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The use of inhibitors of gastric acid secretion (IGAS), especially proton pump inhibitors (PPI), has been associated with increased cardiovascular risk. While the mechanisms involved are not known, there is evidence supporting increased oxidative stress, a major activator of matrix metalloproteinases (MMP), as an important player in such effect. However, there is no study showing whether other IGAS such as histamine H2-receptor blockers (H2RB) cause similar effects. This study aimed at examining whether treatment with the H2RB ranitidine promotes oxidative stress resulting in vascular MMP activation and corresponding functional and structural alterations in the vasculature, as compared with those found with the PPI omeprazole. Male Wistar rats were treated (4 weeks) with vehicle (2% tween 20), omeprazole (10 mg/Kg/day; i.p.) or ranitidine (100 mg/Kg/day; gavage). Then the aorta was collected to perform functional, biochemical, and morphometric analysis. Both ranitidine and omeprazole increased gastric pH and oxidative stress assessed in situ with the fluorescent dye dihydroethidium (DHE) and with lucigenin chemiluminescence assay. Both IGAS augmented vascular activated MMP-2. These findings were associated with aortic remodeling (increased media/lumen ratio and number of cells/μm2). Both IGAS also impaired the endothelium-dependent relaxation induced by acetylcholine (isolated aortic ring preparation). This study provides evidence that the H2RB ranitidine induces vascular dysfunction, redox alterations, and remodeling similar to those found with the PPI omeprazole. These findings strongly suggest that IGAS increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling, which helps to explain the increased cardiovascular risk associated with the use of those drugs. [ABSTRACT FROM AUTHOR]

Nitrosamine compounds pose a significant concern as potential carcinogens, prompting heightened scrutiny from regulatory bodies, particularly regarding their presence in pharmaceuticals. The detection of unacceptable levels of N‐nitrosodiethylamine (NDMA) in ranitidine has led to widespread recalls, driving interest in alternative medications such as nizatidine, which shares a similar pharmacological class and is used to treat various gastrointestinal conditions. Despite fewer reports on NDMA levels in nizatidine, its structural similarity to ranitidine, characterized by a tertiary amine, underscores the potential for NDMA formation. Addressing the analytical challenges associated with nitrosamine detection, this study focuses on developing and validating an ultra‐high pressure liquid chromatography triple quadrupole mass spectrometry (UHPLC–MS/MS) method for quantifying NDMA in both nizatidine active pharmaceutical ingredients and tablet formulations. Method validation adheres to International Council for Harmonisation recommendations, with a demonstrated linear range of 0.25–100 ng/mL for NDMA, exhibiting excellent linearity (regression coefficient >0.999) and efficient recovery rates ranging from 95.98% to 109.57%. The method shows high sensitivity, with limits of detection and quantification of 0.25 and 0.5 ng/mL, respectively. The developed UHPLC–MS/MS method offers a simple, precise, accurate, and selective approach for monitoring NDMA levels in nizatidine formulations available in Australia, promising enhanced sensitivity and specificity with limits of quantification in the ppb and sub‐ppb ranges. [ABSTRACT FROM AUTHOR]

N-nitrosodimethylamine is a carcinogenic agent accidentally found in ranitidine formulations. For the products to be safe for human use and quality control test, the estimation of N-nitrosodimethylamine in ranitidine is significantly important. The goal of this study was to use liquid chromatography with tandem mass spectrometric technique for the development and validation of N-nitrosodimethylamine in ranitidine drug and tablets. The proposed approach was utilized to estimate routine analysis of N-nitrosodimethylamine in ranitidine drug and tablets. The injection volume 20 µl and wavelength 254 nm was selected for N-nitrosodimethylamine and ranitidine quantification. Binary mobile phase in a gradient mode was used for the study. The mixture of solvent A (0.1 % formic acid in water) and solvent B (0.1 % formic acid in methanol) was used as the mobile phase. The flow rate of 0.6 ml/min in gradient mode with complete run time of 14 min was used for the analysis. For N-nitrosodimethylamine analysis multiple reaction monitoring transitions were 75.80/44.20 (quantitative analysis) and 75.80/58.20 (qualitative analysis). N-nitrosodimethylamine retention time was found at 1.25 min. For N-nitrosodimethylamine, the limit of detection was 0.3 ng/ml and limit of quantitation was found to be 1 ng/ml. The linearity range for N-nitrosodimethylamine was decided as 1, 2, 5, 10, 20 and 50 ng/ml from its intensity response. The regression value observed in a linearity graph was 0.9999. The method was specific (no interference of any peak), validated for its accuracy (98.07 to 100.22±1.7565), precision (98.64 to 99.44±0.9083) and robustness (does not effect on developed method by slight change in flow rate and column temperature). In the validation investigation, the quality control levels lower quality control (4 ng/ml), middle quality control (8 ng/ml) and higher quality control (40 ng/ml) were used. Newly developed and validated method for N-nitrosodimethylamine in ranitidine by liquid chromatography with tandem mass spectrometry was accurate, precise and sensitive. The developed method was further used for routine analysis of N-nitrosodimethylamine in ranitidine drug and tablets. [ABSTRACT FROM AUTHOR]

