Preparation Of Tablets Research Articles

A Bioequivalence Study of Azilsartan in Healthy Chinese Subjects.

Azilsartan is an angiotensin II receptor blocker used for treating adult hypertension. It significantly improves cardiovascular outcomes in patients with high-risk hypertension, heart failure, and diabetic nephropathy. A single-center, randomized, open-label, single-dose, dual-cycle, dual-crossover clinical trial was conducted to evaluate the bioequivalence of azilsartan under fasting and postprandial conditions in 60 Chinese healthy volunteers. Thirty healthy subjects were enrolled in each test group, with random cross-administration for fasting and postprandial tests. The concentration of azilsartan in human plasma was evaluated using liquid chromatography-tandem mass spectrometry after a single oral administration of test and reference preparations, each at a dose of 20mg (1 tablet). Pharmacokinetic parameters were determined using WinNonlin8.2 software, and bioequivalence was evaluated using SAS 9.4 software. The geometric mean ratios and 90% confidence intervals for maximum concentration, area under the plasma concentration-time curve from time 0 to the time of last measurable concentration, and area under the plasma concentration-time curve from time 0 to infinity of the test and reference preparations in the fasting and postprandial test groups were in the range of 80%-125%. The incidence of adverse events in the fasting and postprandial test groups was 30% (9/30) and 33.3% (10/30), respectively. No serious adverse events or unexpected adverse drug reactions were observed. In conclusion, the test and reference preparations of azilsartan tablets demonstrate bioequivalence and good safety in healthy Chinese subjects under fasting and postprandial conditions.

Preparation and Evaluation of Anti-Emetic Ginger Orodispersible Tablets from Standardized Extract using Phenolic Profile Effects

Preparation and Evaluation of Anti-Emetic Ginger Orodispersible Tablets from Standardized Extract using Phenolic Profile Effects

2-(3-(Chloromethyl)benzoyloxy)benzoic Acid reduces prostaglandin E-2 concentration, NOX2 and NFKB expression, ROS production, and COX-2 expression in lipopolysaccharide-induced mice

IntroductionInflammation is a fundamental response to various insults, including microbial invasion and tissue injury. While aspirin (ASA) has been widely used for its anti-inflammatory properties, its adverse effects and limitations highlight the need for novel therapeutic alternatives. Recently, a novel salicylic acid derivative, 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3-CH2Cl), has emerged as a potential substitute for ASA, offering a simpler, environmentally friendly synthesis and a promising safety profile. Aim of the studyThis research aims to evaluate the anti-inflammatory mechanism of 3-CH2Cl in a lipopolysaccharide (LPS)-induced mouse model, focusing on its effects on prostaglandin E-2 (PGE-2) concentration, NOX2 and NFkB expression, ROS production, and COX-2 expression. Material and methodsUtilizing BALB/C mice subjected to LPS-induced inflammation, we investigated the therapeutic potential of 3-CH2Cl. The study included synthesis and tablet preparation, experimental design, peripheral blood plasma PGE-2 measurement, splenocyte isolation and COX-2 expression analysis, nitric oxide and ROS measurement, and immunohistochemical analysis of NOX2 and NFkB expression. Results3-CH2Cl significantly reduced PGE-2 levels (p = 0.005), NO concentration in liver homogenates (p = 0.005) and plasma (p = 0.0011), and expression of NOX2 and NFkB in liver (p < 0.0001) and splenocytes (p = 0.0036), demonstrating superior anti-inflammatory activity compared to ASA. Additionally, it showed potential in decreasing COX-2 expression in splenocytes. Conclusion3-CH2Cl exhibits potent anti-inflammatory properties, outperforming ASA in several key inflammatory markers in an LPS-induced inflammation model. The reduction of COX-2 expression, alongside the reduction of pro-inflammatory cytokines and oxidative stress markers, suggest it as a promising therapeutic agent for various inflammatory conditions.

