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Molecules (Basel, Switzerland) Apr 2022The assessment of active pharmaceutical ingredient (API) particle size and morphology is of great importance for the pharmaceutical industry since it is expected to...
The assessment of active pharmaceutical ingredient (API) particle size and morphology is of great importance for the pharmaceutical industry since it is expected to significantly affect physicochemical properties. However, very few methods are published for the determination of API morphology and particle size of film-coated (FC) tablets. In the current study we provide a methodology for the measurement of API particle size and morphology which could be applied in several final products. Bismuth Oxide 120 mg FC Tabs were used for our method development, which contain bismuth oxide (as tripotassium dicitratobismuthate (bismuth subcitrate)) as the active substance. The sample preparation consists of partial excipient dissolution in different solvents. Following this procedure, the API particles were successfully extracted from the granules. Particle size and morphology identification in Bismuth Oxide 120 mg FC Tabs was conducted using micro-Raman mapping spectroscopy and ImageJ software. The proposed methodology was repeated for the raw API material and against a reference listed drug (RLD) for comparative purposes. The API particle size was found to have decreased compared to the raw API, while the API morphology was also affected from the formulation manufacturing process. Comparison with the RLD product also revealed differences, mainly in the API particle size and secondarily in the crystal morphology.
Topics: Bismuth; Excipients; Particle Size; Tablets
PubMed: 35458800
DOI: 10.3390/molecules27082602 -
The Journal of International Medical... Oct 2023We performed a meta-analysis to determine whether the addition of probiotics to the bismuth quadruple therapy (BQT) for would improve the incidence of eradication and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We performed a meta-analysis to determine whether the addition of probiotics to the bismuth quadruple therapy (BQT) for would improve the incidence of eradication and reduce that of side effects.
METHODS
Randomized controlled trials matching the inclusion criteria were collected from PubMed, Embase, Web of Science, and The Cochrane Central Register of Controlled Trials. A Mantel-Haenszel random-effects model was used to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for the incidences of eradication rate, side effects as a whole, diarrhea, and other side effects.
RESULTS
Ten studies were selected for inclusion in the meta-analysis. The pooled RRs for the eradication rates in intention-to-treat and per-protocol analyses of the probiotic group . the control group were 1.07 (95% CI: 1.02-1.11) and 1.04 (95% CI: 1.00-1.07), respectively. Probiotic supplementation reduced the incidences of side effects (RR 0.58, 95% CI: 0.37-0.91), diarrhea (RR 0.41, 95% CI: 0.25-0.67), and bitter taste (RR 0.63, 95% CI: 0.40-0.99).
CONCLUSIONS
The results of this meta-analysis support the use of probiotics in combination with BQT in the clinical management of patients with infection.
Topics: Humans; Helicobacter Infections; Bismuth; Helicobacter pylori; Anti-Bacterial Agents; Drug Therapy, Combination; Dietary Supplements; Probiotics; Diarrhea; Treatment Outcome
PubMed: 37848344
DOI: 10.1177/03000605231203841 -
Current Gastroenterology Reports Jul 2016Helicobacter pylori infects about 50 % of the world's population, causing at a minimum chronic gastritis. A subset of infected patients will ultimately develop gastric... (Review)
Review
Helicobacter pylori infects about 50 % of the world's population, causing at a minimum chronic gastritis. A subset of infected patients will ultimately develop gastric or duodenal ulcer disease, gastric adenocarcinoma, or MALT (mucosa-associated lymphoid tissue) lymphoma. Eradication of H. pylori requires complex regimens that include acid suppression and multiple antibiotics. The efficacy of treatment using what were once considered standard regimens have declined in recent years, mainly due to widespread development of antibiotic resistance. Addition of bismuth to standard triple therapy regimens, use of alternate antibiotics, or development of alternative regimens using known therapies in novel combinations have improved treatment efficacy in specific populations, but overall success of eradication remains less than ideal. Novel regimens under investigation either in vivo or in vitro, involving increased acid suppression ideally with fewer antibiotics or development of non-antibiotic treatment targets, show promise for future therapy.
