Drug Tablets Research Articles

EFFECT OF SOLVENTS IN CHROMATOGRAPHIC DETERMINATION OF SILDENAFIL CITRATE IN MARKETED FORMULATION

Chromatography is the procedure for analysing a multicomponent mixture of trace, minor or major constituent by separaationinto its individual fractions.For the analytical determination of sildenafil in pharmaceutical dosages forms an expeditious & sensitive RP-HPLC method is described.The mobile phase composition for chromatographing sildenafil was acetonitrile: methanol: water(60:25:15, V/V/V) with a flow rate of 1mL/min using C18 column. The internal standard selected was racecadotril and its eluents were observed at 217nm. The retention time was 4.919 min for the drug. Between 5-200μg/mL the linearity of this method was observed. For analysis of drug in tablets, the depicted method was found to be appropriate. The results of the analysis was evaluated statistically. The method were found to be robust, accurate and economic with a major advantage of column longevity, as buffer was not used throughout the method. Hence the proposed method can be extended for routine analysis.

New Potentiometric Screen-printed Sensors for Determination of Trimebutine Drug in Tablets, Serum and Urine Samples.

A new sensit4e and select4e modified screen printed electrodes (MSPEs) and carbon paste electrodes (MCPEs) were studied in order to determine trimbutine maleate (TM) in pure, tablets, urine, and serum samples. These sensors were embodied with multiwalled carbon nanotubes (MWCNTs) since it improved the quality of the sensors in presence of potassium tetrakis (p-chlorophenyl) borate (KTpClPB) ionophore. A good Nernstian response for the constructed sensors, at optimum paste composition, was exhibited for determination of TM in concentration range of 1.5 × 10-7 - 1.0 × 10-2 and 1.0 × 10-7- 1.0 × 10-2 mol L-1 at 25 °C with detection limit of 1.5 × 10-7 and 1.0 × 10-7 mol L-1 for MCPE and MSPE, respect4ely. It seemed that the potential of the electrodes was independent on pH in the range of 2.0-8.0, 2.0-8.5, 2.0-8.5, and 2.0-9.0 g4ing slope as 56.77 ± 1.11, 57.82 ± 0.54, 57.95 ± 0.37, and 58.99 ± 0.28 mV decade-1 for electrodes 1, 2, 3 and 4, respect4ely. MCPEs and MSPEs gave response time about 8 and 6 s with long lifetime (more than 3 and 5 months), respect4ely. A high select4ity of sensors was observed for TM regarding to a large number of interfering species. The constructed sensors were successfully applied for determination of TM in pure form, its pharmaceutical preparations and biological fluids using standard addition, calibration, and potentiometric titration methods with high precision and accuracy. The results showed a good agreement between the proposed method and the HPLC official method.

Ultrasensitive electroanalytical sulfisoxazole sensors amplified with Pd-doped ZnO nanoparticles and modified with 1-hexyl-3-methyl imidazolium bis(trifluoromethylsulfonyl)imide

In this study, an electrochemical sensor has been introduced by incorporating Pd-doped ZnO nanoparticles (ZnO–Pd/NPs) into a carbon paste (CP) matrix amplified by a conductive binder (1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (1H3MIBTMSI), in this case) to determine the concentration of the sulfisoxazole (SFX) drug in urine, tablet, and pharmaceutical wastewater samples.

Ofloxacin-induced fixed drug eruptions

Fixed drug eruption (FDE) is a form of drug induced dermatosis condition. Drugs which most commonly induce FDE are antibiotics, anticonvulsants, antiviral agents and even nonsteroidal anti-inflammatory drugs. Here, we report a case of 50-year-old male with history of hepatosplenomegaly for which he was treated at a regional hospital and was prescribed with tablet ofloxacin (200 mg). The patient visited the pulmonary medicine department of our hospital for respiratory complaints and a dermatological reference was made for skin lesions. The findings concluded the case as a drug-induced FDE with pulmonary tuberculosis (TB). The offending drug (tablet ofloxacin) was withdrawn and suitable treatment was provided for FDE and pulmonary TB. One-month follow-up visit reported no fresh respiratory complaints and resolution of skin lesions. Based on this case report, it can be concluded that though FDE is not a common ADR of ofloxacin, caution must be addressed before prescribing it to the patient. For confirmed cases, it is essential to provide education and counseling to the patient and care giver to prevent its recurrence in future.