Study of Citric Acid-Locust Bean Gum as a Glidant to Fillers of Cellulose Derivatives

Citric acid-locust bean gum (CA-LBG) was introduced as an excipient in tablet preparations. CA-LBG is a compound derived from the esterification of citric acid (CA) with locust bean gum (LBG). The experiment aimed to determine the potential and effect of CA-LBG as a glidant on microcrystalline cellulose (MCC). The CA-LBG concentrations in the experiments were 0.5%, 1.0%, 2.0%, and 4.0%. Talc and magnesium stearate (MgS) as a comparison. The mixtures were evaluated for flow rate and angle of repose. The mixture was compressed into tablets weighing 700 mg. Tablets were evaluated for weight, hardness, and friability. The flow rate of the mixture containing CA-LBG 0.5%-4.0% was 12.77 g.sec-1-15.96 g.sec-1. The angle of repose of the mixture containing CA-LBG 0.5%-4.0% is 32.62○-35.52○. The weight of tablets containing CA-LBG 0.5%-4.0% is 700.0 mg-701.2 mg. The hardness of tablets containing CA-LBG 0.5%-4.0% is 6.30 kp-6.90 kp. The friability of tablets containing CA-LBG 0.5%-4.0% is 0.17%-0.36%. The CA-LBG has the potential as a glidant in MCC fillers. Increasing CA-LBG concentration causes the flow rate to increase, the angle of repose to decrease, and the hardness to increase. CA-LBG concentrations of 0.5% and 4.0% reduced tablet friability.

Phytochemical Screening and Evaluation of Anti Diabetic Activity Using Momordica charantia (Leaf &amp; Stem) Extracts in Alloxan Induced Rats

Purpose: Current procedure is to find out the effect of anti-diabetic using Momordica Charantia (leaf and stem) extracts on Alloxan induced experimental rats. Methods: The leaf and stem extracts of Momordica charantia were prepared by using cold maceration technique. The obtained filtrates are then subjected to a distillation process to obtain pure and concentrated products. The phytochemical studies were performed for both the extracts. Wet granulation method was done for preparation of tablets. The α-Amylase inhibition assay was done to both leaf and stem extracts as an in vitro method and Alloxan induced anti diabetic method was done as an in vivo process for the experimental animals. At last creatinine and urea levels were estimated. Results: The phytochemical results of both leaf and the stem extracts were shown positive for phenols, tannins, flavonoids, glycosides, steroids, oils, fats and for alkaloids. The weight of the granules were reduced and found to be F1- 15.32gm, for granules F2-14.37gm, for granules F3-14.39gm and for granules F4- it was 13.83gm. For α-amylase inhibition assay the standard acarbose 58.70% of inhibition for 100 μg/ml concentrations, the leaf extract showed 80.58% of inhibition for 100μg/ml concentration and the stem extract showed 86.45% of inhibition for 100μg/ml concentration. In fasted rats for the extract-1 (leaf) the highest blood glucose level was seen at 0 min as 82(mg/dl) and for the extract-2(stem) the highest blood glucose level was seen at 0 min as 84(mg/dl). And for the Oral glucose tolerance test the extract-1(leaf) the highest blood glucose level was seen at 120 min as 119(mg/dl) and for the extract-2(stem) the highest blood glucose level was seen at 120 min as 108(mg/dl). Conclusion: The study attests to the therapeutic effects of the chosen plant extracts, which have been demonstrated to help prevent and regulate blood glucose levels. Furthermore, in managing diabetes and its associated problems. Momordica charantia plant extracts from the leaves and stems have demonstrated anti-hyperglycemic properties. The results of this investigation indicated that there was a notable antidiabetic response to the treatment using plant extracts (leaf &lt; stem).