Rationale: N‐Nitroso dimethylamine (NDMA) is a mutagenic impurity detected in several ranitidine products. The amino functional group of ranitidine is a risk factor for classical nitrosation‐induced NDMA formation in ranitidine drug products during storage conditions. The United States Food and Drug Administration (US FDA) recommended the use of antioxidants to control NDMA in drug products. Considering the need for sensitive analytics, a liquid chromatography/high‐resolution mass spectrometry (LC–HRMS) method was developed and validated to detect NDMA in this pilot study to demonstrate the antioxidants as inhibitors of nitrosation reactions. Methods: The method, utilizing an EC‐C18 column and tuned to atmospheric pressure chemical ionization/selected ion monitoring (APCI/SIM) mode, separated NDMA (m/z: 75.0553; tR: 3.71 min) and ranitidine (m/z: 315.1485; tR: 8.61 min). APCI mode exhibited four times higher sensitivity to NDMA than electrospray ionization (ESI) mode. Classical nitrosation of the dimethyl amino group of ranitidine was studied with sodium nitrite in solid pellets. Antioxidants (alpha‐tocopherol, ascorbic acid, and trolox) were evaluated as NDMA attenuators in ranitidine pellets under vulnerable storage conditions. The developed method quantified NDMA levels in samples, extracted with methanol through vortex shaking for 45 min. Results: The method achieved a limit of detection (LOD) and limit of quantitation (LOQ) of 0.01 and 0.05 ng/mL, respectively, with linearity within 1–5000 ng/mL (R1: 0.9995). It demonstrated good intra‐day and inter‐day precision (% RSD [relative standard deviation]: <2) and accuracy (96.83%–101.72%). Nitrosation of ranitidine induced by nitrite was significant (p < 0.001; R2 = 0.9579) at various sodium nitrite levels. All antioxidants efficiently attenuated NDMA formation during ranitidine nitrosation. Ascorbic acid exhibited the highest NDMA attenuation (96.98%), followed by trolox (90.58%). This study recommends 1% ascorbic acid and trolox as potent NDMA attenuators in ranitidine drug products. Conclusions: This study compared the effectiveness of antioxidants as NDMA attenuators in ranitidine under storage conditions susceptible to NDMA generation. The study concluded that ascorbic acid and trolox are potent inhibitors of NDMA formation and nitrosation attenuators in ranitidine drug products. [ABSTRACT FROM AUTHOR]

Introduction: Hypomagnesaemia secondary to the use of proton-pump inhibitor (PPI) is associated with the reduction of blood pressure. Objectives: To determine the effect of PPI and ranitidine on the reduction of serum magnesium level and blood pressure in chronic hemodialysis patients with hypotension. Patients and Methods: In this double-blind randomized clinical trial, 44 hemodialysis patients who met the requirements entered the study. First, blood sample was taken from each of the patients and their serum magnesium level as well as their blood pressure was checked and recorded. Then, the patients in the intervention group received daily doses of ranitidine placebo (150 mg) and pantoprazole (40 mg) and those in the control group received daily doses of pantoprazole placebo (40 mg) and ranitidine (150 mg) for three months. After the intervention, blood samples were taken again in order to assess the patients' serum magnesium level. The obtained data were fed into SPSS Software and analyzed. Results: The mean age of the patients was 60.14±12.98 years. Moreover, 63.6% of the total patients were female. In the group of patients who had received pantoprazole, diastolic pressure reduced significantly at the end of the study as compared to the beginning of the study. Moreover, in the patients receiving pantoprazole indicated a significant reduction of magnesium at the end of the study as compared to the beginning of the study. Conclusion: In this study, a significant relationship was also observed between the use of PPI and hypomagnesemia in hemodialysis patients. Trial registration: The trial protocol was approved in the Iranian Registry of Clinical Trials (identifier: IRCT20150808023559N19; https://en.irct.ir/trial/42478, ethical code# IR.ARUMS. REC.1398.295). [ABSTRACT FROM AUTHOR]