Topics: Anti-Bacterial Agents; Bismuth; Chronic Disease; Drug Resistance, Bacterial; Drug Therapy, Combination; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pump Inhibitors
PubMed: 27177639
DOI: 10.1007/s11894-016-0509-x -
Microbiology Spectrum Feb 2022Antibiotic resistance has caused a serious threat to public health and human safety. Recently, the emergence of novel resistance gene (X4) and its variants threatens the...
Antibiotic resistance has caused a serious threat to public health and human safety. Recently, the emergence of novel resistance gene (X4) and its variants threatens the clinical utility of tigecycline, one of the last-line antibiotics for multidrug-resistant (MDR) bacterial infections. It is highly promising to develop effective antibiotic adjuvants to restore the clinical efficacy of existing drugs and extend their life spans. Metal compounds, such as silver, have been widely used as potential antimicrobial agents for decades. However, the potentiating effect of metallo-agents on the existing antibiotics is not fully understood. Here, we found that five bismuth drugs, especially bismuth nitrate [Bi(NO)], commonly used in clinical treatment of stomach-associated diseases, effectively boost the antibacterial activity of tigecycline against (X)-positive bacteria by inhibiting the enzymatic activity of Tet(X) protein. Furthermore, the combination of Bi(NO) and tigecycline prevents the development of higher-level resistance in Tet(X)-expressing Gram-negative bacteria. Using molecular docking and dynamics simulation assays, we revealed that Bi(NO) can competitively bind to the active center of Tet(X4) protein, while the bismuth atom targets the Tet(X4) protein in a noncompetitive manner and changes the structure of the primary binding pocket. These two mechanisms of action both antagonize the enzymatic activity of Tet(X4) resistance protein on tigecycline. Collectively, these findings indicate the high potential of bismuth drugs as novel Tet(X) inhibitors to treat (X4)-positive bacteria-associated infections in combination with tigecycline. Recently, high-level tigecycline resistance mediated by (X4) and its variants represents a serious challenge for global public health. Antibiotic adjuvant strategy that enhances the activity of the existing antibiotics by using nonantibiotic drugs offers a distinct approach to combat the antibiotic resistance crisis. In this study, we found that bismuth drugs involve bismuth nitrate, a compound previously approved for treatment of stomach-associated diseases, remarkably potentiates tigecycline activity against (X)-positive bacteria. Mechanistic studies showed that bismuth drugs effectively suppress the enzymatic activity of Tet(X) resistance protein. Specifically, bismuth nitrate targets the active center of Tet(X4) protein, while bismuth binds to the resistance protein in a noncompetitive manner. Our data open up a new horizon for the treatment of infections caused by (X)-bearing superbugs.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Bismuth; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Molecular Docking Simulation; Tigecycline
PubMed: 35138168
DOI: 10.1128/spectrum.01578-21 -
Digestive Diseases and Sciences Jul 2021A large number of studies have evaluated the pharmacology, safety, and/or efficacy of bismuth subsalicylate for the relief of common gastrointestinal symptoms, diarrhea... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A large number of studies have evaluated the pharmacology, safety, and/or efficacy of bismuth subsalicylate for the relief of common gastrointestinal symptoms, diarrhea and vomiting due to acute gastroenteritis. In addition, short-term (48 h) medication with bismuth subsalicylate is known to be effective against infectious gastroenteritis such as travelers' diarrhea.
AIMS
Previous studies have documented the bacteriostatic/bactericidal effects of bismuth subsalicylate against a variety of pathogenic gastrointestinal bacteria. However, meta-analyses of the clinical efficacy of bismuth subsalicylate for both prevention and treatment of travelers' diarrhea have not yet been published.
METHODS
A total of 14 clinical studies (from 1970s to 2007) comprised the core data used in this assessment of efficacy of bismuth subsalicylate against infectious (including travelers') diarrhea. These studies allowed for statistical meta-analyses regarding prevention (three travelers' diarrhea studies) and treatment of infectious diarrhea (11 studies [five travelers' diarrhea]).