Formulation Optimization and Preparation of Amlodipine and Telmisartan Double-layer Tablets (5/40Mg) using Wet Granulation Method

The two-layer tablet of amlodipine and telmisartan is an effective strategy to manage hypertension disease through a combination of various treatment mechanisms. However, the spray-drying method is currently used to prepare telmisartan tablets due to its extremely low solubility, which requires sophisticated equipment. In this study, wet granulation was applied to fabricate this two-layer tablet. Furthermore, design of experiments were deployed to design and optimize the formulation in order to obtain an in-vitro equivalence with the reference drug. As a result, a formulation of the two-layer table using the wet granulation method was successfully developed and optimized. The obtained tablet showed an in-vitro equivalence with the reference drug (with f2 superior to 50 for both amlodipine and telmisartan). Furthermore, the obtained tablet also met a set of in-house standards, including appearance, identification, assay, and dissolution rate. This study provided not a novel but effective and simple method of fabrication for amlodipine-telmisartan tablets using wet granulation. Furthermore, the obtained results also highlighted the significant contribution of a well-established design of experiments in the development of a complex tablet formulation.

FORMULATION AND EVALUATION OF LOSARTAN POTASSIUM MATRIX TABLETS BY USING DIFFERENT POLYMERS

The study aims to create a sustained release matrix tablet for Losartan potassium, an angiotensin II receptor antagonist, to improve patient compliance and maintain therapeutic blood or tissue levels for extended periods. The research investigates the role of novel semi-synthetic polymers and natural polymers in comparison to well-known release retarding agents. Gastroretentive drug delivery systems (GRDDS) are unique technologies designed to improve drug bioavailability and absorption by avoiding the first-pass effect. Losartan potassium, an angiotensin II receptor antagonist, has a bioavailability of 32% and a low elimination half-life, making it suitable for oral controlled release. The study utilized natural and synthetic polymers in matrix tablet preparation, concentration, drug particles size, additives, and excipients to modify drug release. The powder mixtures were tested for pre-compression parameters and post-compression parameters, and in-vitro dissolution studies showed good dissolution profiles for drug release. Formulations with higher concentrations and polymers sustained drug release for 24 hours. FT-IR Spectroscopy confirmed drug compatibility with polymers and other excipients KEYWORDS: matrix tablets, Losartan Potassium, flow properties, pre compression parameters post compression parameters, In-vitro dissolution.

How oregano essential oil can be transformed into a taste-masking controlled release solid formulation

Oregano essential oil (OEO) has antioxidant, antiproliferative, anti-inflammatory and antimicrobial activities. OEO could be administered orally for some gastrointestinal diseases, however, its oral use, is severely hampered by its irritant taste, which requires a high dilution in water before administration, and by its high susceptibility to light and humidity. Moreover, phenols have a high instability during digestion, and are rapidly metabolized, so that only a small fraction of the oral dose reaches the lower gut. Protection of OEO from degradation in the gastrointestinal tract is essential for its enhanced efficacy and sustained release The aim of this work has been the preparation and characterization of tablets based on hydroxypropyl methylcellulose (HPMC) granules containing OEO adsorbed on zeolite and coated with Eudragit® E PO to protect the oil from instability. Measurements of angle of repose demonstrated that OEO-containing zeolite granules were not cohesive and could be easily compressed. The obtained coated tablets had sufficient mechanical strength and were able to prevent the oxidation of polyphenols in the stomach, indeed only the 15 and 30 % of them was released in simulated jejunal and ileal fluid, respectively. These solid dosage forms protect phenols contained in OEO from degradation and volatilization, as suggested by TG analysis.

