sample surface to be reflected back into the sample where it can be more usefully employed in generating Raman and fluorescence signals. This leads to improved Raman signal, higher signal-to-noise ratio, and shorter acquisition times. Feasibility studies performed on standard pharmaceutical tablets and on sheets of Teflon, using a single enhancing element, demonstrate signal enhancement factors of 6 (fluorescence) and 3 (Raman). Potential applications of this simple device include improving quality control of pharmaceutical products, disease diagnosis of biological tissue, forensics, and security screening.