Heparin-platinum nanozymes with enhanced oxidase-like activity for the colorimetric sensing of isoniazid

In this study, a colorimetric sensing assay of isoniazid based on excellent oxidase-like activity of heparin sodium stabilized platinum nanoparticles (HS-PtNPs) has been demonstrated. The newly prepared HS-PtNPs exhibit a great dispersion with an average size distribution of 4.8 ± 0.6 nm, and maintain more than 90% catalytic activity under strong acid and alkali or long-term storage conditions, indicating a robust nanomaterial with attractive potential. The HS-PtNPs show distinct oxidase-like activity with an ultrahigh affinity (Km = 0.01012 mM) for 3, 3′, 5, 5′-tetramethylbenzidine (TMB). More significantly, we found that the pyridine ring of isoniazid has a strong reductive hydrazyl substitution, which can compete with TMB for the catalytic site of HS-PtNPs resulting in a colorless solution. Accordingly, a colorimetric sensing of isoniazid was fabricated. A linear relationship for isoniazid was achieved in 2.5 × 10−6 to 2.5 × 10−4 M (R2 = 0.998) with a low limit of detection 1.7 × 10−6 M (S/N = 3). Recovery experiments in drug tablets show that the standard recovery rates were 95%–103%. The quantitative detection data for isoniazid in drug tablets calculated respectively from the standard method and this method exhibited a high correlation coefficient (a slope of 0.9995), suggesting that high accuracy in isoniazid detection.

Improvement of adsorptive voltammetric methods for determination of Midodrine by carbon paste electrode modified with gold nano particles in presence of β-cyclodextrin

An effective novel electrochemical sensor constructed for the determination of Midodrine hydrochloride drug using differential pulse voltammetry. The sensor is based on a carbon paste electrode modified with gold nanoparticles and β-cyclodextrin in Britton-Robinson buffer of pH 3.0. The effect of various experimental parameters on the constructed electrodes properties including pH, β-cyclodextrin concentration and scan rate was investigated. At the optimum conditions, a linear range from 3.0 x 10-6 to 3.2 x 10-4 mol L-1 with correlation coefficient of 0.9997 and a detection limit of 5.14 x 10-7 mol L-1were obtained. The modified electrodes were used for microdetermination of the drug in tablets and spiked human urine samples with appropriate an acceptable recovery, reproducibility, selectivity and robustness. Potential strength investigation was achieved using 0.1 M of HCl.

Automatic Dissolution Testing with High-Temporal Resolution for Both Immediate-Release and Fixed-Combination Drug Tablets

Dissolution testing plays many important roles throughout the pharmaceutical industry, from the research and development of drug products to the control and evaluation of drug quality. However, it is a challenging task to perform both high-efficient separation and high-temporal detection to achieve accurate dissolution profile of each active ingredient dissolved from a drug tablet. In our study, we report a novel non-manual-operation method for performing the automatic dissolution testing of drug tablets, by combining a program-controlled sequential analysis and high-speed capillary electrophoresis for efficient separation of active ingredients. The feasibility of the method for dissolution testing of real drug tablets as well as the performance of the proposed system has been demonstrated. The accuracy of drug dissolution testing is ensured by the excellent repeatability of the sequential analysis, as well as the similarity of the evaluation of dissolution testing. Our study show that the proposed method is capable to achieve simultaneous dissolution testing of multiple ingredients, and the matrix interferences can be avoided. Therefore it is of potential valuable applications in various fields of pharmaceutical research and drug regulation.

