A new three-dimensional (3D) molecularly imprinted polymer fluoroprobe based on green-red dual-emission signals of carbon quantum dots and self-polymerization of dopamine (CDs@PDA-MIPs) for sensitive detection of nifedipine.

Nifedipine (NIF), as one of the dihydropyridine calcium channel blockers, is widely used in the treatment of hypertension. However, misuse or ingestion of NIF can result in serious health issues such as myocardial infarction, arrhythmia, stroke, and even death. It is essential to design a reliable and sensitive detection method to monitor NIF. In this work, an innovative molecularly imprinted polymer dual-emission fluorescent sensor (CDs@PDA-MIPs) strategy was successfully designed for sensitive detection of NIF. The fluorescent intensity of the probe decreased with increasing NIF concentration, showing a satisfactory linear relationship within the range 1.0 × 10-6 M ~ 5.0 × 10-3 M. The LOD of NIF was 9.38 × 10-7 M (S/N = 3) in fluorescence detection. The application of the CDs@PDA-MIPs in actual samples such as urine and Qiangli Dingxuan tablets has been verified, with recovery ranging from 97.8 to 102.8% for NIF. Therefore, the fluorescent probe demonstrates great potential as a sensing system for detecting NIF.

Selective detection of azelnidipine in pharmaceuticals via carbon dot mediated spectrofluorimetric method: A green approach.

A spectrofluorimetric method using fluorescent carbon dots (CDs) was developed for the selective detection of azelnidipine (AZEL) pharmaceutical in the presence of other drugs. In this study, N-doped CDs (N-CDs) were synthesized through a single-step hydrothermal process, using citric acid and urea as precursor materials. The prepared N-CDs showed a highly intense blue fluorescence emission at 447 nm, with a photoluminescence quantum yield of ~21.15% and a fluorescence lifetime of 0.47 ns. The N-CDs showed selective fluorescence quenching in the presence of all three antihypertensive drugs, which was used as a successful detection platform for the analysis of AZEL. The photophysical properties, UV-vis light absorbance, fluorescence emission, and lifetime measurements support the interaction between N-CDs and AZEL, leading to fluorescence quenching of N-CDs as a result of ground-state complex formation followed by a static fluorescence quenching phenomenon. The detection platform showed linearity in the range 10-200 µg/ml (R2 = 0.9837). The developed method was effectively utilized for the quantitative analysis of AZEL in commercially available pharmaceutical tablets, yielding results that closely align with those obtained from the standard method (UV spectroscopy). With a score of 0.76 on the 'Analytical GREEnness (AGREE)' scale, the developed analytical method, incorporating 12 distinct green analytical chemistry components, stands out as an important technique for estimating AZEL.

Targeted and untargeted screening for impurities in losartan tablets marketed in Germany by means of liquid chromatography/high resolution mass spectrometry.

Technical advances in the field of quality analysis allow an increasingly deeper look into the impurity profile of drugs. The ability to detect unexpected impurities in addition to known impurities ensures the supply of high-quality drugs and can prevent recalls due to the detection of harmful unexpected impurities, as has happened recently with the N-nitrosamine and azido impurities in losartan (LOS) drug products. In the present study, the LC-MS/HRMS approach described by Backer et al. was applied to an even more complex system, being the investigation of 35 LOS drug products and combination preparations purchased in 2018 and 2022 in German pharmacies. The film-coated tablets were analysed by means of four LC-MS/HRMS method variants. For the separation a Zorbax RR StableBond C18 column (3.0 ×100 mm, particle size of 3.5 µm, pore size of 80 Å), a gradient elution and for mass spectrometric detection a qTOF mass spectrometer with electrospray ionization in positive and negative mode was used. An information-dependent acquisition method was applied for the acquisition of high-resolution mass spectrometry data. The combination of an untargeted and a targeted screening approach revealed the finding of eight impurities in total. Beside the five LOS related compounds, LOS impurity F, J, K, L, M, and related compound D from amlodipine besilate, LOS azide and an unknown derivative thereof were detected. Identification and structure elucidation, respectively, were successfully performed using in silico fragmentation. Differences in the impurity profiles of drug products from 2018 and 2022 could be observed. This study shows that broad screening approaches like this are applicable to the analysis of drug products and can be an important enhancement of the quality assurance of medicinal products.