Preparation and Evaluation of Metronidazole Tablets Produced with Different Binders Using Wet Granulation Method

In tablet formulation, binders are essential for ensuring proper powder mix, granulation and overall tablet quality. Variations in binder quality and concentration can impact drug bioavailability, strength and manufacturing processes. The inconsistency in bioavailability and therapeutic response of metronidazole from different manufacturers highlights the importance of binder selection in tablet formulation. This study evaluates the impact of different binding agents on tablet quality. The optimum binder concentration for each of the binders was assessed to obtain suitable concentration that was used to prepare metronidazole tablets. Metronidazole tablets were formulated with four different binder vis, acacia, gelatine, PVP, maize starch at 3% concentration using wet granulation method after which the tablet properties were evaluated. Metronidazole powder exhibited poor flow indices, as indicated by angle of repose: 39.92 ± 1.85, Carr’s compressibility index (CI): 20.13 ± 0.28 and Hausner’s ratio (Hr): 1.26 ± 0.01, whereas its granules exhibited good flow properties. The crushing strength (CS), friability (FR), disintegration time (DT) (CSFR/DT) ratio for batches showed values in 3% binder concentration, indicating higher strength as compared to other concentrations. There was a significant increase (P &lt; 0.05) in the CSFR/DT ratio for gelatine (2.22) in formulation F2 compared to maize starch in Formulation F4. The formulated tablets with the various binders have met with the British Pharmacopeial criteria of 80% drug release from uncoated immediate-release tablets. Amongst the four binders, gelatine was found to be the best in the formulation of robust metronidazole tablets by wet granulation method at an optimised concentration of 3% w/w. Tablets produced with gelatin exhibited greater mechanical strength than those produced with other binders, while also demonstrating a slightly longer DT. Metronidazole tablets produced with gelatine have met the British Pharmacopeial requirements including an acceptable in-vitro drug release profile.

Preparation of orodispersible tablets of bosentan using xylitol and menthol as dissolution enhancers

Bosentan is a drug used to treat pulmonary hypertension via dual endothelial receptor antagonism. Bosentan has a restricted oral bioavailability, a problem that's mostly due to poor solubility and hepatic metabolism. It is extensively used for the elderly and children who require a friendly dosage form like orodispersible tablets. So, the goal of this research work was to hasten the dissolution rate of bosentan to produce an orodispersible tablet with immediate drug release. Bosentan was exposed to ethanol-assisted kneading with a rise of xylitol or menthol concentrations (1:1 and 1:2 molar ratio of bosentan with excipient). In addition to observing the dissolution behavior, the resulting dry products were investigated using Fourier transform infrared spectroscopy (FTIR), differential thermal analysis (DTA), and X-ray diffraction (XRD). The FTIR reflected possible hydrogen bonding with xylitol and menthol. DSC studies reflected a reduction in the enthalpy and Tm. These results with XRD data reflected partial co-amorphization in the case of xylitol and eutaxia in the case of menthol. These modifications were related to an accelerated dissolving rate. The developed systems were fabricated as orodispersible tablets which exhibited immediate release of bosentan. Thus, the current study offered simple co-processing for the preparation of orodispersible bosentan tablets.

3D printing of multi-unit gastro-retentive tablets for the pulsatile release of artesunate

Pulsatile drug delivery is hardly achieved by conventional gastro-retentive dosage forms. Artesunate as a typical anti-malaria medicine needs oral pulsatile release. Here, artesunate-loaded pulsatile-release multi-unit gastro-retentive tablets (APGTs) were prepared with a semi-solid extrusion three-dimensional (3D) printing method. An APGT was composed of three units: artesunate-loaded immediate and delayed release units and a block unit. The matrix of the immediate/delayed release units consisted of polyvinylpyrrolidone (PVP) K30 and croscarmellose sodium, which improved the rapid release of artesunate when contacting water. The block unit consisted of octadecanol, hydroxypropyl methyl cellulose K15M, PVP K30, and poloxamer F68. APGTs showed multi-phase release in simulated gastric liquids (SGLs). The first immediate release phase continued for 1 h followed by a long block phase for 7 h. The second rapid release phase was initiated when the eroded holes in the block unit extended to the inner delayed release unit, and this phase continued for about 14 h. Low-density APGTs could ensure their long-term floating in the stomach. Oral APGTs remained in the rabbit stomach for about 20 h. 3D printing provides a new strategy for the preparation of oral pulsatile-release tablets.

