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F1000Research 2023Enteric coating films in acidic labile tablets protect the drug molecule from the acidic environment of the stomach. However, variations in the excipients used in the...
Enteric coating films in acidic labile tablets protect the drug molecule from the acidic environment of the stomach. However, variations in the excipients used in the coating formulation may affect their ability to provide adequate protection. This study is the first to investigate the potential effects of coating materials on the protective functionality of enteric coating films for pantoprazole (PNZ) generic tablets after their recall from the market. A comparative analysis was conducted between generic and branded PNZ products, using pure drug powder for identification. The release of the drug was evaluated in different pH media. The study also utilized various analytical and thermal techniques, including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and confocal Raman microscopy. The assessment results revealed significant variations in the release profile for the generic product in acidic media at 120 min. DSC and TGA thermal profile analyses showed slight variation between the two products. XRD analysis exhibited a noticeable difference in peak intensity for the generic sample, while SEM revealed smaller particle sizes in the generic product. The obtained spectra profile for the generic product displayed significant variation in peaks and band intensity, possibly due to impurities. These findings suggest that the excipients used in the enteric coating film of the generic product may have affected its protective functionality, leading to premature drug release in acidic media. Additionally, the presence of polysorbate 80 (P-80) in the brand product might improve the properties of the enteric coating film due to its multi-functionality. : In conclusion, the excipients used in the brand product demonstrated superior functionality in effectively protecting the drug molecule from acidic media through the enteric coating film, as compared to the generic version.
Topics: Pantoprazole; Drug Liberation; Excipients; Solubility; Tablets; Stomach
PubMed: 38596002
DOI: 10.12688/f1000research.140607.1 -
Cureus Apr 2024Spontaneous esophageal rupture is an uncommon medical phenomenon that involves a sudden increase in intraesophageal pressure with negative intrathoracic pressure. Here,...
Spontaneous esophageal rupture is an uncommon medical phenomenon that involves a sudden increase in intraesophageal pressure with negative intrathoracic pressure. Here, a 21-year-old female with no history of medical illness was admitted to our accident and emergency department with a one-day history of sudden retrosternal chest pain with other symptoms. There was no foreign body ingestion, vomiting, fever, cough, trauma, or recent procedures. Physical examination revealed a soft abdomen with epigastric tenderness and normal respiratory and cardiovascular examinations. The patient underwent a chest X-ray and a computed tomography scan of the neck and chest, which revealed retropharyngeal air extending to the mediastinum with anterior chest surgical emphysema. Oesophago-gastro-duodenoscopy revealed mild gastritis with no evidence of foreign body or esophagus injury. The patient was prescribed paracetamol, pantoprazole, and clindamycin. On follow-up, the patient was doing well with no active complaints. Conservative management of spontaneous esophageal rupture can result in good clinical outcomes with no requirement for additional interventions.
PubMed: 38586228
DOI: 10.7759/cureus.57578 -
Gastroenterology Apr 2024High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to...
Comparison of Vonoprazan vs Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial.
BACKGROUND & AIMS
High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis.
METHODS
A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3- and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety.
RESULTS
Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference, -3.3; 95% confidence interval, -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P < .001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups.
CONCLUSION
In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).
PubMed: 38582271
DOI: 10.1053/j.gastro.2024.03.036 -
MethodsX Jun 2024Green analytical approaches are employed for the determination of active pharmaceutical ingredients, in conjunction with their impurities. Smart chemometric...
Greenness-sustainability metrics for assessment smart-chemometric spectrophotometric strategy for evaluation of the combination of six gastric proton-pump inhibitors with two selected impurities.
Green analytical approaches are employed for the determination of active pharmaceutical ingredients, in conjunction with their impurities. Smart chemometric spectrophotometric techniques, including orthogonal partial least square (OPLS), variable selection such as genetic algorithm (GA-OPLS), and interval selection (i-OPLS), were utilized. These chemometric models were implemented for assessing six proton-pump inhibitors Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole, Rabeprazole, and Dexlansoprazole along with two selected official impurities, namely 4-Desmethoxy omeprazole impurity and Rabeprazole-impurity B. Experimental design was implemented to separate impurities, in the process of multivariate calibration, a five-level eight-factor calibration design consisting of 25 samples was selected. This design was deliberately selected to guarantee that the components were mutually orthogonal to assess the model's performance and reliability, a separate validation set of 15 samples was constructed. The best-performing of the proposed techniques were identified by considering the least favorable values of the Correlation Coefficient (R ≥ 0.9995), the Root Mean Square Error of Prediction (RMSEP) values between (0.0102-0.5622), and the Relative Error of Prediction (REP) values between (0.2961-1.1917). The proposed and reported methods' greenness-sustainability was quantitatively evaluated, and a comparative study of the greenness profile was established through a spider chart, the National Environmental Method Index tool, advanced and modified NEMI along with the Hexagon tool, and the whiteness qualities of the presented approaches were assessed by implementing the recently adopted Red-Green-Blue paradigm and White Analytical Chemistry tool. These approaches are well-suited for use in quality control laboratories due to their observed acceptance, long-term sustainability, simplicity, and affordability.