Quantitative analysis of drug tablet aging by fast hyper-spectral stimulated Raman scattering microscopy.

Pharmaceutical development of solid-state formulations requires testing active pharmaceutical ingredients (API) and excipients for uniformity and stability. Solid-state properties such as component distribution and grain size are crucial factors that influence the dissolution profile, which greatly affect drug efficacy and toxicity, and can only be analyzed spatially by chemical imaging (CI) techniques. Current CI techniques such as near infrared microscopy and confocal Raman spectroscopy are capable of high chemical and spatial resolution but cannot achieve the measurement speeds necessary for integration into the pharmaceutical production and quality assurance processes. To fill this gap, we demonstrate fast chemical imaging by epi-detected sparse spectral sampling stimulated Raman scattering to quantify API and excipient degradation and distribution.

Sensitive spectrofluorimetric determination of the prokinetic drug prucalopride succinate based on supramolecular aggregation approach with evaluation of method greenness: application to content uniformity test.

The prokinetic drug, prucalopride (PCP) succinate, was determined using a new spectrofluorimetric approach with a highly sensitive, rapid, and simple procedure. The method exploited the enhancement of the inherent native fluorescence of PCP by micellar aggregation with sodium lauryl sulfate (SLS) as an anionic surfactant. Different factors that could affect the fluorescence intensity were carefully studied in order to achieve the maximal fluorescence signal. Measurement of the enhanced fluorescence was done at 354 nm after the excitation at 276 nm. The fluorescence intensity-concentration plot was rectilinear in the concentration range of 50-600 ng/ml with detection and quantitation limits of 13.9 and 42.1 ng/ml, respectively. The method underwent validation according to the International Council for Harmonisation criteria in order to assess its analytical performance, and promising results were achieved that proved the validity and reliability of the method. Furthermore, the method was employed effectively for the analysis of the cited drug in commercial pharmaceutical tablets.

Eco-friendly simultaneous multi-spectrophotometric estimation of the newly approved drug combination of celecoxib and tramadol hydrochloride tablets in its dosage form.

Food and Drug Administration (FDA) recently approved co-formulated celecoxib and tramadol for the treatment of acute pain in adults. Three spectrophotometric methods were efficiently applied to estimate the co-formulated Celecoxib and Tramadol in their tablets; second derivative 2D-spectrophotometry technique (method I), induced dual-wavelength technique (method II) and dual-wavelength resolution technique (method III). The proposed methods were successfully validated following the International Council for Harmonisation (ICH) guidelines and statistically assessed based on the correlation coefficients, relative standard deviations as well as detection and quantitation limits. The obtained results revealed non-significant differences compared to the reported results as revealed by the variance ratio F test and Student t test. Moreover, the applied techniques were further assessed concerning their greenness based on the analytical eco-scale method revealing an excellent green scale with a final score of 95. The proposed spectrophotometric techniques could be applied for the routine analysis and quality control of the studied drugs in their dosage form.

Hydroxyethyl cellulose functionalised with maleimide groups as a new excipient with enhanced mucoadhesive properties.

Hydroxyethylcellulose (HEC) is a non-ionic water-soluble polymer with poor mucoadhesive properties. The mucoadhesive properties of hydroxyethylcellulose can be improved by modifying it through conjugation with molecules containing maleimide groups. Maleimide groups interact with the thiol groups present in cysteine domains in the mucin via Michael addition reaction under physiological conditions to form a strong mucoadhesive bond. This will prolong the residence time of a dosage form containing this modified polymer and drug on mucosal surfaces. In this study HEC was modified by reaction with 4-bromophenyl maleimide in varying molar ratios and the successful synthesis was confirmed using 1H NMR and FTIR spectroscopies. The safety of the newly synthesised polymer derivatives was assessed with in vivo planaria assays and in vitro MTT assay utilising Caco-2 cell line. The synthesized maleimide-functionalised HEC solutions were sprayed onto blank tablets to develop a model dosage form. The physical properties and mucoadhesive behavior of these tablets were evaluated using a tensile test with sheep buccal mucosa. The maleimide-functionalised HEC exhibited superior mucoadhesive properties compared to unmodified HEC.