Exploration and preparation of ofloxacin biphasic tablets via semi-solid extrusion technology

Biphasic-release systems have garnered significant attention for their ability to rapidly achieve blood levels and maintain therapeutic efficacy. This study aimed to use Semi-solid Extrusion (SSE) technology to design and manufacture a biphasic-release tablet containing ofloxacin, with the objective of enhancing patient compliance. Additionally, it demonstrated that 3D printing technology offered distinct advantages in preparing biphasic formulations. A series of biphasic-release tablets with varying ratios or positions of the immediate-release portion and sustained-release portion were prepared using common excipients like HPMC and lactose. These variations in ratios and positions had a significant impact on drug release. Furthermore, all 3D-printed tablets exhibited unique internal structures and could float for 12 h in a dissolution medium. The biphasic-release tablets exhibited satisfying hardness and friability, satisfying the demands of storage and transportation. Analysis of XRD, DSC, and FTIR data indicated the absence of detectable interaction forces between the active pharmaceutical ingredient (API) and the excipients, and the physical state of API remained unaffected. TGA data indicated minimal residual solvent content in the 3D-printed tablets. Overall, this study demonstrated the potential utilization of SSE technology in developing personalized clinical treatment using biphasic tablets.

3D-printed immediate release solid dosage forms: a patent evaluation of US11622940B2.

Three-dimensional (3D) printing is one of the most flexible technologies for preparing tablets, offering controlled drug release profiles. The current patent describes the preparation of immediate-release 3D-printed tablets of hydrochlorothiazide to improve disintegration and dissolution profile. The patent involves the preparation of drug-loaded filament via hot-melt extrusion and utilizing the same filaments for printing 3D-printed tablets using fused deposition modeling. The tablets were printed with different shapes and sizes by incorporating channels within the tablet spaces, termed as gaplets. The introduction of channels within the tablet design improves the disintegration and dissolution profile of the drug significantly. The morphological characteristic of 3D-printed tablets was studied by using scanning electron microscopy and revealed the presence of gaplets in the tablets.

Infrared Fourier Transform Spectroscopy Method for Analysis of Valsartan and Amlodipine Besylate Combination

This study investigates the analysis of the combination of Valsartan and Amlodipine besylate using the Infrared Fourier Transform and its quantitative calculations by chemometrics based on partial least squares with several variables. A calibration model has been formulated, and absorbance besylate measurements at wave numbers of 1634-1566 cm-1 for valsartan and 1127-1059 cm-1 for amlodipine every 2.0 cm-1. Then simultaneously determine valsartan and amlodipine combined in the tablet preparation. The Infrared Fourier Transform method used for Amlodipine besylate and Valsartan with calibration are y = 13.1317 X -0.0595 and y = 129,731 X - 0.026. The validation parameters is 0.9995, and 0.9999 for R2 values, RMSCEV is 0.02427 and 0.003189, and PRESS is 0.02121 and 0.0003662. Prediction ability was still acceptable and good for determination. The levels result were (101.52±2.74)% and (98.47±5.71)%, and valid with Relative Standard Deviation (RSD) respectively 2%, and average recovery percent obtained in range of 98-102%. The method identified provided guaranteed compliance with USP 43-NF 38 (2020).

Preparation of a long-lasting tablet of spinosad microspheres and its residual insecticidal efficacy against the yellow fever mosquito, Aedes aegypti (Diptera: Culicidae) larvae.