VOLTAMMETRIC AND CHROMATOGRAPHIC DETERMINATION OF NAPROXEN IN DRUG FORMULATION

In this work, the electrochemical oxidation of naproxen (NAP) was studied at an ultra-trace graphite electrode (UTGE). The cyclic voltammetry (CV) technique was used to determine the optimum conditions and the effect of pH on the electrochemical oxidation of NAP. Acetate buffer (pH 4.50) was selected as the support electrolyte due to obtaining the highest electronic signal increase during oxidation of NAP at UTGE. The differential pulse voltammetry (DPV) technique was performed for electrochemical determination of NAP. In the optimum conditions, the limits of detection (LOD) and quantification (LOQ) were determined to be 8.6610-8 M and 2.8810-7 M. In addition, the amount of NAP was determined in drug tablets. The recovery studies of NAP from the drug tablet were completed in order to check the accuracy and precision of the applied voltammetric method. Furthermore, the determination of NAP was performed with the high-performance liquid chromatography (HPLC) method. These two methods were compared in terms of accuracy, precision and recovery studies.

On-Demand Manufacturing of Direct Compressible Tablets: Can Formulation Be Simplified?

Oral direct compressible tablets are the most frequently used drug products. Manufacturing of tablets requires design and development of formulations, which need a number of excipients. The choice of excipients depends on the concentration, manufacturability, stability, and bioavailability of the active pharmaceutical ingredients (APIs). At MIT, we developed a miniature platform for on-demand manufacturing of direct compressible tablets. This study investigated how formulations could be simplified to use a small number of excipients for a number of different API's in which long term stability is not required. Direct compressible tablets of five pharmaceutical drugs, Diazepam, Diphenhydramine HCl, Doxycycline Monohydrate, Ibuprofen, and Ciprofloxacin HCl, with different drug loadings, were made using direct compression in an automated small scale system.. The critical quality attributes (CQA) of the tablets were assessed for the quality standards set by the United States Pharmacopeia (USP). This miniature system can manufacture tablets - on-demand from crystalline API using the minimum number of excipients required for drug product performance. All drug tablets met USP quality standards after manufacturing and after 2weeks of accelerated stability test, except for slightly lower drug release for Ibuprofen. On-demand tablets manufacturing where there is no need for long term stability using a flexible, miniature, automated (integrated) system will simplify pharmaceutical formulation design compared to traditional formulations. This advancement will offer substantial economic benefits by decreasing product time-to-market and enhancing quality.

2016. Antibiotic Misuse of Rural Residents and Pilot Project of Antibiotic Take-Back Program

BackgroundSelf-medication with antibiotics (SMA) is a major form of antibiotic misuse behaviors contributing to increasing antimicrobial resistance (AMR). The main source of SMA usually comes from in-home leftover antibiotics which usually disposed as household waste without classification. Therefore, an antibiotic take-back program (ATBP) is urgently needed.MethodsA pilot ATBP was launched in Liantang Village, Zhejiang Province from January to March, 2019. A total of 50 households were randomly selected for the baseline survey. A questionnaire was used to investigate their knowledge and antibiotic use behaviors. Health education leaflets and posters were distributed to each household. A village Wechat group was set up for health communication. Residents were encouraged to hand over those unused or expired antibiotics at home to the village clinic to redeem a commodity. The pilot ATBP was implemented for 30 days. The type, name, and amount of antibiotics were collected as after intervention data.ResultsAll of 50 households finished the questionnaire. Although 27 (52.9%) agreed that keeping antibiotics at home would potentially increase risk of SMA, there were still 32 (64.0%) residents reported that they kept antibiotics at home and 25 (49%) residents indicated that their leftover antibiotics usually disposed as household waste. After the 30-day intervention, 10 (20.0%) households handed their in-home antibiotics or medicine to the village clinic. In total, 32 boxes of medicine including 17 (53.1%) boxes of antibiotics were recycled. All of 32 boxes of medicine could be classified into 19 specific types, of which there were 8 (42.1%) types of antibiotics, belonging to four broad categories: Cephalosporins, Penicillins, Macrolides, and Nitroimidazoles. In addition, there were also antifungal drug, antiviral agent, anti-inflammatory drug, and paracetamol tablets handed over by the villagers as antibiotics.ConclusionUsing leaflets and social media to promote health education can reduce the risk of keeping antibiotics at home. Rural residents could not identify commonly used antibiotics even after health education. To conduct a broader intervention to recycle antibiotics, further study needs to focus on improving the antibiotic identification among the rural residents.Disclosures All authors: No reported disclosures.