New Chromatographic Techniques for Sensitive Mebendazole Quantification in the Presence of Degraded Product, Commercial Tablets Application, and Greenness Assessment.

BACKGROUND: Before it spreads to other tissues, mebendazole (MBZ), a highly effective broad-spectrum anthelmintic, is used to treat worm infestations caused by roundworms, hookworms, whipworms, threadworms (pinworms), and the gastrointestinal form of trichinosis. OBJECTIVE: The development of new methods for sensitive quantification of MBZ in the presence of its degraded product is the main objective of the presented research. METHOD: Validated chromatographic techniques with high sensitivity (HPTLC and UHPLC) are used. The HPTLC method was adopted on silica gel HPTLC F254 plates using ethanol, ethyl acetate, and formic acid (3: 8: 0.05, by volume) as a developing system. Furthermore, the UHPLC method is a green isocratic method with a mobile phase containing methanol and 0.1% sodium lauryl sulphate (20:80, v/v). RESULTS: The suggested chromatographic methods are greener than the reported ones in terms of the used greenness assessment methods. To validate the developed methods, International Council on Harmonization (ICH/Q2) guidelines were followed. Successful application of the proposed methods was revealed by the simultaneous analysis of MBZ and its major degradation product, 2-amino-5-benzoylbenzimidazole (ABB). The linear ranges were 0.2-3.0, 0.1-2.0 µg/band for the HPTLC method and 2.0-50, 1.0-40 µg/mL for the UHPLC method for MEB and ABB, respectively. CONCLUSIONS: The suggested methods were used to analyze the studied drug in its commercial tablets. Both pharmacokinetic studies and quality control laboratories can make use of the suggested techniques. HIGHLIGHTS: Green and accurate HPTLC and UHPLC methods for the determination of MBZ and its major degradation products.

Stability-Indicating HPTLC Method for Determination of Remogliflozin Etabonate and Vildagliptin in Tablets.

A sensitive, selective, precise and stability-indicating high-performance thin-layer chromatographic (HPTLC) method is developed for the simultaneous estimation of remogliflozin etabonate and vildagliptin in the presence of their degradation products. The separation was performed in thin layer chromatography plate precoated with silica gel G60F254. The mobile phase consists of methanol:ethyl acetate:toluene:ammonia (1.5:4:4.5:0.1, v/v/v/v). Detection and quantification are performed with densitometer at 212 nm. The Rf values of remogliflozin etabonate and vildagliptin are 0.53 and 0.42, respectively. Degradation studies for the two drugs were carried out in acidic, alkaline, neutral, oxidative, photolytic and thermal stress conditions and analyzed. The suitability of this method for the quantitative determination of the compounds is proved by validation in accordance with the requirements laid down by International Conference on Harmonization (ICH). Linearity was found over the concentration range of 200-1000 ng/band with correlation coefficient of 0.9936 for remogliflozin etabonate and 100-500 ng/band with correlation coefficient of 0.9912 for vildagliptin. The method was successively applied to tablets containing two drugs and found to have no chromatographic interferences from the tablet excipients. The degradant formed was not interfering with estimation of two drugs makes the method more selective for the purpose intended.

Redox-Based Colorimetric Sensor for the Selective Determination of Ascorbic Acid in Fixed-Dose Combination Tablets.

