Pharmaceutical Unit Research Articles

A simple eco-friendly spectrofluorimetric resolution approach for the simultaneous determination of Naproxen and Domperidone in pharmaceutical formulation and human plasma; assessment of method greenness

Designing new verified methods for the determination of pharmaceutical compounds in their specified formulation without prior separation and with high sensitivity taking in consideration analytical performance and simplicity has become a major concern of pharmaceutical quality control units. In the present work, a new simple and eco-friendly spectrofluorimetric method was developed and validated for the determination of Naproxen (NAP) and Domperidone (DOM) in their binary mixture, pharmaceutical formulation in addition to human plasma without prior separation. The proposed method is based on measuring the second derivative fluorescence intensity for NAP at 345 nm and for DOM at 292 after excitation at 235 nm without any interference from each other. All the variables affecting fluorescence intensity were studied and optimized. The proposed method showed excellent sensitivity with limit of detection (LOD) 12.286 ng/mL and 3.240 ng/mL for NAP and DOM respectively. In compliance with the ICH requirements, the optimized method was validated and was successfully utilized for the determination of both drugs in their pharmaceutical formulation and human plasma. Finally, the greenness of the proposed method was assessed using different assessment tools.

The influence of thermal radiation during microwave-assisted freeze-drying of pharmaceutical unit doses

New drying technologies for biologicals have recently been developed to accelerate the time-consuming batch freeze-drying (BFD) process. Among others, microwave-assisted freeze-drying (MFD) has been suggested as a faster and more effective drying technology. In this study, MFD cycles with the microwave radiation switched on and off were performed to assess the contribution of the microwave radiation to drying acceleration. It was found that thermal radiation emitted by the drying chamber walls was predominantly accelerating the drying of monodose placebos rather than microwave radiation. The combination of ultra-low chamber pressure, high thermal heat transfer and a short primary-to-secondary phase transition reduces drying times by more than 80 % compared to conventional BFD. In a second step, a design of experiment approach was used to assess the effect of thermal radiation versus microwave radiation and their combination, together with dosage properties such as fill volume and excipient concentration upon drying rate. The outcome showed the importance of high fill volume and high excipient concentration for an effective microwave contribution to the drying rate. Nevertheless, the drying acceleration for small pharmaceutical dosages with restricted solutes was mainly driven by thermal radiation rather than 2.45 GHz microwave radiation. The inability of ice to convert microwave energy into heat hampers the potential use of microwave freeze-drying for single-dose vaccines.

The Influence of Business Location and Service Quality on Consumer Loyalty with Consumer Satisfaction as a Mediating Variable at PT Giri Aneka Usaha (Perseroda) Giri Husada Wonogiri Pharmacy Unit

The objective of this research is to: 1) test and measure the impact of service quality and business location on customer satisfaction. 2) test and mitigate the effect of quality of service and business site on consumer loyalty. The research was carried out at the Aneka Usaha (Perseroda) Pharmaceutical Unit at Husada district of Wonogiri. The population in this study is the entire customer of Pharmacy Giri Husada. Given the unknown distribution of the population, according to Cooper and Schindler the number of samples taken was 96 rounded to 100 respondents. Research finds that there is an influence on the quality of service and the location of the business on consumer satisfaction. The quality of the service and the location of the business influence the loyalty of the consumer. Consumer satisfaction mediates the quality of the customer service against the loyalty of the consumer, but consumer satisfaction does not mediate the quality of service against the customer loyalty.

Mise en place d’une antenne pharmaceutique de blocs opératoires dans un centre hospitalier universitaire

An operating room pharmaceutical unit centralizes medical devices and drugs for various surgical specialities. The aim of this work is to present the methodology used in our establishment to set up the operating room pharmaceutical unit. This approach involved the formation of multi-professional working groups. The needs of operating theatres were defined based on an analysis of healthcare product consumption and stock inventories. Material sheets were defined for each procedure. On the basis of simulations, material supply arrangements were selected, specifying material flows, equipment, workstations and information systems. Over 3200 healthcare product references were identified and 862 equipment files were created. Local stocks have been limited to medical trolleys for nursing staff. Emergency operating packs have been deployed for unforeseen operations. Cabinets have been dedicated to transporting re-sterilizable medical devices, and carts have been purchased for programmed operating packs. The equipment is made available by logistics agents and pharmacy assistants under pharmaceutical responsibility. This innovative approach is a model for facilities desiring to centralize and secure the logistics of healthcare products in the operating room. Ongoing adjustments will be required to meet new operating rooms needs.

