Substances In Tablets Research Articles

Green RP-HPLC methods for assay and related substances in rivaroxaban tablets

AbstractIn this study, two different ethanol-based RP-HPLC methods for assay and quantification of rivaroxaban related substances in tablets were developed, based on green analytical chemistry (GAC) principles, using the design of experiments approach. The chromatographic separation was performed on X-Bridge C18 column (250 × 4.6 mm, 5 µm particle size), using isocratic elution with ethanol : water (35:65, % v/v) for the assay and gradient elution with ethanol/water mobile phase, for related substances, with a flow rate of 1.0 mL min−1. The gradient method was optimized for the separation of three specified impurities (impurity G, impurity H, and impurity 14) and the selectivity was further confirmed using forced degradation studies. Both methods were validated in accordance with ICH guidelines. The robustness of the methods was confirmed with the Central Composite Face Design of Experiments. Analytical Eco-scale approach and AGREE metrics confirmed that both methods are in accordance with the GAC principles. The proposed ethanol-based RP-HPLC methods were applied for assay and determination of related substances in rivaroxaban 10 mg tablets obtained from three different manufacturers available on the Macedonian market.

A new validated RP-HPLC-UV DAD method for assay of bisoprolol fumarate and related substances in tablets

The research focus of this work was development and validation of an efficient analytical method that can be used for separation and determination of related substances of bisoprolol in finished drug product using reversed-phase HPLC with UV-DAD. In a previous systematic study of various stationary phases and elution conditions it was found that several octadecylsilane phases can be successfully employed for separation of the critical pairs of bisoprolol and its related degradation products. Namely, method development led to conclusions that satisfactory resolution and peak shapes were obtained with gradient elution with water with 0.2% perchloric acid and acetonitrile and the reversed-phase columns: Hypersil 3 BDS C18 (100 x 4 mm, 3 m); Zorbax SB C18 (150 x 4.6 mm, 3.5 m); Acquity UPLC BEH C18 (50 x 2.1 mm, 1.7 m), and Xterra MS C18 (100 x 4.6 mm, 3.5 m). Since regular quality control includes the parameter related substances, which is of great importance for the overall quality of dosage forms, this study was oriented towards widening the available validated analytical methods for determination of this parameter. In this work, the results from the validation of the method for determination of related substances of bisoprolol using Zorbax SB C18 150 x 4.6 mm, 3.5 m, are presented. Validation parameters that were tested (linearity, accuracy, precision, selectivity) confirmed that the method is suitable for its intendance and it was used for characterization of the samples from a forced degradation study of bisoprolol tablets. Keywords: Bisoprolol, RP-HPLC-UV DAD, validation, related substances

Determination of Metoclopramide Hydrochloride in Pharmaceutical Formulations using N-Oxidation Caroate.

To develop two (titrimetric and spectrophotometric) simple, rapid, sensitive and cost-effective methods for the determination of metoclopramide (MCP) in pharmaceutical dosage forms. The titrimetric method (A) was based on the N-oxidation reaction involving the use of potassium hydrogen peroxymonosulfate and subsequent iodometric back titration of a known residual reagent. The spectrophotometric method (B) was based on derivatization of MCP with potassium hydrogen peroxymonosulfate in the presence of iodide to produce a chromogen (triiodide) with a wavelength of maximum absorption at 350 nm. Method "A" was applicable over the concentration range of 0.25-3.5 mg to end volume 10 mL. In method "B", Beer's law was obeyed over the concentration range of 0.3-3.5 μg/mL with molar absorptivity of 24600 L/mol cm. The limits of quantification were calculated to be 0.25 mg/10 mL (A) and 0.2 μg/mL (B), respectively. The proposed methods were suitable for determination of MCP as a pure substance in tablets and injection.