BACKGROUND: Ascorbic acid (ASC; vitamin C) is a weak chromophore, so its presence cannot be determined directly by spectrophotometry. OBJECTIVE: This work aims to develop and validate a simple and ecofriendly analytical method for the determination of ASC concentration based on the reaction of ASC with the metal complex, ferric salicylate. METHODS: The visible absorbance of ferric salicylate was found to be inversely proportional to the concentration of ASC. The possible mechanism of the reaction between ASC and ferric salicylate was investigated: ferric salicylate was found to be reduced by ASC under the applied experimental conditions. Different parameters that may affect the reaction were also investigated: ferric salicylate concentration, pH, ionic strength, and the time of reaction. The optimum concentration of ferric salicylate was found to be 1000 µM and the optimum pH was 5.5. The developed method was validated according to International Conference on Harmonization (ICH) guidelines. RESULTS: The linearity range of the developed method was 5-70 µg/mL and the correlation coefficient was 0.9994. The limits of detection and quantitation were 0.38 µg/mL and 1.16 µg/mL, respectively. The method was successfully applied to the determination of ASC concentration in commercial Ruta-C60® tablets. The mean recovery ± standard deviation was found to be 101.10 ± 0.70%. The results were statistically compared to those obtained by a reported HPLC method. Good agreement was observed. CONCLUSION: The developed method is simple, fast, cost-effective, and suitable for routine pharmaceutical analysis of ASC. HIGHLIGHTS: The developed method is more sensitive than the other spectrophotometric methods reported for determination of ASC.

New HPLC pattern-oriented approach for quality control of enteric coated tablets containing aescin from Aesculus hippocastanum.

From the seed of Aesculus hippocastanum L., a complex mixture of triterpene saponin glycosides known as aescin was isolated, purified and characterized to be an active pharmaceutical ingredient for preparing of drug products. A reversed phase high performance liquid chromatographic method with UV detection was developed for the determination of total triterpene glycosides in enteric coated tablets containing aescin in a pattern-oriented manner. The mobile phase consisted of a mixture of acetonitrile and 0.1 % phosphoric acid solution (40: 60). UV detection was performed at 220 nm. The chromatographic column was Gemini C18 column, 5 µm 250 mm × 4.6 mm, which was maintained at 25 ◦C, connected with a precolumn (C18, 4.0 × 3.0 mm, 5 µm). The linear range was from 53.4 to 160.1 µg·mL-1. The RSD of intra-and inter-day precision variations were less than 1 % and the mean recovery was (100.66 ± 0.49) % (RSD = 0.64 %). The method showed its suitability, simplicity, rapidity and precision. Accordingly, it was proven adequate for quality control of this herbal drug product either for registration with the regulartory authority or routine analysis.

A reversed-phase-high performance liquid chromatography method for simultaneous determination of paracetamol, caffeine, drotaverine HCl and their related impurities with dissolution profiling of their tablets and greenness profile assessment.

A sensitive, specific and eco-friendly reversed-phase-HPLC method was developed and validated for the determination of paracetamol, caffeine and drotaverine HCl along with their related impurities. The separation was accomplished using an X-bridge C18 column (5 µm; 250 mm × 4.6 mm inner diameter) and a green mobile phase consisting of methanol and 0.02 M phosphate buffer at pH 5.0 in the gradient elution mode. The detector used was a diode array detector. The proposed method was validated in accordance with the International Conference on Harmonisation guidelines. Linear regressions were found in the range of 1-100, 1-100, 2-60, 1-20, 0.50-30 and 1-15 µg/mL for paracetamol, caffeine, drotaverine HCl, p-aminophenol, theophylline and 3,4-dimethoxyphenylacetic acid, respectively. The suggested method was successfully applied for the determination of the studied drugs in their tablet dosage form without interference from any excipients. No discernible difference was found between the obtained results and official or reported methods, statistically, in terms of both accuracy and precision. Dissolution profiling of the studied tablet was also performed using the suggested procedure. Moreover, the greenness profile was assessed using three different tools, namely, the National Environmental Methods Index, the Analytical Eco-Scale and the Analytical GREEnness Metric Approach. The acquired results assert the agreement of the assay with green chemistry principles.

Overview of Analytical Methods for Evaluating Tinidazole.