Predicting pharmaceutical prices. Advances based on purchase-level data and machine learning

BackgroundIncreased costs in the health sector have put considerable strain on the public budgets allocated to pharmaceutical purchases. Faced with such pressures amplified by financial crises and pandemics, national purchasing authorities are presented with a puzzle: how to procure pharmaceuticals of the highest quality for the lowest price. The literature explored a range of impactful factors using data on producer and reference prices, but largely foregone the use of data on individual purchases by diverse public buyers.MethodsLeveraging the availability of open data in public procurement from official government portals, the article examines the relationship between unit prices and a host of predictors that account for policies that can be amended nationally or locally. The study uses traditional linear regression (OLS) and a machine learning model, random forest, to identify the best models for predicting pharmaceutical unit prices. To explore the association between a wide variety of predictors and unit prices, the study relies on more than 200,000 purchases in more than 800 standardized pharmaceutical product categories from 10 countries and territories.ResultsThe results show significant price variation of standardized products between and within countries. Although both models present substantial potential for predicting unit prices, the random forest model, which can incorporate non-linear relationships, leads to higher explained variance (R2 = 0.85) and lower prediction error (RMSE = 0.81).ConclusionsThe results demonstrate the potential of i) tapping into large quantities of purchase-level data in the health care sector and ii) using machine learning models for explaining and predicting pharmaceutical prices. The explanatory models identify data-driven policy interventions for decision-makers seeking to improve value for money.

Formulation and Evaluation of Different Polymer-Coated Spherules from Granules

Abstract: A novel spheronization technique is reported here for forming spherules from granules using FDA-approved excipients and common pharmaceutical unit operations. Aspirin is used as a drug to check stability during the process. Spherules are made by “bed coating during sliding” (BCDS) of granules. The spherules provide an opportunity to modify their surface properties by polymer film coating. It improves the functional properties such as appearance, drug release, and integrity of particles during the processing of spherules. Spherules with two size ranges (sieves no 22 and 44) are compared. These spherules are further coated with polymers to show the adaptability of the process. Microscopical evaluation reveals that several edges (90° and 45°) are less for spherules compared to granules. The angle of Repose and packing parameters appeared excellent. Different polymer coating drugs give different release profiles as per the properties of the polymeric drugs. This is a versatile platform delivery system for developing advanced drug delivery systems (ADDS). However, the stability of aspirin is affected by the wet process may be because aspirin is a hydrolytically labile drug. Granules and pellets are not necessarily spherical. Coated spherules can also be an option for coating as against to coating the tablet.

A framework for the practical development of condition monitoring systems with application to the roller compactor

Implementing a condition-based maintenance strategy requires an effective condition monitoring (CM) system that can be complicated to develop and even harder to maintain. In this paper, we review the main complexities of developing condition monitoring systems and introduce a four-stage framework that can address some of these difficulties. The framework achieves this by first using process knowledge to create a representation of the process condition. This representation can be broken down into simpler modules, allowing existing monitoring systems to be mapped to their corresponding module. Data-driven models such as machine learning models could then be used to train the modules that do not have existing CM systems. Even though data-driven models tend to not perform well with limited data, which is commonly the case in the early stages of pharmaceutical process development, application of this framework to a pharmaceutical roller compaction unit shows that the machine learning models trained on the simpler modules can make accurate predictions with novel fault detection capabilities. This is attributed to the incorporation of process knowledge to distill the process signals to the most important ones vis-à-vis the faults under consideration. Furthermore, the framework allows the holistic integration of these modular CM systems, which further extend their individual capabilities by maintaining process visibility during sensor maintenance.

