In vitro evaluations of warfarin tablets available in the brazilian market

Indonesia is known with its high biodiversity. One of them is sea cucumber. Various species of sea cucumbers are found in Indonesian sea in Talaud Regency at Kabaruan Island. Identification of sea cucumbers to reveal the biodiversity of sea cucumbers in Kabaruan Island, which is almost unknown. This research was to identify six samples of sea cucumber (Holothuroidea) in Kabaruan Island based on morphology and DNA barcoding using the COI gene. The differences between each species can be seen from the morphological characteristics, the length and width of sea cucumbers, papillae, pattern and color. The results showed that there were 4 species from 6 samples, which is Holothuria leucospilota, Holothuria whitmaei, Eleutherozoa sp., and Holothuria atra. That six samples with the code A1, A2, B1, C1, and C2 have a homology level of 99%-100% with the target nucleotide sequence from GenBank. Meanwhile, the sample’s code A3 has a homology level of 90% with the Eleutheroza sp. so there is a possibility that sample A3 is a new taxa that has the highest similarity to the Eleutheroza sp. From the six samples, it was found that samples A2 and B1 had the highest level of similarity which is 100%. Meanwhile, the samples with the lowest percentage values are samples A3 and B1 and samples A2 and A3, with a percentage value of 82.75%. There were 4 species from six samples found in Kabaruan Island. There is a possibility that Sample A3 is a new species that is similar to Eleutheroza sp.

The pH and functional properties: water and oil absorption capacity, bulk density, solubility, swelling power and foaming capacity of tigernut and cowpea flour blends were determined. The flour blends were coded with the letters B, C, D, E, F, G and H for cowpea flour substitutions of 5, 10, 15, 20, 30, 40 and 50 % respectively. For comparison sample A1, A2 and A3 representing 100 % of wheat, tigernut and cowpea respectively, were also evaluated. Standard methods were used for all the analysis. pH of the flour samples varied significantly (P ≤ 0.05) from 5.60-6.23 for sample B (5 % cowpea flour substitution) and A2 (100% tiger nut flour) respectively. Water and oil absorption capacity varied significantly (P ≤ 0.05) from 1.00-2.90 ml/g and 0.39-1.38 ml/g respectively. Sample A1 (100% wheat flour) and Sample B (5% Cowpea: 95% tigernut flour) was significantly (P ≤ 0.05) the highest in water absorption capacity while sample A1 (% wheat flour) had the highest oil absorption capacity. Bulk density varied from 0.58 - 0.84 g/cm3. Although Cowpea flour (sample A3) had the highest bulk density, there was significant (P ≤ 0.05) decrease with increase in cowpea substitution. Swelling power and solubility ranged from 0.08-6.74 g/g and 8.00–67.35 % respectively. Sample A1 (% wheat flour) had significantly (P ≤ 0.05) the highest solubility and swelling power while Sample A3 (% cowpea flour) had the least. The functional properties of the tigernut-cowpea composite flour were comparable with that of the wheat flour, except for the swelling power that was significantly (P ≤ 0.05) higher for the wheat flour. The result showed that the composite tigernut-cowpea flour can be good alternative in the production of bakery products that would not require much swelling.

The evaluation of microplastics (MPs) in bottled water samples sold in the Abakaliki metropolis was investigated. The absorption peak of the infrared spectroscopy (IR) obtained were 1397, 1636, 1830, 2303, 3261, and 3749 cm-1for sample A1; 1640 cm-1, 2117 cm-1, 3268 cm-1 for A2; while A3, A4 and A5 samples were respectively: 1640 cm-1, 2120 cm-1, 3268 cm-1; 1640 cm-1, 2124 cm-1, 3268 cm-1; 1640 cm-1, 2105 cm- 1 and 3273 cm-1. The functional groups that correspond to the absorption peak of samples A1 to A5 were C=C, C=O, O-H, and an additional C-O for sample A1. Interestingly, all the studied samples were absorbed at 1640 cm-1 while other absorption peaks varied. The particle size of the sample ranged from 17.20 particle/0.75L sample A5 to 44.63 particle/0.75L sample A3. The predominant shape of the microplastic detected was granules. Microplastic pollution load index (MPPLI), micro-plastic contamination factor (MPCF), and the estimated daily intake (EDI) for both children and adults were determined. The MPCF values obtained ranged from 1.00 for sample A1 to 2.59 for sample A3 and followed the profile A5<A1<A4<A2<A3. The result for EDI for adults was less than 1 except in samples A2 and A3 which were slightly greater than 1. The EDI for children ranged from 2.06 samples A5 to 5.36 samples A3. The EDI result showed that children consume more microplastics than adults. The MPPLI was obtained to be 1.58. The microplastic abundance was calculated as 12 % for samples A1 and A5, 21 % for sample A4, 24 % for sample A2, and 31 % abundance for sample A3.