Electrodeposition of nickel wrinkled nanostructure from choline chloride:Urea deep eutectic solvent (reline) and application for electroanalysis of simvastatin

Wrinkled nanostructure of nickel was electrodeposited from a deep eutectic solvent comprising choline chloride and urea (reline) under golvanostatic conditions. Field emission scanning electron microscopic images were taken to evaluate the shape and size of the nickel nanostructure. The nickel nanostructure was then converted into the corresponding oxides, and the kinetics of charge transfer across the interface of the nanostructured oxides/an alkaline electrolyte was then studied. The electron transfer coefficient and apparent rate constant for the NiIII/NiII transition in the alkaline electrolyte were attained as 0.53 and 1.0 s−1, respectively. The interaction conditions of nickel redox sites on the surface were also discussed. As an application, electrocatalytic oxidation of simvastatin was studied on the nickel wrinkled nanostructure in the alkaline solution. The oxidation process and its kinetics were investigated by cyclic voltammetry and chronoamperometry. Voltammetric studies indicated that simvastatin was oxidized by NiIII species via an electrocatalytic mechanism. For the electrooxidation of simvastatin, a rate constant of 3.21 × 103 cm3 mol−1 s−1 and an electron transfer coefficient of 0.45 were obtained, while simvastatin diffused in the electrolyte with a diffusion coefficient of 1.80 × 10−6 cm2 s−1. Finally, simvastatin was determined by the nickel wrinkled nanostructure using an amperometry method with a limit of detection of 4.88 μmol L−1 and a calibration sensitivity of 0.035 A L mol−1 cm−2. The determination method was applied for determination of the drug in tablets.

Paper-based colorimetric probe for highly sensitive detection of folic acid based on open-ring form amplification of rhodamine B derivative

A simple colorimetric method was proposed for the determination of folic acid (FA) using a paper-based substrate. The mechanism of the folic acid probe is based on the improvement of electron transfer from the rhodamine B derivative to Cu2+ in the presence of folic acid. Upon the addition of folic acid, the structural conversion of the rhodamine B derivative, in which the spirolactam ring (colorless) was opened little to the open-ring form (pink color) by Cu2+, was amplified clearly. The change of color intensity can be observed by either UV–vis spectrophotometer or naked eye. The color of the paper-based substrate was analyzed using the red, green, blue (RGB) values, which were collected from images captured with a smartphone application. The folic acid paper-based probe exhibited good linearity in the range of 40–260nM with a limit of detection (LOD) of 22nM. The proposed probe exhibits a high potential for detecting folic acid in real samples including drug tablets, human serum, and urine.

Study physico-chemical and biopharmaceutical properties of poor soluble substances for predicting composition and technology of solid dosage forms