In order to provide a long-lasting formulation for spinosad (SP) targeting larval stages of Aedes aegypti (Linnaeus) and others alike, a SP tablet was developed based on microspheres, using polylactic acid as inside coating material. The microspheres were encapsulated using polyethylene glycol and 1-hexadecanol to form a sustained-release SP tablet. Micromorphology, active ingredient loading, structure identification, photolysis resistance and biological activity were evaluated in this report. (i) The SP microspheres had an average particle size of 6.16 ± 2.28 μm, low adhesion and good dispersion as evaluated by scanning electron microscopy and morphology. (ii) The average active ingredient loading and encapsulation of SP microspheres were 32.80 ± 0.74% and 78.41 ± 2.22%, respectively. (iii) The chemical structure of encapsulated SP was confirmed by Fourier transform infrared and 1H-nuclear magnetic resonance. (iv) The photostability of the microspheres and the tablets were evaluated. The results showed that DT50 (time required to dissipate 50% of the mass originally present) of SP was 0.95 days in microspheres and 6.94 days in tablets. (v) The long-term insecticidal activity of SP tablets was investigated, and the tablet had a long-lasting activity against the mosquito larvae, showing 100% larval mortality for 63 days. The study provided a new long-lasting formulation of SP, which displayed good efficacy in the control of Ae. aegypti larvae. © 2024 Society of Chemical Industry.

The feasibility of Raman spectroscopy for accurate assessment of essential criteria in pharmaceutical industry by investigation of Metformin hydrochloride tableting process

AbstractAnalytical and real‐time technology in pharmaceutical manufacturing process is an important need to ensure that manufactured drugs are safe and effective. Raman spectroscopy is an emerging technique that is able to perform quantitative analysis nondestructively due to the molecular structure of many drugs. Monitoring the content uniformity and quantification of active pharmaceutical ingredient (API) in the tablet preparation process, without the assistance of solvent, is one of the key concerns in the formulation design in order to provide stable, pure, and homogenous finished products. In this study, we investigated the possibility of using Raman data as an analytical method to quantify API, the intra‐ and inter‐sample uniformity of content in the tableting process of Metformin hydrochloride tablets (C4H11N5.HCl). Analysis of all standard samples for prediction of API uniformity represents an acceptable accuracy and precision with a relative standard deviation of 2.55%. Further investigation of tablets regarding to relative Raman intensity of some characteristic peaks demonstrates the amount of API content with an accuracy of ≥96%. These values have a good adaption with pharmacopeia monograph. Findings reveal that the Raman method can be routinely utilized for quantifying API, controlling the content uniformity and the stability of drugs in different stages of manufacturing.

Preparation and Evaluation of Sustained Release Matrix Tablets of Acelofenac and Comparision of Formulated and Marketed Product

The aim of performing this study is to develop matrix tablet to improve the dissolution rate of aceclofenac and release the drug in a controlled manner over a period of 24 hours. Matrix tablets of aceclofenac, using various viscosity of hydrophilic polymer HPMC in two different proportions, hydrophobic polymer ethyl cellulose and Guar gum were prepared by wet granulation method and subjected to in vitro drug release studies. Tablets were evaluated for in vitro drug release profile in phosphate buffer with pH 7.5. The thickness and hardness of prepared tablets were 3.8 ± 0.2 to 3.9 ±0.2 mm and 4 ± 3 to 5 ± 3 kg/cm2, respectively. The friability was within the acceptable limits of pharmacopeial specifications (0.31 to 0.71%), which indicates the good mechanical strength of the tablets. The in vitro drug release from the proposed system was best explained by Higuchi’s model, indicating that drug release from tablets displayed a diffusion-controlled mechanism. Based on the study results, formulation F7 was selected as the best formulation.