The effect of processing methods on the physicochemical, functional, anti-nutrient factors and pasting properties of Mucuna sloanei (ukpo), Brachystegia eurycoma (achi) and Daterium microcarpum (ofor) were assessed using standard methods. Flour from these seeds were produced after boiling and soaking at different time intervals. The moisture and ash contents of the three soup thickeners ranged between 5.58- 8.92% and 1.14-5.59% with sample B1 (achi boiled for 15 min) and C4 (ofor soaked for 48 h) having the lowest while sample B2 (achi boiled for 30 min) and C1 (ofor boiled for 15 min) having the highest. Crude Fat and fibre contents ranged from 2.90-10.95% and 1.30-14.39% with samples C1 and A1 (ukpo boiled for 15 min) as the highest respectively. Crude protein and carbohydrate contents of soup thickeners ranged between 9.19 -21.31% and 45.01-71.38% with samples A3 (ukpo soaked for 24 h) and B4 (achi soaked for 48 h) as the highest. Sugar and starch contents ranged from 2.61-5.04% and from 69.00-74.27% respectively with sample C4 and A4 (ukpo soaked for 48 h) as the lowest and sample A3 and B3 (Achi soaked for 24 h) as the highest. Amylose content increased with boiling and decreased with soaking which was the reverse amylopectin. Functional properties showed bulk density and dispersibility to range between 0.56-0.76 g/ml and 32.50-48-00% with sample B3 (achi soaked for 24 h) as highest in both cases. Solubility and swelling power ranged from 32.56-107.51% and from 4.61-8.72 g/g with sample A2 (ukpo boiled for 30 min) and A1 having the highest respectively. Foam capacity ranged from 2.50-29.50% with sample C2 (ofor soaked for 48 h) having the lowest and sample A1 having the highest, while the least gelation concentration of the three soup thickeners recorded 2.00% for all the treatments. Water absorption capacity ranged between 0.67-10.46 ml/g with B1 having the lowest and sample C2 having the highest. Antinutritional factors showed that phytate recorded 0.01 g/kg for all the treatments, tannin ranged from 2.22-40.71 mg/kg, oxalate between 3.40-7.90mg/100g and saponin between 2.60-9.18% with different treatments affecting the antinutrients. Free fatty acid, peroxide value, saponification and acid values increased with an increase in treatment time while iodine value decreased as processing time increased. Pasting result showed that treatment and time affected pasting properties with the highest values as peak viscosity 16429RVU, trough viscosity 9231RVU, breakdown 7858RVU, final viscosity 19977RVU and set back viscosity 13004RVU respectively. Peak time and pasting temperature ranged between 1.60-6.10 min and between 50.25-76.18°C for the different treatments. This study shows the need for appropriate treatment and time combination for better nutrient availability and detoxification of these seeds as soup thickeners.

Background: According to the guidelines for cGMP, strictly regulated procedures and quality control (QC) tests are required. However, none of the regulations by authorities suggested have β galactosidase and Annexin V/PI assays as QC tests. In this study, we aimed to demonstrate the feasibility of Annexin V and β galactosidase assays as valid cGMP compliant QC tests. Methods: Wharton’s Jelly derived mesenchymal stem cells (WJ MSCs) were isolated, characterized and screened as valid QC tests. In this study, in addition to routine QC tests, β gal assays were performed to confirm telomerase activity and Annexin V methods were used to confirm cell viability assays. Results: It was concluded that one donor (WJ MSC 3) has higher telomerase activity and it has lowest β gal activity at the same time (p<0,001). Only one donor showed significant difference in annexin V viability tests, indicating the importance of using automatic devices and Annexin V to manual tests for cell viability analysis (Muse: 92,48 ± 0,487% Flow Cytometry: 90,76 ± 1,116% p<0,01). Conclusion: With these existing data, telomerase activity and senescence levels may correlate and affect MSC quality in cell based therapy. In order to determine the viability values by adding Annexin V based automated methods could give more guaranteed results. Key words: Good Manufacturing Practice, SA b galactosidase, cell senescence, telomerase activity, Annexin V, cell based medicinal products. DOI: 10.7176/JSTR/6-12-07