RESULTS
The results show that subjects treated with bismuth subsalicylate for up to 21 days have 3.5 times greater odds of preventing travelers' diarrhea compared with placebo (95% CI 2.1, 5.9; p < 0.001). In addition, subjects with infectious diarrhea treated with bismuth subsalicylate had 3.7 times greater odds of diarrhea relief (recorded on diaries as subjective symptomatic improvement) compared to those receiving placebo (95% CI 2.1, 6.3; p < 0.001).
CONCLUSIONS
This systematic review and meta-analysis suggests that bismuth subsalicylate can be beneficial for those at risk or affected by food and waterborne diarrheal disease such as traveler's (infectious) diarrhea, and may decrease the risk of inappropriate antibiotic utilization.
Topics: Bismuth; Communicable Diseases; Diarrhea; Humans; Organometallic Compounds; Salicylates; Travel
PubMed: 32772204
DOI: 10.1007/s10620-020-06509-7 -
Environmental Science & Technology Mar 2022The use of bismuth in the society has steadily increased during the last decades, both as a substitute for lead in hunting ammunition and various metallurgical...
The use of bismuth in the society has steadily increased during the last decades, both as a substitute for lead in hunting ammunition and various metallurgical applications, as well as in a range of consumer products. At the same time, the environmental behavior of bismuth is largely unknown. Here, the binding of bismuth(III) to organic soil material was investigated using extended X-ray absorption spectroscopy (EXAFS) and batch experiments. Moreover, the capacity of suwannee river fulvic acid (SRFA) to enhance the solubility of metallic bismuth was studied in a long-term (2 years) equilibration experiment. Bismuth(III) formed exceptionally strong complexes with the organic soil material, where >99% of the added bismuth(III) was bound by the solid phase, even at pH 1.2. EXAFS data suggest that bismuth(III) was bound to soil organic matter as a dimeric Bi complex where one carboxylate bridges two Bi ions, resulting in a unique structural stability. The strong binding to natural organic matter was verified for SRFA, dissolving 16.5 mmol Bi per gram carbon, which largely exceeds the carboxylic acid group density of this compound. Our study shows that bismuth(III) will most likely be associated with natural organic matter in soils, sediments, and waters.
Topics: Bismuth; Rivers; Soil; Solubility; X-Ray Absorption Spectroscopy
PubMed: 35129969
DOI: 10.1021/acs.est.1c06982 -
Current Opinion in Chemical Biology Apr 2012Bismuth has been used in medicine for over two centuries for the treatment of various diseases, in particular for gastrointestinal disorders, owing to its antimicrobial... (Review)
Review
Bismuth has been used in medicine for over two centuries for the treatment of various diseases, in particular for gastrointestinal disorders, owing to its antimicrobial activity. Recent structural characterization of bismuth drugs provides an insight into assembly and pharmacokinetic pathway of the drugs. Mining potential protein targets inside the pathogen via metallomic/metalloproteomic approach and further characterization on the interactions of bismuth drugs with these targets laid foundation in understanding the mechanism of action of bismuth drugs. Such studies would be beneficial in rational design of new potential drugs.
Topics: Bismuth; Drug Design; Humans; Organic Chemistry Phenomena; Proteins
PubMed: 22322154
DOI: 10.1016/j.cbpa.2012.01.006 -
Medicine Dec 2021The aim of this study was to evaluate the efficacy and safety of bismuth pectin capsules and bismuth pectin granules in the first-line quadruple treatment of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The aim of this study was to evaluate the efficacy and safety of bismuth pectin capsules and bismuth pectin granules in the first-line quadruple treatment of Helicobacter pylori (H. pylori).