BACKGROUND: Tinidazole (TIN) has amoebicidal, giardicidal, antifungal, and antimicrobial activities. It is marketed in the form of tablets. Analytical methods to assess the quality of TIN-based products are essential for correct pharmacotherapy. OBJECTIVE: The objective of this review is to show an overview of the existing analytical methods for evaluating TIN, according to the quality control (QC) analysis routine and green analytical chemistry (GAC). RESULTS: Official compendia show a method for evaluating TIN in tablets by nonaqueous titration, which has limitations (materials on the mg scale using solvents considered not recommended and harmful). The literature shows some analytical methods for evaluating TIN, both physicochemical and microbiological. The most used physicochemical method is UV (41%), and second is HPLC (28%). Among the microbiological methods, agar diffusion and turbidimetric methods are equally divided. The most studied matrix is TIN tablets (73%), and the most used solvent is methanol. CONCLUSIONS: The literature shows space for the development of analytical methods according to GAC for evaluating TIN, optimizing time, resources, and materials, reducing waste generation, and opting for less aggressive reagents, solvents, and diluents. HIGHLIGHTS: This review shows the status of analytical methods, both physicochemical and microbiological, for the analysis of TIN in pharmaceutical matrix, in the context of routine analysis of the chemical-pharmaceutical industries and of GAC.

Fast and New Microbiological Method for Evaluating the Potency of Marbofloxacin-Based Tablets.

BACKGROUND: Marbofloxacin (MAR) is an antimicrobial belonging to the fluoroquinolone class and is marketed in the form of tablets. There is no microbiological monograph in official compendia to evaluate the potency of the final product. Furthermore, the literature is scarce in this context. OBJECTIVE: The objective is to develop and validate a microbiological method by turbidimetry to evaluate the potency of MAR-based tablets, based on the principles of green analytical chemistry. METHODS: Purified water-ethanol (9 + 1, v/v) was used as diluent to prepare the MAR solutions at concentrations of 0.25, 0.8, and 2.56 µg/mL, brain heart infusion (BHI) broth as culture media, E. coli American Type Culture Collection (ATCC) 25922 at 10% and incubation in a shaker at 37°C for 4 h were used in the method. RESULTS: The method was: linear in the range of 0.25 to 2.56 µg/mL; selective against the sample adjuvants; precise (intra-day RSD 2.26%, inter-day RSD 3.49%, and inter-analyst RSD 3.59%); accurate with a recovery of 100.20%; and robust against changes in culture medium volume in the tube, shaker rotation, and incubation temperature in the shaker. The potency of MAR tablets was 96.98% using the proposed method. CONCLUSION: The turbidimetric method developed is a new, fast, and optimized option to the routine QC of MAR in tablets, since it allows the evaluation of the drug's potency in the final product and can be used to complement the results of the physicochemical analysis, in addition to being a green and sustainable alternative. HIGHLIGHTS: The work shows an ecological and green alternative to the routine microbiological pharmaceutical analysis of MAR tablets.

Near-Infrared data classification at phone terminal based on the combination of PCA and CS-RBFSVC algorithms.

Near-infrared (NIR) spectroscopy is a non-destructive, efficient and convenient detection technology, with the emergence of portable NIR spectrometers, NIR mobile applications (APPs) come into being. The popularity of intelligent mobile phones provides an impetus to the research and development of NIR APPs, however, the primary functions such as operating the NIR spectrometers and collecting data cannot satisfy NIR users in the field of data processing. Herein, we propose an APP processing NIR data locally at the mobile terminal, by the comprehensive utilization of Principal Component Analysis (PCA) and Cuckoo Search algorithm optimized Support Vector Classifier with radial basis function (RBFSVC) kernel (CS-RBFSVC). 738 NIR samples of four drugs (Cydiodine Buccal Tablets, Sulfasalazine Enteric-coated Tablets, Dexamethasone Acetate Tablets, Vecuronium Bromide for Injection) were used as the validation objects to train and test the data classification model. Firstly, the original data were subjected to dimensional reduction through PCA for the purpose of compressing calculation amount. Secondly, the CS-RBFSVC model was utilized to classify the types of drugs and their manufacturers, moreover, the improved accuracy and efficiency by introducing Cuckoo Search (CS) algorithm into RBFSVC were proven in comparison with the conventional grid optimized RBFSVC (Grid-RBFSVC) and Linear Support Vector Classifier (Linear-SVC). Last but not least, an APP based on the proposed PCA and CS-RBFSVC model is developed and demonstrated to be able to classify the type of drugs with an accuracy of 100%, the accuracies of classifying the drugs' manufacturers were 100%, 100%, 98.3% and 90.7%, respectively. Conclusively, the proposed PCA and CS-RBFSVC based model can provide a low-consumption, high accuracy and quick strategy for NIR data classification and overcome the limitations of internal storage and operating speed at phone terminals, in conjunction with the portable NIR spectrometer, it is believed to push forward NIR technology into the instant detection and on-site inspection.