The objective of this study was to assess how solubility and dissolution profile comparisons under different pH conditions can be used to predict gastric pH-mediated drug-drug interaction (DDI) potential. We collected information for new molecular entities (NMEs) approved from 2003 to 2019 by the U.S. Food and Drug Administration (FDA) that had dedicated clinical DDI studies with acid-reducing agents (ARAs). Among these, 67 NMEs with solubility under different pHs and dissolution profiles generated in pH 1.2, 4.5, and 6.8 aqueous media were included for analysis. Similarity factor (f2) was used to compare dissolution profiles at different pHs for pH-mediated DDI prediction (e.g., f2<50 predicts positive DDI). Prediction accuracy was calculated based on the outcome comparison between predicted and observed DDIs. Based on dissolution profile comparisons and observed DDI data, weak base drugs (WBDs) (n = 49) showed 72.5% prediction accuracy under the fasted conditions, and 66.7% prediction accuracy under fed conditions. While using solubility and clinical dose for prediction, the prediction accuracy was 80% under fasted conditions and 66.7% under fed conditions, respectively. Comparison of dissolution profiles generated at pH 1.2, 4.5, and 6.8 can be used to predict gastric pH-mediated DDI potential for WBDs. It demonstrated comparable prediction accuracy under both fasted and fed conditions when compared to the prediction using solubility and clinical dose. Furthermore, dissolution profile comparison could add an additional understanding of possible impact of pH change on the release behavior of the drug product. Graphical abstract.

Tablet splitting is a well-established medical practice in clinical settings for multiple reasons, including cost savings and ease of swallowing. However, it does not necessarily result in weight-uniform half tablets. To (a) investigate the effect of tablet characteristics on weight and content uniformity of half tablets, resulting from splitting 16 commonly used medications in the outpatient setting and (b) provide recommendations for safe tablet-splitting prescribing practices. Ten random tablets from each of the selected medications were weighed and split by 5 volunteers (2 men and 3 women aged 25-44 years) using a knife. The selected medications were mirtazapine 30 mg, bromazepam 3 mg, oxcarbazepin 150 mg, sertraline 50 mg, carvedilol 25 mg, bisoprolol fumarate 10 mg, losartan 50 mg, digoxin 0.25 mg, amiodarone HCl 200 mg, metformin HCl 1,000 mg, glimepiride 4 mg, montelukast 10 mg, ibuprofen 600 mg, celecoxib 200 mg, meloxicam 15 mg, and sildenafil citrate 50 mg. The resulting half tablets were evaluated for weight and drug content uniformity in accordance with proxy United States Pharmacopeia (USP) specification (95%-105% for digoxin and 90%-110% for the other 15 drugs). Weight and drug content uniformity were assessed by comparing weight or drug content of the half tablets with one-half of the mean weight or drug content for all whole tablets in the sample. The percentages by which the weight and drug content of each whole tablet or half tablet differed from sample mean values were calculated. Other relevant physical characteristics of the 16 products were measured. A total of 52 of 320 half tablets (16.2%) and 48 of 320 half tablets (15.0%) fell outside of the proxy USP specification for weight and drug content, respectively. Bromazepam, carvedilol, bisoprolol, losartan, digoxin, and meloxicam half tablets failed the weight and content uniformity test; however, the half tablets for the rest of the medications passed the test. Mean percent weight loss after splitting was less than 1.5% for all drugs. Bromazepam, carvedilol, and digoxin showed the highest powdering loss during the tablet-splitting process. Tablet splitting could be safer and easier when drug- and patient-specific criteria have been met. Tablet size, shape, and hardness may also play a role in the decision to split a tablet or not. Tablets containing drugs with a wide therapeutic index and long half-life might be more suitable candidates for division. Dose variation exceeded a proxy USP specification for more than one-third of sampled half tablets of bromazepam, carvedilol, bisoprolol, and digoxin. Drug content variation in half tablets appeared to be attributed to weight variation due to fragment or powder loss during the splitting process.