METHODS
This study was a multicenter, randomized, open-labelled controlled clinical trial. Patients with a H. pylori infection were randomized into 4 groups (1:1:1:1) and treated with a 14-day bismuth-containing quadruple therapy. The 4 groups received either bismuth potassium citrate capsules (220 mg), colloidal bismuth pectin capsules (200 mg), bismuth pectin granules (150 mg), or bismuth pectin granules (300 mg). The primary outcome was the eradication rate of H. pylori. The secondary outcomes included symptom improvement, patient compliance, and incidence of adverse events. This study was registered at ClinicalTrials.gov (NCT04209933).
RESULTS
A total of 240 patients were included in this study, and 211 patients completed the follow-up. An intention-to-treat analysis showed that the H. pylori eradication rates of the 4 groups were 73.3%, 76.7%, 75.0%, and 71.7%, respectively. The per-protocol analysis showed that the H. pylori eradication rates of the 4 groups were 86.3%, 82.1%, 83.3%, and 86.0%. There was no significant difference among the 4 groups in the H. pylori eradication rate (P > .05). There were also no significant differences in the symptom improvement rate, overall adverse reaction rate, or patient compliance among the 4 groups.
CONCLUSIONS
Bismuth pectin capsules and bismuth pectin granules had similar efficacy and safety for H. pylori eradication compared to bismuth potassium citrate. These data suggest that bismuth pectin can be an alternative to bismuth potassium citrate to eradicate H. pylori when using bismuth-containing quadruple therapy.
Topics: Adult; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Bismuth; Capsules; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Potassium Citrate; Proton Pump Inhibitors; Treatment Outcome
PubMed: 34918639
DOI: 10.1097/MD.0000000000027923 -
Journal of Nanobiotechnology Aug 2020Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles...
BACKGROUNDS
Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming.
METHODS
In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent.
RESULTS
The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility.
CONCLUSIONS
This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.
Topics: Animals; Bismuth; Contrast Media; Iohexol; Kidney; Metal Nanoparticles; Mice; Pentetic Acid; Tissue Distribution; Tomography, X-Ray Computed; Whole Body Imaging
PubMed: 32762751
DOI: 10.1186/s12951-020-00669-4 -
Asian Journal of Surgery Oct 2023Evidence regarding the optical surgical extent for Bismuth type I/II HCCA is lacking. we aims to evaluate the optimal surgical methods for Bismuth type I/II HCCA.... (Meta-Analysis)
Meta-Analysis Review
Evidence regarding the optical surgical extent for Bismuth type I/II HCCA is lacking. we aims to evaluate the optimal surgical methods for Bismuth type I/II HCCA. Studies comparing bile duct resection (BDR) and BDR combined with liver resection (BDR + LR) for all types of HCCA patients were searched for analyses, and 14 studies were finally included. The main outcomes were the R0 resection rate and overall survival (OS). For all types of HCCA patents, BDR + LR resulted with higher R0 resection rates when comparing with BDR only (RR = 0.70, 95%CI, 0.63-0.78), and patients with R0 resections had eight times longer median survival and more long-time survival outcomes (3 and 5 year OS) comparing to those with non-R0 resections. Bismuth I/II HCCA patients also showed longer median survival and 3-year OS after R0 resections (P = 0.04). Moreover, there was no significant difference in 3-year OS between BDR and BDR + LR (P = 0.89) and we additionally found BDR resulted in less mortality or morbidity rates. In Europe and US, they resulted the R0 resection rates could be comparable between BDR and BDR + LR (P = 0.18), and Bismuth type I HCCA accounted for 75.8%, while in Asia, BDR + LR still resulted with higher R0 resection rates (P < 0.0001) and the Bismuth type I HCCA accounted for only 40.3%. The surgical approaches may not directly impact patient prognosis, patients with R0 resections are usually associated with improved survival outcomes; for selected Bismuth type I/II HCCA, BDR may be an acceptable option with regard to lower morbidity and comparable R0 resection rate comparing with BDR + LR.
Topics: Humans; Klatskin Tumor; Cholangiocarcinoma; Bismuth; Bile Duct Neoplasms; Hepatectomy; Retrospective Studies; Bile Ducts, Intrahepatic; Treatment Outcome
PubMed: 36586821
DOI: 10.1016/j.asjsur.2022.12.043