Validated stability indicating chromatographic method for determination of baricitinib and its degradation products in their tablet dosage form: Implementation to content uniformity and in vitro dissolution studies.

OBJECTIVES: Newly, baricitinib (Olumiant) is FDA-confirmed for treating adult patients with slightly to highly active rheumatoid arthritis who have a terrible reaction to several treatments against the tumor necrosis factor. The efficacy and safety of baricitinib have been determined by the FDA, so, a precise, and sensitive stability-indicating RP-HPLC method is issued to determine baricitinib and its degradation products in their film-coated tablet dosage form; application to content uniformity and in-vitro dissolution studies. METHODS: The analysis of assay and dissolution tests are released using an isocratic elution system while impurities are performed using gradient profile for mobile phase comprising of Buffer Solution: Methanol in Proportion (65:35, v/v) at flow rate 1.0mL/minute, column BDS Hypersil C18 5µm 150×4.6mm, column temperature 30̊C, injection volume 10µL, detection wavelength 290nm using DAD detector. RESULTS: Calibration charts are acquired in the linearity range (1-30µg/mL) of baricitinib with a correlation coefficient=0.9999 with good recovery results between (99-100%). CONCLUSION: The proposed procedure was fully validated regarding Linearity, Accuracy, LOD, LOQ, Precision, Robustness, and Specificity, and there is no overlapping owing to deterioration peaks. Furthermore, the method has been accomplished to study content uniformity testing and in-vitro dissolution.

Statistical process control of manufacturing tablets for antiretroviral therapy

Abstract In this study, the manufacturing process of lamivudine (3TC) and zidovudine (AZT) tablets (150+300 mg respectively) was evaluated using statistical process control (SPC) tools. These medicines are manufactured by the Fundação para o Remédio Popular "Chopin Tavares de Lima" (FURP) laboratory, and are distributed free of charge to patients infected with HIV by the Ministry of Health DST/AIDS national program. Data of 529 batches manufactured from 2012 to 2015 were collected. The critical quality attributes of weight variation, uniformity of dosage units, and dissolution were evaluated. Process stability was assessed using control charts, and the capability indices Cp, Cpk, Pp, and Ppk (process capability; process capability adjusted for non-centered distribution; potential or global capability of the process; and potential process capability adjusted for non-centered distribution, respectively) were evaluated. 3TC dissolution data from 2013 revealed a non-centered process and lack of consistency compared to the other years, showing Cpk and Ppk lower than 1.0 and the chance of failure of 2,483 in 1,000,000 tablets. Dissolution data from 2015 showed process improvement, revealed by Cpk and Ppk equal to 2.19 and 1.99, respectively. Overall, the control charts and capability indices showed the variability of the process and special causes. Additionally, it was possible to point out the opportunities for process changes, which are fundamental for understanding and supporting a continuous improvement environment.

Analytical Quality by Design-Based Robust RP-HPLC Method for Quantitative Estimation of Pregabalin and Etoricoxib in Fixed-Dose Combination Tablet Formulation.