Background: Tablet splitting is a common practice for multiple reasons including cost savings; however, it does not necessarily result in weight-uniform half-tablets. Objectives: To determine weight uniformity of half-tablets resulting from splitting 4 products available in the Jordanian market and investigate the effect of tablet characteristics on weight uniformity of half-tablets. Methods: Ten random tablets each of warfarin 5 mg, digoxin 0.25 mg, phenobarbital 30 mg, and prednisolone 5 mg were weighed and split by 6 PharmD students using a knife. The resulting half-tablets were weighed and evaluated for weight uniformity. Other relevant physical characteristics of the 4 products were measured. Results: The average tablet hardness of the sampled tablets ranged from 40.3 N to 68.9 N. Digoxin, phenobarbital, and prednisolone half-tablets failed the weight uniformity test; however, warfarin half-tablets passed. Digoxin, warfarin, and phenobarbital tablets had a score line and warfarin tablets had the deepest score line of 0.81 mm. Conclusion: Splitting warfarin tablets produces weight-uniform half-tablets that may possibly be attributed to the hardness and the presence of a deep score line. Digoxin, phenobarbital, and prednisolone tablet splitting produces highly weight variable half-tablets. This can be of clinical significance in the case of the narrow therapeutic index medication digoxin.

Radiopharmaceuticals are widely used for the diagnosis and therapy of disease. Similarly to conventional drugs, radiopharmaceuticals are subjected to quality control (QC) tests before administration to patients. Nevertheless, due to the presence of radionuclides, radiopharmaceuticals undergo additional QC testing. High quality diagnostic radiopharmaceuticals are required for accurate diagnosis and administration of optimal treatment and dose to patients. High quality therapeutic radiopharmaceuticals are necessary to minimize extra radiation burden to patients. To obtain high purity radiopharmaceuticals, it is imperative to guarantee quality at every step of the entire process, from production to release. This chapter describes (a) good manufacturing practices in radiopharmaceuticals, (b) QC tests – physicochemical and biological – and (c) practical considerations in quality assurance of radiopharmaceuticals.

In vitro dissolution testing is one of the most important tools for characterizing the performance of oral solid dosage forms. In order to demonstrate similarity between test and reference product, comparative dissolution profiles are performed. Selection of a suitable method for comparison of the dissolution profile of the reference product and the test product is of great importance especially in the case of biowaivers when similarity assessment is based on the in vitro data only. Various approaches have been developed for the comparison of dissolution profiles, however the usage of the f2 similarity factor is widely accepted due to its simplicity. When the conditions for using f2 similarity factor are not fulfilled due to high variable dissolution profiles, f2 bootstrap method is then recommended. The focus of this study is to see whether it is benefitial f2 bootstrap analysis to replace the usage of simple f2 for comparison of dissolution profiles that fulfill the prerequisites for using the f2 method in cases when borderline f2 results are obtained. Keywords: Bootstrap analysis, comparative dissolution profiles, similarity factor f2

The drinking water sources in Abakaliki, Nigeria were investigated for PFAS concentration. PFAS has been known for its bioaccumulation in the food chain, causing a detrimental health effect to humans when contaminated food is ingested. 13 targeted PFAS were analyzed using a Gas Chromatography-Mass Spectrometry (GC-MS) technique. This method allowed for the identification and quantification of specific PFAS compounds present in the sample. Perfluorohexanoate (PFHX1), N-methylperfluorooctanesulfonamide (MeFOSA), and N-ethylperfluorooctanesulfonamides (ETFOSA) were the only perfluoroakyl substances found others were fluorotelomers which are polyfluoroalkyl substance and there were the predominant PFAS obtained in this study. The mean sum of the targeted PFAS (⅀PFAS) across all the samples analyzed ranged from 0.22±0.06 mg/L (sample A3) to 7.20±1.82 mg/L (sample C4). The mean value of the PFAS obtained in samples A1 to A5 ranged from 0.22±0.06 mg/L (samples A3) to 0.59±0.12 mg/L (sample A1) while the mean values of samples B1-B5, C1-C5, and D1-D5 ranged from 0.35±0.08 mg/L (B1) to 1.14±0.21 mg/L (B5), 0.64±0.04 mg/L (C3) to7.20±1.82 mg/L (C4) and 0.63±0.04 mg/L (D1) to 3.61±1.08 mg/L (D4) respectively. PFAS are contaminants of emerging concern whose toxicity is of environmental and health concern. However, the detection of PFAS in water is gradually decreasing because of the restriction of PFAS and its industrial applications, which result from environmental and health-associated problems.