The water contaminated with the typical gastric drug Ranitidine (RAN) was treated via peroxomonosulfate (PMS) alone・ The effects of different oxidants, initial pollutant concentration, PMS concentration, initial pH, humic acid, and co-existing anion concentration on the degradation efficiency of RAN were investigated. The results showed that 0. 5 mmol/L PMS under neutral conditions degraded 93. 49% of RAN (10 mg/L) w让hin 30 min, while other oxidants(i.匕 hydrogen peroxide H2O2, persulfate PS) were not effective in removing RAN. Moreover, the degradation of RAN by PMS was significantly inhibited under strongly alkaline conditions (pH = 11)・ The presence of low concentrations of Cl enhanced the degradation efficiency of RAN, while SO²4, NO3, CO²3: and humic acid(HA) hindered the RAN removal process・ Reactive oxygen species quenching and trapping experiments revealed that singlet oxygen was the main reactive oxygen species responsible for catalyzing RAN degradation. In add让ion, germination and stem length increased in wheat and radish, indicating that the PMS oxidation process reduced the toxicity of RAN. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Generic medications represent 90% of prescriptions in the US market and provide a tremendous financial benefit for patients. Recently, multiple generic drugs have been recalled due to the presence of carcinogens, predominantly N-nitrosodimethylamine (NDMA), including an extensive recall of extended-release (ER) metformin products in 2020. STUDY DESIGN: Primary pharmaceutical quality testing and database analysis. METHODS: We tested marketed metformin immediate-release (IR) and ER tablets from a wide sample of generic manufacturers for the presence of carcinogenic impurities NDMA and N,N-dimethylformamide (DMF). We examined the association of level of impurity with drug price and the impact of the 2020 FDA recalls on unit price and prescription fill rate. RESULTS: Postrecall NDMA levels were significantly lower in metformin ER samples (standardized mean difference=-2.0; P=.01); however, we found continued presence of carcinogens above the FDA threshold in 2 of 30 IR samples (6.67%). Overall, the presence of contaminant levels was not significantly associated with price for either IR (NDMA: R² =0.142; P=.981; DMF: R² =0.382; P=.436) or ER (NDMA: R² =0.124; P=.142; DMF: R² =0.199; P=.073) samples. Despite recalls, metformin ER prescription fills increased by 8.9% while unit price decreased by 19.61% (P<.05). CONCLUSIONS: Recalls of metformin ER medications were effective in lowering NDMA levels below the FDA threshold; however, some samples of generic metformin still contained carcinogens even after FDA-announced recalls. The absence of any correlation with price indicates that potentially safer products are available on the market for the same price as poorer-quality products. [ABSTRACT FROM AUTHOR]

Feeding disorders of infancy are common in paediatric practice. Among rare causes of this disturbance is diabetes insipidus (DI), which is a clinical syndrome characterized by polyuria, polydypsia and dehydration with hypernatraemia. Central diabetes insipidus (CDI, vasopressin deficiency) is more common in children than nephrogenic diabetes insipidus (NDI, an inability to respond adequately to vasopressin). Regardless of the type of DI, the main goal of treatment is to decrease thirst and urine output and achieve proper ion and fluid balance. We present three cases of infants with feeding difficulties. The first two cases concerned patients with semilobar holoprosencephaly (HPE). Their stories show the importance of knowing the most common abnormalities associated with HPE, such as CDI. The third child had similar problems with feeding which resembled a defect of the central nervous system, but was finally diagnosed as NDI. The diagnostic and therapeutic approach is demonstrated in the paper with special regards to safe management of hypernatraemic dehydration. [ABSTRACT FROM AUTHOR]