Green HPLC quantification method of lamivudine, zidovudine and nevirapine with identification of related substances in tablets

ABSTRACT A green HPLC method for lamivudine (3TC), zidovudine (AZT) and nevirapine (NVP) determination in fixed-dose combination tablets was developed using ethanol as both one of the mobile phases and the solvent for sample preparation. This method was validated according to ICH Q2(R1) guideline. Additionally, the method was adapted to complete the analysis of five related substances described in the International Pharmacopoeia (Ph. Int.), five other known related substances and two excipients. The separation was obtained with a C18 column (ARV4 5 µm 250 × 3.0 mm, Interchim) using a gradient mode with 0.1M ammonium acetate buffer (pH 4.5) and ethanol as mobile phase at 35°C, a flow rate of 0.4 mL/min, at 270 nm and an injection volume of 10 µL. The combination of ethanol (biodegradable and low-cost alternative solvent) with the use of a column diameter of 3 mm instead of 4.6 mm as used in pharmacopoeias, makes the wastes of the analysis more environmentally friendly and allows the use of a conventional HPLC pump (<400 bar) for easy implementation in quality control in countries with limited resources. Assessment of the method greenness was evaluated using three analytical tools: Analytical Eco-scale, AGREE metrics and Analytical Method Greenness Score (AMGS).

Industrial Applications of THz Imaging Based on Resonant Slit-Type Probe

In this study, the possibility of the industrial application of terahertz (THz) imaging technology was verified. It was applied to the inspection of voids in multistack semiconductors that require safe inspection and to the high-resolution detection and inspection of foreign substances in tablets in the pharmaceutical field. To acquire a high-resolution THz image, a resonant slit probe operating in the THz region was designed, and a high-speed scanning system was established. For the inspection of a multistack semiconductor, a lateral scan method was proposed, and voids with a diameter of 0.5 mm in the multistack semiconductor were detected. In addition, the proposed probe even enables the distinguishment of the positions of voids in the multistack semiconductor. For pharmaceutical inspection, we investigated the application of THz imaging to detect mixed foreign objects frequently occurring in the tablet manufacturing process. For metals, plastics, and rubber, which are the most frequently mixed materials in the tablet manufacturing process, the foreign objects were identified in tablets using a transmission THz system. The measured THz image was compared with the conventional X-ray test result to confirm the potential of THz inspection. In the X-ray image, only metal and some polymer foreign objects were detected. In contrast, in the THz image, although the materials could not be distinguished, most foreign substances were detected. Consequently, the THz imaging test was verified as a possible new tool in fields where X-ray or existing tests are not possible.

Review Article: The Effectiveness of Avocado Seed Starch (Persea Americana Mill) As An Excipients in Tablets Formulation

Avocado consists of pericarp (husk), mesocarp (flesh), and endocarp (seed). In avocado seeds there is a fairly high starch content, which is around 80.1% with amylose content of 43.3% and amylopectin of 36.8%. Starch is defined as a natural polymer consisting of a structure composed of amylopectin and another structure called amylose. Amylose content has properties that are easy to absorb water and amylose content can have excellent swelling power in the tablet crushing process. This allows avocado seeds as an alternative source of starch which can be an excipient in tablets. The research explored the effectiveness of avocado seed starch (Persea americana Mill) as an excipient in tablet formulations based on research that has been done. The method of the research is using secondary data obtained from literature studies, which were analyzed by bibliographic annotation by searching and analyzing data related to the effectiveness of avocado seed starch as an excipient. The data collection technique in this research is in the form of a review of published scientific journals, national and international journals. Analysis of the physical and chemical properties of avocado seed starch showed that avocado seed was able to become an excipient. Several studies also showed that avocado seed starch used as a disintegrant and binder in tablet formulations had an optimum concentration of 10%. In addition, avocado seed starch can also be used as an active substance in tablets.