Characterization by MALDI-TOF MS and 16S rRNA Gene Sequencing of Aerobic Endospore-Forming Bacteria Isolated from Pharmaceutical Facility in Rio de Janeiro, Brazil.

Bacillus and related genera are among the most important contaminants in the pharmaceutical production environment, and the identification of these microorganisms at the species level assists in the investigation of sources of contamination and in preventive and corrective decision making. The aim of this study was to evaluate three methodologies for the characterization of endospore-forming aerobic bacterial strains isolated from a pharmaceutical unit in Rio de Janeiro, Brazil. MALDI-TOF MS was performed using MALDI Biotyper® and VITEK® MS RUO systems, and complete 16S rRNA gene sequencing was performed using the Sanger methodology. The results showed the prevalence of the genera Bacillus (n = 9; 36.0%), Priestia (n = 5; 20.0%), and Paenibacillus (n = 4; 16.0%). Three (20.0%) strains showed <98.7% of DNA sequencing similarity on the EzBioCloud Database, indicating possible new species. In addition, the reclassification of Bacillus pseudoflexus to the genus Priestia as Priestia pseudoflexus sp. nov. is proposed. In conclusion, 16S rRNA and MALDI TOF/MS were not sufficient to identify all strains at the species level, and complementary analyses were necessary.

Effectiveness of hospital-based oral dextrose gel in prevention and treatment of asymptomatic newborns at risk of hypoglycemia

Objective To evaluate the effectiveness of using hospital-based 40% dextrose gel (DG) in preventing and treating asymptomatic hypoglycemia in infants of diabetic mothers (IDM), large for gestational age (LGA), and macrosomic neonates. Methods A medical chart review was conducted to compare data between before (April 2018 to March 2019, epoch 1) and after (September 2020 to November 2021, epoch 2) 40% DG implementation. DG, prepared by the hospital pharmaceutical unit, was applied within 30–45 min after birth, and three additional doses could be repeated during the first 6 h of life in combination with early feeding. The primary outcome was the rate of intravenous dextrose administration. Secondary outcomes were the incidence of hypoglycemia, first capillary blood glucose concentrations, and the length of hospital stay. Results Six hundred forty-three at-risk newborns were included (320 before and 323 after implementation of DG). Maternal and neonatal baseline characteristics were not different between the two epochs. The incidence of hypoglycemia was not different (17.8% in before versus 14.6% in after implementation, p = 0.26). The rate of intravenous dextrose administration after DG implementation was significantly lower than that before DG implementation (3.4% versus 10.3%, p < 0.001, risk reduction ratio = 0.33, 95% CI = 0.17–0.64). The length of hospital stay was not different between the two epochs. Conclusions Implementing a protocol for administration of hospital-based 40% DG can reduce the need of intravenous dextrose administration among IDM, LGA and macrosomic neonates.

Design space determination of pharmaceutical processes: Effects of control strategies and uncertainty

The identification of process Design Space (DS) is of high interest in highly regulated industrial sectors, such as pharmaceutical industry, where assurance of manufacturability and product quality is key for process development and decision-making. If the process can be controlled by a set of manipulated variables, the DS can be expanded in comparison to an open-loop scenario, where there are no controls in place. Determining the benefits of control strategies may be challenging, particularly when the available model is complex and computationally expensive – which is typically the case of pharmaceutical manufacturing. In this study, we exploit surrogate-based feasibility analysis to determine whether the process satisfies all process constraints by manipulating the process inputs and reduce the effect of uncertainty. The proposed approach is successfully tested on two simulated pharmaceutical case studies of increasing complexity, i.e., considering (i) a single pharmaceutical unit operation, and (ii) a pharmaceutical manufacturing line comprised of a sequence of connected unit operations. Results demonstrate that different control actions can be effectively exploited to operate the process in a wider range of inputs and mitigate uncertainty.