During study of ranitidine in dosage form, a new stability indicating HPLC method has been developed and validated with different parameters. At a flow rate of 1 ml/min, the chromatographic conditions were optimized using a mobile phase of Acetonitrile: Water (0.1% OPA) (25:75). Particle size capacity of column was 5 μm; and Column (C18) of 4.6 × 250 mm dimension was used as a stationary phase. The detection was carried out at 314 nm. The method was validated according to ICH guidelines for System suitability, Accuracy, linearity, precision (Intraday & Interday), LOD and LOQ and Robustness of the system. The response was found to be linear in concentration range of 50-300 mgm/ml of Ranitidine. The method was linear, simple, precise and accurate and therefore suitable for routine analysis of drugs in tablet form. The forced degradation studies were also done through exposure of analyte solution to four different stress conditions. [ABSTRACT FROM AUTHOR]

During study of Ondansetron and Ranitidine in bulk and dosage form, a forced degradation study has been carried out with development and validation of RP-HPLC method. At a flow rate of 1 ml/min, the chromatographic conditions were optimized using a mobile phase of Acetonitrile: Water (0.1% OPA) (25:75). The detection was carried out at 314 nm. Particle size capacity of column was 5 μm and Column (C18) of 4.6 × 250 mm dimension was used as a stationary phase. Forced degradation or stability studies was carried out by exposing a drug solution into four different stress conditions like Hydrolytic, Acidic, Alkaline, and oxidative. The method was validated according to ICH guidelines for linearity, Accuracy, precision (Interday), LOD and LOQ. The response was found to be linear in concentration range of 50-300 mmg/ml of Ranitidine and 4-20 mgm/ml of Ondansetron. During Interday Precision of Ranitidine and Ondansetron, %RSD found were less than 2%. LOD of Ranitidine & Ondansetron was found to be 2.1518 and 0.1158, respectively. LOQ of Ranitidine and Ondansetron was found to be 6.5207 and 0.3509, respectively. The method was linear, simple, precise and accurate and therefore suitable for routine analysis of drugs in formulation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical efficacy of recombinant human basic fibroblast growth factor (rh-bFGF) combined with ranitidine in the treatment of recurrent oral ulcer and its effects on serum TNF, IL-2 and T-lymphocyte subsets. Methods: This was a retrospective study. Eighty patients with oral ulcers admitted to First Medical Center, Chinese PLA General Hospital from July 2021 to June 2022 were randomly divided into the control group and the experimental group (n=40). Patients in the control group were given topical treatment with rh-bFGF gel, while those in the experimental group were given oral treatment combined with ranitidine based on the control group, and both groups were treated continuously for 14 days. The therapeutic effect, pain relief time, ulcer healing time, as well as the differences in the levels of inflammatory factors and T-lymphocyte subsets were compared and analyzed between the two groups. Results: The overall response rate of the experimental group was 92.5%, while that of the control group was 75%, with a statistically significant difference(P=0.03). After treatment, inflammatory factors indexes in the experimental group were significantly lower than those in the control group, with statistically significant differences (P=0.00). The indexes of T-lymphocyte subsets in the experimental group were significantly higher than those in the control group after treatment, with statistically significant differences (P=0.00). Conclusion: Recombinant human basic fibroblast growth factor combined with ranitidine is effective in the treatment of recurrent oral ulcers, boasting various benefits such as effectively promoting ulcer healing, reducing pain and inflammatory response, and enhancing immune function. [ABSTRACT FROM AUTHOR]

Introduction: This study compares outcomes after LESS cholecystectomy utilizing epidural versus general anesthesia. Methods: Patients undergoing LESS Cholecystectomy were randomized into receiving epidural or general anesthesia by protocol. Patients used a Visual Analog Scale to rate pain from 0 (no pain) to 10 (severe pain). Data presented as median (mean ± standard deviation). Results: 75 patients underwent LESS cholecystectomy with general anesthesia [32 patients (22% men) after five patients withdrew consent] or epidural anesthesia [23 patients (22% men) after 15 patients withdrew consent]. Respectively, they were of age 38 years (41 ± 15.1) and 47 years (48 ± 13.9), BMI 29 (28 ± 4.9) kg/m2 and 28 (28 ± 3.8) kg/m2, and ASA 2 (2 ± 0.5) and 2 (2 ± 0.3) (p > 0.05 for all). LOS for patients receiving general vs. epidural anesthesia was 72 min (122 ± 104.4) vs. 95 min (113 ± 77.5) (p = 0.25). On POD 0, patients receiving general anesthesia rated pain as 4 (4 ± 2.9) vs. 0 (1 ± 2.2) for epidural anesthesia (p = 0.02). On POD 1, they rated pain as 6 (5 ± 2.3) vs. 6 (6 ± 2.9) (p = 0.68). On POD 6, patients rated pain as 3 (3 ± 2.7) vs. 4 (3 ± 2.2) (p = 1.00). For patient satisfaction with incisional scars for those receiving general vs. epidural anesthesia, patients rated their scars to be 10 (8 ± 3.6) vs. 10 (9 ± 1.2) (p = 0.21). Total costs for the hospital using general vs. epidural anesthesia were found $6,909 (7,167 ± 2,083.8) vs. $6,225 (5,848 ± 1530.1) (p = 0.014), respectively. Patients self-assessed satisfaction on a scale of 1 (worst) to 5 (best) as a 5 (5 ± 0). Conclusions: Patients undergoing LESS cholecystectomy with general vs. epidural anesthesia had similar demographics, LOS, and pain scores. Patients that received epidural anesthesia reported less pain and incurred less cost. Utilization of epidural anesthesia in lieu of general anesthesia for LESS cholecystectomy is safe, reduces pain, and offers potential cost savings. [ABSTRACT FROM AUTHOR]