This paper is focused on exploring and utilizing the acoustic emission and its behaviour during surface roughness measurement. Surface quality or coating properties significantly affect the reliability and durability of operations. Three samples were selected for an experiment to demonstrate the possibility of measuring the roughness of surface textures by means of acoustic emission method (AE). These samples were made of the following materials: sample A2 – EN 54SiCr6 steel formed in water, austenitized at 850 °C for 20 minutes, sample A3 – non-heat-treated spheroidal graphite cast iron, and sample B5 – abrasion resistant austenitic manganese steel. The surfaces were subjected to the same surface treatments (roughness Ra = 1.6–3.2 μm) and measured under the same conditions. All possible measurements were measured on both x- and y-axes. Final results are presented graphically. The measured AE values showed a visible effect in the AE signals due to the lack of surface roughness.

Lamotrigine (L) is a known drug in the treatment of epilepsy and bipolar disorder. Due to its unique structure and functionalities, L is able to form both salts and cocrystals. The present study reports ionic, neutral, and hybrid crystalline forms of L with improved material properties and modified drug release rates. Novel forms of L with cinnamic acid (CA), ferulic acid (FRA), salicylic acid (SAC), and vanillin (VN) were successfully prepared and characterized using single crystal XRD, SEM, FT–IR, DSC, TGA, and powder XRD. LCA and LVN crystallized in P21/c space group, whereas LSAC crystallized in P1 space group. Pseudo-quadruple hydrogen bond with R42 (16) graph set notation were observed in all three crystal structures of L. The characteristic FT–IR stretching peaks at 3326.53, 3341.53, and 3340.65 cm–1 corresponding to N+–H bond were observed in LCA, LFRA, and LSAC. Comparison of dissolution profiles using similarity factor (f2) analysis revealed that the dissolution profiles of LCA, LFRA, and LVN w...

Tablet splitting is widely practiced worldwide. Several studies have considered weight variation of split tablets as a mean of estimating drug content uniformity but the analysis of their drug content and physical factors that may affect splitting are limited. The aim of this study is to evaluate the impact of manufacturing parameters and splitting on content and weight uniformity of atenolol tablets. Atenolol tablets (100 and 50 mg) were prepared under the same manufacturing conditions and using the same excipients. The obtained tablets were checked for hardness, weight, and disintegration. The weight and the content of the two strength atenolol tablets after splitting into two halves were evaluated. Atenolol tablets (100 mg) showed higher values of hardness, disintegration time and diameter than atenolol tablets (50 mg). Atenolol tablets (100 mg) passed both weight and content uniformity while atenolol tablets (50 mg) failed these tests. Half tablet weight appears to be directly correlated with its drug content. Manufacturers should investigate physical factors such as tablet hardness, diameter, and disintegration time that may play an important role in achieving both weight and content uniformity in the resultant tablet halves.

To describe the properties of the similarity factor (f2) as a measure for assessing the similarity of two dissolution profiles. Discuss the statistical properties of the estimate based on sample means. The f2 metrics and the decision rule is evaluated using examples of dissolution profiles. The confidence interval is calculated using bootstrapping method. The bias of the estimate using sample mean dissolution is evaluated. 1. f2 values were found to be sensitive to number of sample points, after the dissolution plateau has been reached. 2. The statistical evaluation of f2 could be made using 90% confidence interval approach. 3. The statistical distribution of f2 metrics could be simulated using 'Bootstrap' method. A relatively robust distribution could be obtained after more than 500 'Bootstraps'. 4. A statistical 'bias correction' was found to reduce the bias. The similarity factor f2 is a simple measure for the comparison of two dissolution profiles. But the commonly used similarity factor estimate f2 is a biased and conservative estimate of f2. The bootstrap approach is a useful tool to simulate the confidence interval.