Preparation of tofacitinib sustained-release tablets using hot melt extrusion technology

This study aimed to develop a tablet that shows a drug release profile similar to the tofacitinib sustained-release tablet (Xeljanz XR®; OROS™) using hot melt extrusion technology. Tofacitinib citrate was selected as the drug. HPMCAS, HPMCP, and Kollidon VA64 were used as thermoplastic polymers to prepare a hot-melt extrudate. The extrudate was obtained from a twin screw extruder and pelletizer. The granules were compressed using a single punch press machine and then coated. TGA, DSC, XRD, FT-IR, and SEM were performed on the hot melt extrudate to understand its physicochemical properties. Dissolution tests were performed using the paddle method (USP Apparatus II). The results showed that the crystallinity state of tofacitinib changed to amorphous after the hot melt extrusion process; however, no chemical change was observed. The drug release profile was similar to that of Xeljanz XR®, which has an initial lag time owing to its OROS™ formulation; a coating process was performed to obtain a similar drug release profile. The lag time was controlled by adjusting the thickness of the coating layer. Moreover, the extrudate size and compression force during tableting did not significantly affect drug release. In conclusion, the new tofacitinib sustained-release tablet prepared using hot melt extrusion showed a drug release behavior similar to that of Xeljanz XR®.

Combined eutexia and amorphization for simultaneous enhancement of dissolution rate of triamterene and hydrochlorothiazide: Preparation of orodispersible tablets

ABSTRACT Background: Triamterene is an oral antihypertensive drug with dissolution-limited poor bioavailability. It can be used as monotherapy or in fixed dose combination with hydrochlorothiazide which also suffers from poor dissolution. Moreover, co-processing of drugs in fixed dose combination can alter their properties. Accordingly, pre-formulation studies should investigate the effect of co-processing and optimize the dissolution of drugs before and after fixed dose combination. This is expected to avoid deleterious interaction (if any) and to hasten the biopharmaceutical properties. Objective: Accordingly, the aim of this work was to optimize the dissolution rate of triamterene alone and after fixed dose combination with hydrochlorothiazide. Methodology: Triamterene was subjected to dry co-grinding with xylitol, HPMC-E5 or their combination. The effect of co-grinding with hydrochlorothiazide was also tested in absence and presence of xylitol and HPMC-E5. The products were assessed using Fourier-transform infrared (FTIR), differential scanning calorimetry, X-ray powder diffraction (XRPD), in addition to dissolution studies. Optimum formulations were fabricated as oral disintegrating tablets (ODT). Results: Co-processing of triamterene with xylitol formed eutectic system which hastened dissolution rate. HPMC-E5 resulted in partial amorphization and improved triamterene dissolution. Co-grinding with both materials combined their effects. Co-processing of triamterene with hydrochlorothiazide resulted in eutexia but the product was slowly dissolving due to aggregation. This problem was vanished in presence of HPMC-E5 and xylitol. Compression of the optimum formulation into ODT underwent fast disintegration and liberated acceptable amounts of both drugs. Conclusion: The study introduced simple co-processing with traditional excipients for development of ODT of triamterene and hydrochlorothiazide.

Herb induced liver injury by Xianling Gubao Tablets: A case assessed for causality using updated RUCAM and integrated evidence chain

ObjectiveA typical case of Xianling Gubao (XLGB) Tablets-induced liver injury was systematically studied in the clinic and the laboratory. MethodsA patient with herb-induced liver injury (HILI) and a history of taking XLGB Tablets before disease onset was engaged as the study subject, and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method (RUCAM) and the integrated evidence chain (iEC) method recommended by the Guidelines for Diagnosis and Treatment of Herb-induced Liver Injury (HILI Guidelines). ResultsClinical history, biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral, alcoholic and autoimmune liver diseases on the diagnosis. Based on an investigation of the patient’s medication history, she was suspected to have HILI caused by XLGB Tablets, as the patient was only taking an oral preparation of XLGB Tablets, and the influence of other drugs on the diagnosis was excluded. This patient with alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury. The relationship was considered “highly probable” (score of 9) using the updated RUCAM of 2016. Moreover, the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99, suggesting that the patient was consuming XLGB Tablets rather than another drug. LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug, and no chemical additions were found. Examination of the drug for pesticide residues, heavy metals, aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia. ConclusionIn summary, the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC. Therefore, this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.