Analysis of the effect of formulation properties and process parameters on granule formation in twin-screw wet granulation

In the last few years, twin-screw wet granulation (TSWG) has become one of the key continuous pharmaceutical unit operations. Despite the many studies that have been performed, only little is known about the effect of the starting material properties on the stepwise granule formation along the length of the twin-screw granulator (TSG) barrel. Hence, this study obtained a detailed understanding of the effect of formulation properties (i.e., Active Pharmaceutical Ingredient (API) properties, formulation blend particle size distribution and formulation drug load) and process settings on granule formation in TSWG. An experimental set-up was used allowing the collection of granules at the different TSG compartments. Granules were characterized in terms of granule size, shape, binder liquid and API distributions. Liquid-to-solid (L/S) ratio was the only TSG process parameter impacting the granule size and shape evolution. Particle size and flow properties (e.g., flow rate index) had an important effect on the granule size and shape changes whereas water-related properties (e.g., water binding capacity and solubility) became influential at the last TSG compartments. The API solubility and L/S ratio were found to have a major impact on the distribution of binder liquid over the different granule size fractions. In the first TSG compartment (i.e., wetting compartment), the distribution of the API in the granules was influenced by its solubility in the granulation liquid.

Inorganic Metal Oxides and Multi-Component Nanocomposites Based Photocatalysts for the Superior Degradation of Pollutants from Water

Water is a primary and essential source of every living organism and it is a most precious gift of Mother Nature which helps every living creature to survive. However, this water is highly polluted now-a-days by various unethical activities by human beings. Many industrial units like textile mills, pharmaceutical units, mines, paper mills, dyeing units, sugar industries, leather purifying units, electroplating plants, fine chemical units, oil refineries, etc. produce huge amount waste products in the form of toxic chemicals and pollutants every day and enter the water bodies without proper treatment. Various techniques are available to purify the polluted water by eliminating the toxicity of pollutants; some of them are reverse osmosis, electrode ionization, ion exchange, submicron filtrations, etc. Among all these water treatment procedures, photocatalysis is found to be most versatile, low cost and environmentally benign technique. In this review, a prime focus is given on the performance of different photocatalysts based on ZnO, CuO, NiO, SnO2, MgO, multicomponent metal oxides and composites in degrading and removing unwanted impurities present in polluted water. The importance of using metal oxide based photocatalyts in treating the polluted water is also discussed.

Analysis of Drug Availability Management at the Regional General Hospital Pharmacy Installation

Pharmacy managerial activities are inseparable from the principles of drug availability management such as a series of needs planning activities, procurement, storage and distribution of drugs through hospital pharmacy installations. This study aims to analyze and obtain information on availability management at the Pharmacy Installation of the South Tapanuli Regional General Hospital. This type of research is qualitative with a descriptive approach using primary data and secondary data using the interview method. The informants interviewed at the pharmaceutical installation were the head of the pharmaceutical installation unit, the coordinator of pharmacy services, the head of the pharmaceutical warehouse/supplies, the coordinator of quality management and administration. Informants of this study were taken by purposive sampling and data analysis using triangulation and data reduction methods. The results of this study obtained that planning for drug needs uses the consumption method by looking at the need for previous use, but it has not been maximized, procurement has not gone well, drug shortages often occur, drug storage systems use the FIFO (First in First Out) and FEFO (First Expired First Out) systems. First Expired First Out). Storage is not up to standard, the waiting time for drug distribution to patients starting from the patient submitting the prescription to the delivery of the drug takes quite a long time for the drug to be finished. The conclusion is that the implementation of drug availability management has not run optimally according to standard operating procedures for services, so it is necessary to increase human resource knowledge through training related to drug planning.

Three Innovative Green and High-Throughput Microwell Spectrophotometric Methods for the Quantitation of Ceritinib, a Potent Drug for the Treatment of ALK-Positive Non-Small Cell Lung Cancer: An Application to the Analysis of Capsules and Drug Uniformity Testing.