PubMed: 38577411
DOI: 10.1016/j.mex.2024.102670 -
Contemporary Clinical Trials... Jun 2024Ascertainment of the severity of the primary outcome of upper gastrointestinal (GI) bleeding is integral to stress ulcer prophylaxis trials. This protocol outlines the...
BACKGROUND
Ascertainment of the severity of the primary outcome of upper gastrointestinal (GI) bleeding is integral to stress ulcer prophylaxis trials. This protocol outlines the adjudication process for GI bleeding events in an international trial comparing pantoprazole to placebo in critically ill patients (REVISE: Re-Evaluating the Inhibition of Stress Erosions). The primary objective of the adjudication process is to assess episodes submitted by participating sites to determine which fulfil the definition of the primary efficacy outcome of clinically important upper GI bleeding. Secondary objectives are to categorize the bleeding severity if deemed not clinically important, and adjudicate the bleeding site, timing, investigations, and treatments.
METHODS
Research coordinators follow patients daily for any suspected clinically important upper GI bleeding, and submit case report forms, doctors' and nurses' notes, laboratory, imaging, and procedural reports to the methods center. An international central adjudication committee reflecting diverse specialty backgrounds conducted an initial calibration exercise to delineate the scope of the adjudication process, review components of the definition, and agree on how each criterion will be considered fulfilled. Henceforth, bleeding events will be stratified by study drug, and randomly assigned to adjudicator pairs (blinded to treatment allocation, and study center).
RESULTS
Crude agreement, chance-corrected agreement, or chance-independent agreement if data have a skewed distribution will be calculated.
CONCLUSIONS
Focusing on consistency and accuracy, central independent blinded duplicate adjudication of suspected clinically important upper GI bleeding events will determine which events fulfil the definition of the primary efficacy outcome for this stress ulcer prophylaxis trial.
REGISTRATION
NCT03374800 (REVISE: Re-Evaluating the Inhibition of Stress Erosions).
PubMed: 38559746
DOI: 10.1016/j.conctc.2024.101284 -
Cureus Feb 2024Sjögren's syndrome is a chronic, inflammatory autoimmune disorder characterized by lymphocyte infiltration of the exocrine glands. Notably, the rehabilitation of...
Sjögren's syndrome is a chronic, inflammatory autoimmune disorder characterized by lymphocyte infiltration of the exocrine glands. Notably, the rehabilitation of partially edentulous patients with Sjögren's syndrome is limited by the scarce availability of studies that could inform therapeutic modalities and potential challenges during clinical procedures. This case report aimed to present the oral rehabilitation of a patient with Sjögren's syndrome who received fixed partial dentures (FPDs). A 28-year-old female patient sought treatment to restore her missing teeth. She was diagnosed with Sjögren's syndrome by a rheumatologist adhering to the revised version of the European criteria proposed by the American-European Consensus Group and was on a medication regimen including prednisolone, hydroxychloroquine, pantoprazole, pilocarpine, and tear substitutes to manage her condition. The final treatment plan consisted of extractions, management of gingivitis, post-and-core restorations, and a 2 mm vertical dimension increase with the placement of 15 porcelain-fused-to-metal (PFM) crowns and 4 short-span bridges. The patient underwent regular clinical and radiographic evaluations every 3 months since June 2020. Throughout this period, the fixed prostheses, teeth, and periodontal tissues demonstrated remarkable stability and exhibited no complications. This three-year case study provides evidence that meticulous planning and clinical execution can facilitate successful oral rehabilitation in young edentulous patients with Sjögren's syndrome. Tooth-supported fixed prostheses can effectively restore oral function and aesthetic appeal in these individuals, provided they undergo more frequent dental examinations than the general population and maintain a cooperative attitude throughout the treatment process.
PubMed: 38558652
DOI: 10.7759/cureus.55148 -
Frontiers in Pharmacology 2024The development of resistance to carbapenems in due to the production of metallo-β-lactamases (MBLs) is a critical public health problem because carbapenems are the...