Modern Approaches to the Technology of Tablet Dosage Forms of Thioctic Acid (Review)

Introduction. Thioctic (α-lipoic) acid is an endogenous antioxidant and is used for liver diseases, poisoning with salts of heavy metals, hyperlipidemia, atherosclerotic heart disease, neuropathy, insulin-resistant forms of diabetes mellitus, etc. technologies for producing tableted medicinal preparations of thioctic acid, necessary for the pharmaceutical development of thioctic acid tablets at pharmaceutical industry enterprises.Text. The review considers the physicochemical properties of the pharmaceutical substance thioctic acid, the features of its pharmaceutical and technological properties, and compatibility with excipients. In the technology of thioctic acid tablets, methods of direct compression and compression with preliminary wet granulation, including those using organic solvents, are used. To increase photostability, thioctic acid tablets are coated. Information on excipients in the composition of core tablets and film coat of thioctic acid tablets registered in Russia is presented. The problems of tabletting thioctic acid are described: sintering of the granulate during the drying process, adhesion of the tabletting mass to the pressing tool and the resulting unevenness of the tablet surface. The ways of optimizing the tabletting process of thioctic acid using various compositions of excipients, improving the flowability of a pharmaceutical substance both during its synthesis and as a result of technological processing, choosing the optimal modes of granulation, drying, pressing are considered.Conclusion. As a result of the analysis of the literature data, the features of the technology for producing thioctic acid tablets were revealed, which are due to the high content of the pharmaceutical substance in tablets (up to 600 mg), the need to use a minimum amount of excipients (from 27 to 51 %), poor flowability, and low melting point of the pharmaceutical substance. Improvement of compressibility and prevention of adhesion can be achieved by using the pharmaceutical substance thioctic acid of a certain granulometric composition, auxiliary substances of the basic nature and a high content of glidants (up to 6 %). The identified manufacturing features should be taken into account in the pharmaceutical development of thioctic acid tablets.

DEVELOPMENT OF HPLC-MS METHOD OF VOGLIBOSE AND QUERCETIN QUANTITATION IN HYPOGLICEMIC ACTION TABLETS

Aim. The purpose of our study was to develop a method for simultaneous quantitation of voglibose and quercetin in a solid dosage form. Materials and methods. The objects of the study were voglibose, quercetin, tablets containing voglibose - 0.2 mg and quercetin 100 mg. Measurements were carried out by high-performance liquid chromatography (HPLC) according to SPHU, supp. 1, 2.2.29, N, using the following equipment: a mass-selective detector Agilent 6530 Q-TOF was used as the detecting system. Results. According to the developed method, the quantitative determination of voglibose and quercetin in the tablets of hypoglycaemic action was investigated. The following results were obtained: the content of C 10 H 21 NO 7 (voglibose) in one dosage unit of the test drug was 0.2 mg; and the content of C 15 H 10 O 7 (quercetin) -0.105 g, which suggests the validability of the proposed method for quantitation of the active substances in tablets for the prevention and treatment of type II diabetes mellitus. Conclusions. In the course of the study, a method was developed for determination of voglibose and quercetin in a hypoglycaemic action preparation using high-performance liquid chromatography (HPLC) with a gradient mode of elution. It has been established that the chosen chromatographic conditions allow quantitative determination of the active pharmaceutical ingredients studied in a solid dosage form with a tolerance of ±5 %. Validation of the developed methodology has been conducted and its suitability for the simultaneous quantification of quercetin and voglibose in tablets has been demonstrated. The reproducibility of this method has been proved.

New Voltammetric Approach to the Quantitation of Paracetamol in Tablets and Syrup using Chemometric Optimization Technique

A new voltammetric approach was developed for the determination of paracetamol in tablet and syrup samples using chemometric optimization. The method is based on the use of the gold nanoparticles–polyaniline (AuNPs−PA) modified pencil graphite electrode (PGE). Electrode system was fabricated by using the electrochemical reduction of gold on aniline modified pencil electrode to give gold nanoparticles. A 33 full factorial design was used to find optimal oxidation conditions of paracetamol on the AuNPs−PA−PGE. The optimal oxidation conditions of drug substance were found as –524 mV for the accumulation potential, 295 s for the accumulation time and pH 8.69 (for the phosphate buffer solution, 0.1 M). The determination of paracetamol was linear in the range of 2.0 × 10–7–6.0 × 10–6 M with a detection limit of 5 × 10–8 M. As a result, the proposed voltammetric approach gave satisfactory results for the determination of the related drug substance in tablets and syrup.