Ceritinib (CER) is a potent drug that has been recently approved by the Food and Drug Administration for the treatment of patients with non-small cell lung cancer harboring the anaplastic lymphoma kinase mutation gene. The existing methods for the quality control of CER are very limited and suffer from limited analytical throughput and do not meet the requirements of the green analytical principles. This study presented the first-ever development and validation of three innovative green and high-throughput microwell spectrophotometric methods (MW-SPMs) for the quality control of CER in its dosage form (Zykadia® capsules). These MW-SPMs were based on the formation of colored N-vinylamino-substituted haloquinone derivatives of CER upon its reactions with each of chloranil, bromanil, and 2,3-dichloro-1,4-naphthoquinone in the presence of acetaldehyde. The optimized procedures of the MW-SPMs were established, and their analytical performances were validated according to the ICH. The linear range of the MW-SPMs was 5-150 µg/mL, with limits of quantitation of 5.3-7.6 µg/mL. The accuracy and precision of the MW-SPMs were proved, as the average recovery values were 99.9-101.0%, and the relative standard deviations did not exceed 1.8%. The three methods were applied to the determination of CER content in Zykadia® capsules and drug content uniformity testing. The greenness of the MW-SPMs was proved using three different metric tools. In addition, these methods encompassed the advantage of high-throughput analysis. In conclusion, the three methods are valuable tools for convenient and reliable application in the pharmaceutical quality control units for CER-containing capsules.

Development of Two Novel One-Step and Green Microwell Spectrophotometric Methods for High-Throughput Determination of Ceritinib, a Potent Drug for Treatment of Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer.

Background and Objectives: Ceritinib (CER) is a potent drug of the third-generation tyrosine kinase inhibitor class. CER has been approved for the treatment of patients with non-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase (ALK) mutation gene. In the literature, there is no green and high-throughput analytical method for the quantitation of CER in its dosage form (Zykadia® capsules). This study describes, for the first time, the development and validation of two novel one-step and green microwell spectrophotometric methods (MW-SPMs) for the high-throughput quantitation of CER in Zykadia® capsules. Materials and Methods: These two methods were based on an in microwell formation of colored derivatives upon the reaction of CER with two different benzoquinone reagents via two different mechanisms. These reagents were ortho-benzoquinone (OBQ) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), and their reactions proceeded via condensation and charge transfer reactions, respectively. The reactions were carried out in 96-well transparent plates, and the absorbances of the colored reaction products were measured with an absorbance microplate reader at 540 and 460 nm for reactions with OBQ and DDQ, respectively. The optimum conditions of reactions were established, their molar ratios were determined, and reaction mechanisms were postulated. Under the refined optimum reaction conditions, procedures of MW-SPMs were established and validated according to the guidelines of the International Council on Harmonization. Results: The limits of quantitation were 6.5 and 10.2 µg/well for methods involving reactions with OBQ and DDQ, respectively. Both methods were applied with great reliability to the determination of CER content in Zykadia® capsules and their drug uniformity. Greenness of the MW-SPMs was evaluated using three different metric tools, and the results proved that the two methods fulfil the requirements of green analytical approaches. In addition, the simultaneous handling of a large number of samples with microvolumes in the proposed methods gave them the advantage of a high-throughput analysis. Conclusions: The two methods are valuable tools for rapid routine application in pharmaceutical quality control units for the quantitation of CER.

Dual fluorescence enhancement of loratidine by photoinduced electron transfer blocking and micellization: Application to the development of novel highly sensitive microwell spectrofluorimetric assay for analysis of dosage forms and urine samples