Topicality. A detailed study of the physicochemical and biopharmaceutical properties of medicinal substancesshould be carried out at the initial stage of the pharmaceutical development of the finished dosage form of a drug in order to avoid destructive transformations that can occur in the process of manufacture and storage, prediction of bioavailability, pharmacological efficacy and safety of medicinal products in the human body, as well as speed up the scientific work to determine the optimal composition and technology for new drugs.Aim. To study a physico-chemical and biopharmaceutical properties of the poor soluble medicinal substances riluzole and nimodipine for predicting the optimal composition and technology of generic drugs.Materials and methods. Samples of riluzole and nimodipine substances are obtained according to the technology, which is developed by the laboratory of chemical synthesis of the PJSC “Borshchahivskiy CPP”(Kiev, Ukraine) and also samples of tablets original drugs Rilutek, film-coated tablets, 50 mg, company “Sanofi”, France and Nimotop, film-coated tablets, 30 mg, company “Bayer AG”, Germany. All analytical and pharmaco-technological researches were implementedaccording to generally accepted methods that accordance with the requirements of the State Pharmacopoeia of Ukraine.Results and discussion. Physicochemical properties such as the chemical structure of molecules, the size and shape of particles of substances, the possibility of chemical interaction of substances with different excipients, the melting temperature, lipophilicity and solubility in organic and aqueous solvents for the substances riluzole and nimodipine were studied. The study of the biopharmaceutical properties of substances was carried out by study in vitro release kinetics of the substances riluzole and nimodipine from the tablets of the original drugs “Rilutec” and “Nimotop”.Conclusions. Studies of the physico-chemical and biopharmaceutical properties of the medicinal substances riluzole and nimodipine made it possible to predict compatibility of substances with excipients and suggest the most optimal technology for generic drugs Borizol 50 mg film-coated tablets and Nimodipine 30 mg film-coated tablets.

A step in the global effort to control hypertension: Fixed dose combination antihypertensive drugs

Several fixed dose combinations (FDCs) of antihypertensive drugs have recently been added to the World Health Organization model list of essential medications. FDCs have advantages in the management of hypertension compared to single drug tablets including improved adherence, greater blood pressure lowering and are associated with reduced cardiovascular complications. FDCs can also reduce ethnic, and age-related variation in blood pressure lowering and have similar or reduced adverse effects relative to single-drug therapy. Best hypertension control practices from the World Health Organization HEARTS program advocates the use of FDC in simple directive treatment protocols. FDC in simple directive protocols was viewed as a key success factor in the control of chronic infections (eg, tuberculosis, HIV). Unfortunately, implementing simple directive protocols with FDC has had substantial opposition from hypertension experts. Hypertension organizations and experts need to familiarize themselves with best practices in hypertension control, their supporting evidence and to become advocates.

New Spectrophotometric Methods for the Quantification of an Anti-Peptic Ulcer Drug in Bulk and Tablets

New Spectrophotometric Methods for the Quantification of an Anti-Peptic Ulcer Drug in Bulk and Tablets

Rapid and efficient high-performance liquid chromatography analysis of N-nitrosodimethylamine impurity in valsartan drug substance and its products

In July 2018, certain valsartan-containing drugs were voluntary recalled in Japan owing to contamination with N-nitrosodimethylamine (NDMA), a probable human carcinogen. In this study, an HPLC method was developed for the quantitative detection of NDMA simultaneously eluted with valsartan. Good linearity with a correlation coefficient (R2) > 0.999 was achieved over the concentration range of 0.011–7.4 µg/mL. The limits of detection and quantification were 0.0085 μg/mL and 0.0285 μg/mL, respectively. When the recalled valsartan samples were subjected to this method, the observed NDMA contents were in agreement with the reported values, indicating that our method achieved sufficient linearity, accuracy, and precision to detect NDMA in valsartan drug substances and products. Moreover, six samples (valsartan drug substances and tablet formulations), which had a possibility for NDMA contamination, were analyzed; none of the samples contained NDMA at detectable levels. Our method would be useful for the rapid screening and quantification of NDMA impurity in valsartan drug substances and products.