The development of resistance to carbapenems in due to the production of metallo-β-lactamases (MBLs) is a critical public health problem because carbapenems are the last-resort drugs used for treating severe infections of extended-spectrum β-lactamases (ESBLs) producing . Restoring the activity of carbapenems by the inhibition of metallo-β-lactamases is a valuable approach to combat carbapenem resistance. In this study, two well-characterized clinical multidrug and carbapenem-resistant isolates were used. The sub-inhibitory concentrations of pantoprazole and the well-reported metallo-β-lactamase inhibitor captopril inhibited the hydrolytic activities of metallo-β-lactamases, with pantoprazole having more inhibiting activities. Both drugs, when used in combination with meropenem, exhibited synergistic activities. Pantoprazole could also downregulate the expression of the metallo-β-lactamase genes and . A docking study revealed that pantoprazole could bind to and chelate zinc ions of New Delhi and Verona integron-encoded MBL (VIM) enzymes with higher affinity than the control drug captopril and with comparable affinity to the natural ligand meropenem, indicating the significant inhibitory activity of pantoprazole against metallo-β-lactamases. In conclusion, pantoprazole can be used in combination with meropenem as a new strategy for treating serious infections caused by metallo-β-lactamases producing .
PubMed: 38533260
DOI: 10.3389/fphar.2024.1366459 -
The Indian Journal of Medical Research Feb 2024Irrational prescribing practices have major consequences on patient safety and also increase the economic burden. Real-life examples of impact of irrational prescription... (Observational Study)
Observational Study
BACKGROUND OBJECTIVES
Irrational prescribing practices have major consequences on patient safety and also increase the economic burden. Real-life examples of impact of irrational prescription have potential to improve prescribing practices. In this context, the present study aimed to capture and evaluate the prevalence of deviations from treatment guidelines in the prescriptions, potential consequence/s of the deviations and corrective actions recommended by clinicians.
METHODS
It was a cross-sectional observational study conducted in the outpatient departments of tertiary care hospitals in India wherein the 13 Indian Council of Medical Research Rational Use of Medicines Centres are located. Prescriptions not compliant with the standard treatment guidelines and incomplete prescriptions with respect to formulation, dose, duration and frequency were labelled as 'prescriptions having deviations'. A deviation that could result in a drug interaction, lack of response, increased cost, preventable adverse drug reaction (ADR) and/or antimicrobial resistance was labelled as an 'unacceptable deviation'.
RESULTS
Against all the prescriptions assessed, about one tenth of them (475/4838; 9.8%) had unacceptable deviations. However, in 2667/4838 (55.1%) prescriptions, the clinicians had adhered to the treatment guidelines. Two thousand one hundred and seventy-one prescriptions had deviations, of which 475 (21.9%) had unacceptable deviations with pantoprazole (n=54), rabeprazole+domperidone (n=35) and oral enzyme preparations (n=24) as the most frequently prescribed drugs and upper respiratory tract infection (URTI) and hypertension as most common diseases with unacceptable deviations. The potential consequences of deviations were increase in cost (n=301), ADRs (n=254), drug interactions (n=81), lack of therapeutic response (n=77) and antimicrobial resistance (n=72). Major corrective actions proposed for consideration were issuance of an administrative order (n=196) and conducting online training programme (n=108).
INTERPRETATION CONCLUSIONS
The overall prevalence of deviations found was 45 per cent of which unacceptable deviations was estimated to be 9.8 per cent. To minimize the deviations, clinicians recommended online training on rational prescribing and administrative directives as potential interventions.
Topics: Humans; Cross-Sectional Studies; Tertiary Care Centers; Prescriptions; Drug-Related Side Effects and Adverse Reactions; India; Anti-Bacterial Agents; Drug Prescriptions
PubMed: 38528817
DOI: 10.4103/ijmr.ijmr_2309_22 -
British Journal of Cancer Apr 2024
PubMed: 38509357
DOI: 10.1038/s41416-024-02660-4 -
Repurposing of US-FDA-approved drugs as negative modulators of ubiquitin specific protease-7 (USP7).Heliyon Mar 2024Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant...
Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant expression of USP7 facilitates human malignancies by altering the activity of proto-oncogenes/proteins, and tumor suppressor genes. Therefore, USP7 is a validated anti-cancer drug target. In this study, a drug repurposing approach was used to identify new hits against the USP7 enzyme. It is one of the most strategic approaches to find new uses for drugs in a cost- and time-effective way. Nuclear Magnetic Resonance-based screening of 172 drugs identified 11 compounds that bind to the catalytic domain of USP7 with dissociation constant () values in the range of 0.6-1.49 mM. These 11 compounds could thermally destabilize the USP7 enzyme by decreasing its melting temperature up to 9 °C. Molecular docking and simulation studies provided structural insights into the ligand-protein complexes, suggesting that these compounds bind to the putative substrate binding pocket of USP7, and interact with its catalytically important residues. Among the identified 11 hits, compound (oxybutynin), (ketotifen), (pantoprazole sodium), and (escitalopram) also showed anti-cancer activity with an effect on the expression of proto-oncogenes and tumor-suppressor gene at mRNA level in HCT116 cells. The compounds identified in this study can serve as potential leads for further studies.
PubMed: 38468948
DOI: 10.1016/j.heliyon.2024.e26345