This study describes the enhancement of the weak native fluorescence of loratadine (LOR) by dual strategy via photoinduced electron transfer (PET) blocking followed by micellization into sodium dodecyl sulfate micelles. The enhanced fluorescence was employed as a basis for the development of a novel microwell spectrofluorimetric assay (MW-SFA) for the determination of LOR in its pharmaceutical dosage forms and urine samples. The assay was conducted in 96-microwell assay plates, and the enhanced fluorescence signals were measured by a microplate reader at 290 and 435 nm for excitation and emission, respectively. The optimum conditions of the assay were established, calibration curve was generated, and the linear regression equation was computed. The relation between the fluorescence signals and LOR concentrations was linear with good determination coefficients (0.9992) in the range of 10 – 2000 ng mL−1. The assay limits of detection and quantitation were 4.1 and 12.5 ng mL−1, respectively. The precision was satisfactory, with values of relative standard deviation not exceeding 1.68%, and the assay’s accuracy was ≥ 99.1%. The proposed was successfully applied to the analysis of LOR in its pharmaceutical dosage forms with acceptable accuracy and precision. The label claims were 99.3 – 100.5% (±0.95 – 1.59%). Statistical analysis comparing the results of the proposed assay with those obtained by a reported pre-validated assay revealed no significant difference between both methods in terms of the accuracy and precision at the 95% confidence level. The assay was also applied to the analysis of urine samples containing LOR with accuracy ≥ 98.24%. The greenness of the proposed assay was confirmed by three efficient metric tools. In overall conclusion, the proposed assay is characterized by high sensitivity, procedure simplicity, and high throughput, enabling the simultaneous analysis of many samples in a short time. Therefore, it is a valuable tool for rapid routine application in pharmaceutical quality control units and clinical laboratories for the determination of LOR.

Development and Validation of Green and High-Throughput Microwell Spectrophotometric Assay for the Determination of Selective Serotonin Reuptake Inhibitors in Their Pharmaceutical Dosage Forms.

This study describes the development and validation of a new green and high-throughput microwell spectrophotometric assay (MW-SPA) for the determination of three selective serotonin reuptake inhibitors (SSRIs) in their pharmaceutical dosage forms. These SSRIs are fluoxetine, fluvoxamine, and paroxetine, the most prescribed drugs for the treatment of depression. The proposed assay was based on the formation of orange-colored N-substituted naphthoquinone derivatives upon the reaction of SSRIs with 1,2-naphthoquinone-4-sulphonate (NQS) in alkaline media. The assay was conducted in 96-microwell assay plates, and the absorbances of the reaction products were measured by a microplate reader at their maximum absorbance wavelengths. The optimum conditions of the reaction were refined and established. Under these conditions, calibration curves were generated, and linear regression equations were computed. The linear relations between the absorbances and drug concentrations were linear with good correlation coefficients (0.9992-0.9997) in the range of 2-80 µg/mL. The assay limits of detection were in the range of 1.5-4.2 µg/mL. The precision was satisfactory as the values of relative standard deviation did not exceed 1.70%. The accuracy of the assay was ≥98.2%. The proposed MW-SPA was successfully applied to the analysis of the SSRIs in their pharmaceutical dosage forms with acceptable accuracy and precision; the label claims were 99.2-100.5% (±0.96-1.35%). The results of the proposed MW-SPA were compared with those of the official/pre-validated assays by statistical analysis with respect to the accuracy (by t-test) and precision (by F-test). No significant differences were found between the calculated and theoretical values of the t- and F-tests at the 95% confidence level, proving similar accuracy and precision in the determination of SSRIs by both assays. The greenness of the proposed assay was confirmed by two metric tools. In addition, the assay is characterized with a high-throughput property which enables the simultaneous analysis of many samples in a short time. Therefore, the assay is a valuable tool for rapid routine application in pharmaceutical quality control units for the determination of the investigated SSRIs.

Impact of autoclavation on baked-on siliconized containers for biologics

Many pharmaceutical manufacturing units utilize pre-sterilized ready-to fill primary containers for parenterals. The containers may have been sterilized by the supplier via autoclavation. This process can change the physicochemical properties of the material and the subsequent product stability. We studied the impact of autoclavation on baked on siliconized glass containers for biopharmaceuticals. We characterized the container layers of different thickness before and after autoclavation for 15 min at 121 °C and 130 °C. Furthermore, we analyzed the adsorption of a mAb to the silicone layer and subjected filled containers to 12 weeks storage at 40 °C monitoring functionality and subvisible particle formation of the product. Autoclavation turned the initially homogenous silicone coating into an incoherent surface with uneven microstructure, changed surface roughness and energy, and increased protein adsorption. The effect was more pronounced at higher sterilization temperatures. We did not observe an effect of autoclavation on stability. Our results did not indicate any concerns for autoclavation at 121 °C for safety and stability of drug/device combination products using baked-on siliconized glass containers.