Hydrophilic interaction liquid chromatography in analysis of granisetron HCl and its related substances. Retention mechanisms and method development

In this paper separation of granisetron and its two related substances in HILIC mode is presented. Separation was done on silica column derivatized with sulfoalkylbetaine groups (ZIC-HILIC). Firstly, retention mechanisms were assessed whereby retention factors of substances were followed in wide range of acetonitrile content (80–97%), at constant concentration of aqueous buffer (10mM) as well as at constant pH value of 3.0. Further, in order to developed optimal HILIC method, Design of Experiments (DoE) methodology was applied. For optimization full factorial design 32 was employed. Influence of acetonitrile content and ammonium acetate concentration were investigated while pH of the water phase was kept at 3.3. Adequacy of obtained mathematical models was confirmed by ANOVA. Optimization goals (α>1.15 and minimal run time) were accomplished with 94.7% of acetonitrile in mobile phase and 70mM of ammonium acetate in water phase. Optimal point was in the middle of defined Design Space. In the next phase, robustness was experimetally tested by Rechtschaffen design. The investigated factors and their levels were: acetonitrile content (±1%), ammonium acetate molarity in water phase (±2mM), pH value of water phase (±0.2) and column temperature (±4°C). The validation scope included selectivity, linearity, accuracy and precision as well as determination of limit of detection (LOD) and limit of quantification (LOQ) for the related substances. Additionally, the validation acceptance criteria were met in all cases. Finally, the proposed method could be successfully utilized for estimation of granisetron HCl and its related substances in tablets and parenteral dosage forms, as well as for monitoring degradation under various stress conditions.

HR-MAS NMR for Rapid Identification of Illicit Substances in Tablets and Blotter Papers Seized by Police Department

Illicit substances found in blotter papers and tablets seized by police are traditionally identified and characterized from extracts of these materials. However, the procedures involved in extraction stages can result in artifacts and even contamination of the samples to be analyzed. On the other hand, high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) is a technique that requires no pretreatment steps, enabling direct analysis of the material, including the analysis of new illegal synthetic psychoactive substances. This study presents and discusses applications of the HR-MAS NMR in the analysis of tablets and blotter papers seized. Additional analysis in solution of the extracts of these materials was performed to compare the obtained spectral resolution signals. The results demonstrated that the HR-MAS NMR allowed the rapid identification of 3,4-methylenedioxy-N-methylcathinone (methylone), 4-methylmethcathinone (mephedrone), 2,5-dimethoxy-4-bromoamphetamine (DOB) and 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25B-NBOMe) in samples of tablets and blotter papers seized in Goias State, Brazil.

Determination of oxcarbazepine and its related substances using UHPLC method with UV detection

A simple and rapid ultra - high performance liquid chromatographic (UHPLC) method for the separation and determination of oxcarbazepine and its related substances in tablets, was developed. Chromatographic separation of oxcarbazepine from its related substances (degradation and by-products) was achieved on a reversed phase C18 column (Pinnacle DB C18, RESTEK, 100 x 2.1 mm, 1.9 μm particle size) using gradient program with water (as mobile phase A) and acetonitrile (as mobile phase B), at a flow rate 0.5 mL min-1 and UV detection at 254 nm. The column temperature was 30°C.The method has good selectivity towards oxcarbazepine and its related substances. The accuracy of the method for oxcarbazepine assay, expressed as mean recovery was 101.8 %, and of the method for quantification of degradation products was 95.9 % - 103.3 %. Limit of quantification for oxcarbazepine and its degradation products ranged from 0.60 μg mL-1 to 1.30 μg mL-1. The linearity range for oxcarbazepine assay was from 2.4 to 3.60 mg mL-1 (R2=0.999). Mean value for oxcarbazepine assay from the tablets was 299.92 mg (label claim 300 mg). The method can be used for routine analysis and the quality control of oxcarbazepine drug substance and its formulated products.