Wastewater effluent from the pharmaceutical, cosmetic, and chemical industries often contains pharmaceutical contaminants, making the reuse of wastewater a controversial practice. Physical and chemical methods have been unsuccessful in removing these pollutants on a large scale. Microalgal technology has been introduced as a promising tool to tackle this issue. This study evaluated the performance of Trichormus variabilis microalgae in removing three contaminants, namely ranitidine, tramadol, and gabapentin. Three concentrations of each compound were introduced into the microalgal culture medium. The effect of these pharmaceutical concentrations on growth, biomass production, photosynthetic pigments, and protein and lipid content was evaluated and compared with control cultures over 14 days. It was found that T. variabilis was able to remove 61–100% of these drugs. Moreover, the addition of 250 mg L–1 of ranitidine to the algae culture medium led to a 33.4% reduction in biomass growth. Adding 20 mg L–1 of tramadol and 200 mg L–1 of gabapentin caused 30% and 19.2% biomass reductions, respectively. The presence of 100 mg L–1 of gabapentin led to a 38% and up to 14% increase in chlorophyll and carotenoid content in comparison with the control, while the presence of the other drugs reduced the content of chlorophyll and carotenoid. On the other hand, the protein content increased by 254% in the culture media compared to the control media in the presence of 50 mg L–1 ranitidine. Regarding lipid concentration, 20 mg L–1 of tramadol had the most important effect by doubling the lipid content in T. variabilis in comparison with the control. In conclusion, these drugs could be removed to a significant extent by T. variabilis, which is promising for larger scale applications. [ABSTRACT FROM AUTHOR]

The present study was designed to assess Tradescantia spathacea's antidiabetic ability, as well as the antiulcer activity of the entire plant extract. The diabetic condition was evaluated using Streptozotocin's oral glucose tolerance test, diabetes-alloxan, and diabetes-models. Antiulcer activities were observed in rats where gastric ulcers were either caused by oral administration of ethanol, or pyloric ligation. Standards include ranitidine, glibenclamide and sucralfate. In all models, the blood glucose levels of animals treated with the test extract were found to be significantly lower compared to diabetic care. Similarly, in all models, the ulcer index in the animals treated with the test extract was found to be significantly lower relative to the animals under vehicle supervision. Our findings say T. Spathacea extract has essential anti-diabetic properties, as well as antiulcer properties. [ABSTRACT FROM AUTHOR]

Since the initial 2018 recall of angiotensin receptor blockers due to unacceptable levels of mutagenic N-nitrosodimethylamine (NDMA) impurity, numerous drug products delivering diverse active pharmaceutical ingredients (APIs) have been recalled. Regulators and the industry are working together to understand and address this widescale problem. Conventional analysis of NDMA utilizes liquid or gas chromatography-based procedures that can involve complicated sample preparation and slow sample analysis. Selected ion flow tube mass spectrometry (SIFT-MS) analyses NDMA directly in the gas phase using soft chemical ionization, with an LOQ of 2 ng g−1. Through the novel application of the multiple headspace extraction (MHE) technique, NDMA was quantified directly and rapidly from the drug product without dissolution, at levels well below the regulatory acceptable intake of 96 ng day−1. A comparative analysis of recalled metformin using MHE-SIFT-MS and a conventional liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS) method showed good agreement. Use of the novel MHE-SIFT-MS approach may enable a wider screening of drug products to be conducted, since it provides around a three-fold increase in daily sample throughput. [ABSTRACT FROM AUTHOR]