Development of green and high throughput microwell spectrophotometric and spectrofluorimetric assays for quantitation of roscovitine in its bulk form and capsules

Roscovitine (RCV) is a drug with potential for the treatment of different types of cancer, neurodegenerative disease, renal dysfunction, viral infections, and chronic inflammatory disorders. This study describes, for the first time, the development and validation of three novel microwell-based assays for quantitation of RCV in its bulk form and capsules. These assays are two spectrophotometric assays and one spectrofluorimetric assay. The first spectrophotometric assay (UV-SPA) is based on measuring the native ultraviolet (UV) radiation absorption of RCV. The second assay (CT-SPA) is based on the formation of colored charge transfer (CT) complex upon the reaction of RCV, as n-electron donors, with 2,5-dichloro-3,6-dihydroxybenzoquinone (CHBQ), as a π-electron acceptor. The spectrofluorimetric assay (NF-SFA) is based on measuring the native fluorescence of RCV. These three assays were carried out in 96-microwell assay plates, and the signals were measured by a microplate reader. The optimum conditions of the three assays were established and their analytical performances were validated according to the guidelines of the International Council for Harmonization (ICH) for validation of analytical procedures. The linear ranges for the three assays were 10–300 µg mL1, 25–800 µg mL1 and 25–500 ng mL1 for UV-SPA, CT-SPA and NF-SFA, respectively. The limits of detection (LOD) of the assays were 4.1 µg mL1, 8.8 µg mL1 and 9.2 ng mL1 for UV-SPA, CT-SPA and NF-SFA, respectively. The accuracy and precision of the three assays were proved as the recovery values were ≥98.8%, and the relative standard deviations (RSD) did not exceed 2.32%. The three assays were successfully applied to the quantitation of RCV in its bulk form and capsules; the mean recovery values were ≥99.5%. The greenness of the assays was evaluated by three different metric tools, and the results proved that the three assays fulfill the requirements of green analytical approaches. In addition, the simultaneous handling of large number of samples with micro-volumes in the proposed assays gave these assays the property of high throughput analysis. In conclusion, the three assays are valuable for the rapid routine application in the pharmaceutical quality control units for the quantitation of RCV.

One-Step Microwell Plate-Based Spectrofluorimetric Assay for Direct Determination of Statins in Bulk Forms and Pharmaceutical Formulations: A Green Eco-Friendly and High-Throughput Analytical Approach

This study describes the development of a one-step microwell spectrofluorimetric assay (MW-SFA) with high sensitivity and throughput for the determination of four statins in their pharmaceutical and formulations (tablets). These statins were pitavastatin (PIT), fluvastatin (FLU), rosuvastatin (ROS) and atorvastatin (ATO). The MW-SFA involves the measurement of the native fluorescence of the statin aqueous solutions. The assay was conducted in white opaque 96-microwell plates, and the fluorescence intensities of the solutions were measured by using a fluorescence microplate reader. The optimum conditions of the assay were established; under which, linear relationships with good correlation coefficients (0.9991-0.9996) were found between the fluorescence intensity and the concentration of the statin drug in a range of 0.2-200 µg mL-1 with limits of detection in a range of 0.1-4.1 µg mL-1. The proposed MW-SFA showed high precision, as the values of the relative standard deviations did not exceed 2.5%. The accuracy of the assay was proven by recovery studies, as the recovery values were 99.5-101.4% (±1.4-2.1%). The assay was applied to the determination of the investigated statins in their tablets. The results were statistically compared with those obtained by a reference method and the results proved to have comparable accuracy and precision of both methods, as evidenced by the t- and F-tests, respectively. The green and eco-friendly feature of the proposed assay was assessed by four different metric tools, and all the results proved that the assay meets the requirements of green and eco-friendly analytical approaches. In addition, ever-increasing miniaturization as handling of large numbers of micro-volume samples simultaneously in the proposed assay gave it a high-throughput feature. Therefore, the assay is a valuable tool for the rapid routine application in the pharmaceutical quality control units for the determination of statins.