A simple spectrophotometric procedure for determination of valaciclovir in dosage forms and biological fluids

A simple and selective spectrophotometric procedure for the determination of Valaciclovir (VALA) is proposed and applied to determine the substance in tablets and biological fluids. This procedure is proposed for the determination of VALA in Britton-Robinson (BR) buffer at pH 6.0, which allows quantification over the 4 × 10−6 to 6 × 10−5 M range for spectrophotometric measurements. The repeatability and reproducibilty of the procedure for serum and breast milk samples are estimated. Precision and accuracy are also checked. The standard additions method is used for biological fluids. The proposed produce was verified for the determination of VALA in real human serum, breast milk samples; the selectivity over the metabolites was found to be quite satisfactory.

Using Terahertz Reflectance Spectroscopy to Quantify Drug Substance in Tablets

The purpose of this research is to investigate the applicability of terahertz (THz) reflectance spectroscopy for quantification of drug substance in tablets, so as to demonstrate the feasibility for applying this technique to tableting process monitoring. In order to acquire a suitable absorbance spectrum for this purpose, it was necessary to enhance the reflection intensity. By using an aluminum plate as a mirror at the opposite surface of the tablet, a reasonable absorbance spectrum could be acquired to reflect the bulk information of the tablet. To assess the limit of tablet thickness, linearity between the tablet thickness and the absorbance value was investigated using lactose and mannitol tablets. Since linearity was found within 0.75-5.0 mm for both tablets using 0.4 and 0.8 THz region, it was confirmed that THz reflectance spectroscopy is applicable to tablets within at least 5.0 mm thickness. Mannitol tablets containing sodium salicylate as the model drug substance were used to investigate the quantitative performance of this technique. It was confirmed that the established calibration model was acceptable for this quantification because of the root-mean-squared error of cross-validation (RMSECV) being 1.95%. In order to evaluate the applicability of this technique, content quantitative performance in double layered tablets having active and placebo layers were assessed. Since this calibration model achieved the root-mean-squared error of prediction (RMSEP) of 1.42% for the double layered tablets, this technique was considered feasible even if the drug substance is localized in the tablets.

Bioavailability of coenzyme Q10 in various pharmaceutical formulations

The bioavailability of coenzyme Q 10 (CoQ 10 ) in various pharmaceutical formulations (solutions and tablets) containing solubilized CoQ 10 in comparison to lipophilic powder of CoQ 10 has been studied in rats. It is established that the bioavailability of solubilized CoQ 10 in tablets and solution after peroral administration is higher than that of lipophilic CoQ 10 powder. The time to reach peak CoQ 10 concentrations in plasma was shorter for the solution of the solubilized form. Auxiliary swelling substances in tablets prolong and increase the absorption of CoQ 10 .

Stability-Indicating RP-HPLC Method Validation of Sertraline Hydrochloride and its Related Substances in Tablets

In the present study, a high-performance liquid chromatographic method was validated to evaluate purity of Sertraline Hydrochloride in tablet dosage form. Sertraline Hydrochloride and two related substances, trans isomer and 2,3-dichloro isomer of Sertraline hydrochloride, were well resolved using a ZORBAX RX C 8 column (250 mm × 4.6 mm, 5) with the mobile phase consisting of 50mM KH 2 PO 4 containing 0.1% octane sulfonic acid sodium salt (pH: 2.5 with Dil. H 3 PO 4 , 0.2% Triethylamine) and methanol (43:57, v/v). Flow rate was kept at 1.0ml/min and the detection was carried out by UV at 215nm. Resolution between any pair of isomers was found to be more than 2. The Limit of detection and Limit of quantification for both trans isomer and 2,3-dichloro isomer of Sertraline Hydrochloride were 10ng/ml and 30ng/ml, respectively. The developed and optimized method was applicable for routine determination of Sertraline Hydrochloride and its trans isomer and 2,3-dichloro isomer in tablet dosage form with sufficient selectivity, precision and accuracy.