New Technology of Thermoplastic Coating for Osmotic Pump Tablets: Study on in vitro Drug Release

Aim The in vitro drug release profiles of metformin hydrochloride thermoplastic coated tablets and nifedipine thermoplastic coated tablets were studied. Methods By measuring the in vitro release profiles of the thermoplastic coated tablets of model drugs, the effects of membrane thickness, polyethylene glycol-1,500 (PEG1500) content, number of orifice, stirring speed, and release medium on the drug release were investigated, and the rule and mechanism of drug release were also analyzed by comparing with the osmotic pump tablets (OPTs). Results Thermoplastic coated tablets with single- or double-chamber construction performed the same function of controlling the drug release, operated under the same release mechanism (osmotic pressure drove the drug release), and exhibited the same release characteristics (zero-order release, unaffected by release medium, and stirring speed) and release rule (release rate was inversely proportional to the membrane thickness but proportional to the PEG1500 content) as compared with OPTs prepared by the common spray coating technology. Conclusion Thermoplastic coated tablets have the same release characteristics in vitro as OPTs. The new technology of thermoplastic coating can replace the spray coating technology of OPTs. This study provides theoretical basis and practical support for the industrialization and clinical application of thermoplastic coating technology.

A digital indicator system with 7-segment display

This paper presents the design and implementation of a digital system that uses a 7-segment display to indicate the number of drug tablets in a tablet-bottling assembly line. As well as display the number of tablets in a bottle (from 0 – 9), the display can also indicate the name of the vitamin tablet being assembled (Vitamin A, b, C, d, E). This work presents the digital implementation comprising the logic expression, logic circuit and VHDL code for the Vitamin type in the bottle. A digital implementation to display the number of Vitamins in the tablet bottle as well as the Vitamin type with a BBC microbit microcontroller is presented. The application of this work can be extended to give a visual indication of any industrial application that requires indication of the current production stage/phase.

Formulation, Optimization and Evaluation of Bilayer Tablet of Antihypertensive Drug

Hypertension or high blood pressure occurs when the high cardiac output exerts pressure on the arterial wall as the blood flow increases. Bi-layer tablets are prepared with one layer of drug for immediate release while second layer designed to release drug later, either as second dose or in an extended release manner. Bi-layered tablet is suitable for sequential release of two drugs in combination, separate two incompatible substances, and also for sustained release tablet in which one layer is immediate release as initial dose and second layer is maintenance dose. Bilayer tablet is suitable for sequential release of two drugs in combination, separate two incompatible substances and also for sustained release tablet in which one Layer is immediate release as initial dose and second layer is maintenance dose. The preparation of tablets in the form of multi layers is used to provide systems for the administration of drugs.
 Keywords: Hypertension, Bi-layered tablet, Enalapril, Immediate release and Sustained release.

Physicochemical properties and drug-release mechanisms of dual-release bilayer tablet containing mirabegron and fesoterodine fumarate.

Introduction: In this study, a dual release bi-layer tablet containing Fesoterodine fumarate (Fst) 5 mg and Mirabegron (Mrb) 50 mg was prepared to investigate the different release behavior of each drug in bilayer tablet. The bilayer tablet was prepared based on monolayer-tablet formulation of each drug.Methods: The optimized bi-layer tablet showed an in vitro dissolution profile similar to commercial reference tablets Toviaz and Betmiga, based on a satisfactory similarity factor. Drug-release kinetics of each drug in the bilayer tablet were evaluated based on dissolution profiles. Drug-release behavior was evaluated by observing the surface of each layer by scanning electron microscopy and measuring the changes in weight and volume of the tablet during dissolution. Drug transfer between each layer was also investigated by Fourier -transform infrared spectroscopic imaging by observing the cross-section of the bilayer tablet cut vertically during dissolution.Results: The release of Fst was well suited for the Higuchi model, and the release of Mrb was well suited for the Hixson-crowell model. Compared with dissolution rate of each monolayer tablet, that of Fst in the bilayer tablet was slightly reduced (5%), but the dissolution rate of Mrb in bilayer tablet was dramatically decreased (20%). Also, a drug-release study confirmed that polymer swelling was dominant in Fst layer compared with polymer erosion, and degradation was dominant in MRB layer. Fourier-transform infrared imaging and 3-D image reconstruction showed that drug transfer in the bilayer tablet correlates with the results of drug-release behavior.Conclusion: These findings are expected to provide scientific insights in the development of a dual-release bilayer drug-delivery system for Fst and Mrb.