BACKGROUND: The Central Drugs Standard Control Organization approved a bilayered, uncoated, fixed-dosage combination tablet formulation containing pregabalin (75 mg) and etoricoxib (60 mg) in November 2019 to control prolonged back pain with neuropathic components. OBJECTIVE: This research aims to create an analytical quality by design-assisted reversed phase (RP)-HPLC method for quantifying pregabalin and etoricoxib in tablet formulation. METHODS: The best chromatographic conditions were a Phenomenex C8 column (250 × 4.6 mm, 5.6 µm) and a mobile phase of 0.35% orthophosphoric acid -acetonitrile (1 + 1, by volume). A flow rate of 1 mL/min was used with a detection wavelength of 220 nm. RESULTS: The optimized reversed phase HPLC method was successfully validated by the International Conference on Hormonization guideline Q2(R1). Moreover, the percentage assay of pregabalin and etoricoxib tablet formulation was 99.05 and 100.02% w/w, respectively, using the validated RP-HPLC method. CONCLUSION: The newly developed analytical quality by design-assisted RP-HPLC method has several advantages, including shortened analytical time (2.65 min and 7.45 min pregabalin and etoricoxib, respectively), efficient separation in terms of well-defined peaks, and a simple mobile phase combination. HIGHLIGHTS: The use of analytical quality by design principles and the design of the experiment tool allowed the detection of influential parameters critical for achieving the most favourable chromatographic conditions for accurately quantifying individual drugs using the RP-HPLC method. The compliance of the results with the ICH criteria validated the method. As a result, adopting the analytical quality by design methodology ensured the development of a more robust method that can generate consistent, dependable, and quality data throughout the process while also saving time.

Simultaneous Determination of Paracetamol, Ibuprofen, and Caffeine in Tablets by Molecular Absorption Spectroscopy Combined with Classical Least Square Method.

In this paper, the classical least-squares (CLS) method with molecular absorption spectrophotometric measurement was used to determine simultaneously paracetamol (PAR), ibuprofen (IBU), and caffeine (CAF) in tablets. The absorbance spectra of the standard solutions and samples were measured over a wavelength from 220 to 300 nm with a 0.5 nm step. The concentration of PAR, IBU, and CAF in the sample solutions was calculated by using Visual Basic for Applications (VBA) and a program called CLS-Excel written in Microsoft Excel 2016. The method and the CLS-Excel program were tested on mixed standard laboratory samples with different PAR, IBU, and CAF concentration ratios, and they showed only small errors and a satisfying repeatability. An analytical procedure for tablets containing PAR, IBU, and CAF was developed. The reliability of the procedure was proved via the recovery and repeatability of the analysis results with an actual tablet sample and by comparing the mean contents of active substances in the tablets obtained from the analytical procedure with the HPLC method. The procedure is simple with a reduced cost compared with the HPLC standard method.

Evaluation of laser direct infrared imaging for rapid analysis of pharmaceutical tablets.

Vibrational spectroscopic chemical imaging is an important tool in the pharmaceutical industry for characterising the spatial distribution of components within final drug products. The applicability of these techniques is currently limited by the long data acquisition times required to obtain high-definition chemical images of a sample surface. Advancements in quantum cascade laser (QCL) technology have provided an exciting new opportunity for infrared (IR) imaging. Instead of collecting a full IR spectrum at each point, it is possible to focus on distinct spectral bands to reduce imaging data collection time. This study explores a laser direct infrared (LDIR) chemical imaging approach that couples QCL technology with rapid scanning optics to provide high-definition chemical images at an order of magnitude faster than traditional imaging techniques. The capabilities of LDIR chemical imaging were evaluated for pharmaceutical formulations and compared with other established spectroscopic chemical imaging techniques including Raman, near-infrared (NIR) and scanning electron microscopy-energy dispersive X-ray (SEM-EDX) spectroscopy with regards to data acquisition time and image quality. The study showed that LDIR imaging provided high-definition component distribution maps comparable to Raman and SEM-EDX at orders of magnitude faster in terms of time. The ability to obtain high-definition chemical images of the whole tablet surface in relatively fast time frames indicates LDIR imaging could be a promising tool in the pharmaceutical industry to rapidly characterise the size and distribution of components within tablets and could help enhance drug product manufacturing understanding.