Compressibility of Gastroretentive Pellets Coated with Eudragit NE Using a Single-Stroke and a Rotary Tablet Press

In this study, 15 kinds of powders with different compression mechanisms were used in the process of filling-binding substances in tablets with pellets. Applied substances possessed dominant brittle time-independent mechanism or time-dependent viscoplastic, viscoelastic mechanism of compression.Using 6 kN compression force in a single-stroke tablet press during 150 ms of compression, damage to the polymer film and pellet core was found in all formulations. As a result, the authors observed an increase of releasing rate of verapamil hydrochloride (VH). A larger contact area between powders and pellets and connected with this better protective properties were ensured by powders with time-independent compression mechanism (eg, D-sorbitol or D-mannitol). Unsymmetrically applied compression force was a reason for inconsistent densification and insufficient protection of the pellets.Taking into consideration the low rotation speed of the turret (10 rpm) in the rotary tablet press, the total compaction time was much longer than in the single-stroke tablet press. The compression time in the case of the rotary tablet press should be considered as the sum of the precompression (about 130 ms) and main compression (about 280 ms) phase times. Compression force applied by upper and lower punch in the precompression and main compression phase was affected uniformly on the pellets' surface, and when protected against fragmentation, allowed only some slight deformation. The powders in tablet formulation were fragmentized and rearranged independent of their compression mechanisms.It was found that the releasing rate of VH from pellets compressed by rotary tablet press with 6, 12, and 18 kN of compression force was similar to the releasing rate from uncompressed pellets.

Spectrofluorimetric determination of levofloxacin in tablets, human urine and serum

A spectrofluorimetric method to determine levofloxacin is proposed and applied to determine the substance in tablets and spiked human urine and serum. The fluorimetric method allow the determination of 20–3000 ng ml −1 of levofloxacin in aqueous solution containing acetic acid–sodium acetate buffer (pH 4) with λ exc=292 and λ em=494 nm, respectively. Micelle enhanced fluorescence improves the sensibility and allows levofloxacin direct measurement in spiked Human serum (5 μg ml −1) and urine (420 μg ml −1), in 8 mM sodium dodecyl sulphate solutions at pH 5.

Comparison of liquid chromatography, capillary electrophoresis and super-critical fluid chromatography in the determination of Losartan Potassium drug substance in Cozaar® tablets

Reversed phase liquid chromatography, micellar electrokinetic chromatography, and packed column supercritical fluid chromatography were used to measure the amount of Losartan Potassium drug substance in pharmaceutical tablets. Tablet extract samples were analyzed and results were used to compare accuracy, precision, and linearity of calibration of the instrumental techniques. All three techniques have satisfactory precision (less than 1% RSD) and accuracy to be used for the analysis of the drug substance in tablets and the advantages of each technique are discussed.

Separation and determination of lipophilic corticosteroids and benzothiazepin analogues by micellar electrokinetic chromatography using bile salts

The separation of corticosteroids and benzothiazepin analogues by micellar electrokinietic chromatography (micellar EKC) was studied in comparison with capillary zone electrophoresis. The separation of these substances was not successful under neutral and alkaline conditions because they migrated with the same velocity as that of the electroosmotic flow. Micellar EKC with sodium dedecyl sulphate ( SDS) solutions was also not successful because these substances migrated with almost the same velocity as that of the SDS micelle, owing to their high liphophilicity. The use of bile salts, which have a similar skeleton to corticosteroids, as the micellar phase permitted the separation of these substances with high theoretical plate numbers (150 000–350 000) within a short time ( ca. 15 min). Sodium cholate was particulary useful. The effects of bile salt concentration, pH and the addition of methanol were investigated. Micellar EKC was also applied to the determination of the drug substances in tablets and cream using the internal standard method and to purity testing of drug substances and tablets.