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid® 244FP and poloxamer® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect. [ABSTRACT FROM AUTHOR]

The use of acid suppression therapy (AST) is a common approach for managing a wide spectrum of acid peptic disorders. Histamine type 2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are the most widely prescribed AST in routine clinical practice. However, an exponential surge in the prescriptions of PPIs, such as Omeprazole, Esomeprazole, Pantoprazole, Lansoprazole in recent years and their associated adverse effects have raised concern about their inappropriate and overuse, both in children and adults. To address these issues, a three-step modified Delphi polling process was employed to establish best practice consensus statements for rationalizing the use of acid suppressants. A multidisciplinary expert panel of 13 health professionals across medical specialties, including gastroenterologists, hepatologists, pediatric gastroenterologists, pediatricians, otolaryngologists, cardiologists, nephrologists, gynecologist and orthopedists actively contributed to this collaborative process of consensus development. The expert panel proposed 21 consensus statements providing best practice points on the general use and safety of acid suppressants based on a comprehensive review of scientific literature and clinical expertise. The panel also collaboratively developed a PPI deprescribing algorithm. Altogether, this consensus paper offers evidence-based recommendations and guidance for the rational use of acid suppressants with a blueprint for deprescribing PPIs. This consensus paper contributes to aiding primary care practitioners in improving patient outcomes and minimizing healthcare costs. Additionally, it enhances patient safety and curtail inappropriate usage. [ABSTRACT FROM AUTHOR]

This study investigated the use of fully gelatinated durian seed starch as an excipient in Ranitidine HCl Non-Effervescent Buoyancy Tablets (NEFT). The simplex lattice design method was used to formulate the optimum composition of the formula, including fully gelatinated durian seed starch, PVP K30, and magnesium stearate. Physically modified durian seed starch is expected to increase the release time of active substances in the body. The experiment was conducted for six months by measuring the physical properties of the granule, tablet hardness, solubility, and friability. Results showed that the optimum formula (27.74 mg durian seed starch, 1.5 mg PVP K30, 0.76 mg magnesium stearate) produced ranitidine HCl NEFT tablets with optimal properties. This research may contribute to the development of effective tablet formulations. [ABSTRACT FROM AUTHOR]

Introduction: Ranitidine, a histamine H2-receptor antagonist (H2RA), is indicated in the management of gastric acid-related disorders. In 2020, the European Medicines Agency (EMA) recommended suspension of all ranitidine-containing medicines in the European Union (EU) due to the presence of N-nitrosodimethylamine (NDMA) impurities, which were considered to be carcinogenic. The aim of this study was to investigate the impact of regulatory intervention on use patterns of ranitidine-containing medicines and their therapeutic alternatives. Objectives: The aim was to study drug utilisation patterns of ranitidine and report discernible trends in treatment discontinuation and switching to alternative medications. Methods: This retrospective, population-based cohort study was conducted using primary care records from six European countries between 2017 and 2023. To explore drug utilisation patterns, we calculated (1) incident use of ranitidine, other H2RAs, and other alternative drugs for the treatment of gastric ulcer and/or gastric bleeding; (2) ranitidine discontinuation; and (3) switching from ranitidine to alternative drugs (H2RAs, proton-pump inhibitors [PPIs], and other medicinal products for acid-related disorders). Results: During the study period, 385,273 new ranitidine users were observed, with most users being female and aged 18–74 years. Ranitidine was the most commonly prescribed H2RA in the pre-referral period (September 2017–August 2019), with incidence rates between 0.8 and 9.0/1000 person years (PY). A steep decline to 0.3–3.8/1000 PY was observed in the referral period (September 2019–March 2020), eventually dropping to 0.0–0.4/1000 PY in the post-referral period (April 2020–March 2022). Switching from ranitidine to alternative drugs increased in the post-referral period, with the majority of patients switching to PPIs. Discontinuation of ranitidine use ranged from 270 to 380/1000 users in 2017 and decreased over time. Conclusions: Ranitidine was commonly used prior to referral, but it was subsequently discontinued and replaced primarily with PPIs. [ABSTRACT FROM AUTHOR]

Background: For gastrointestinal diseases Osbeckia crinita (O. crinita) has been traditionally used among different parts of Northeast India. The present study aims to evaluate the toxicity and antiulcer activity of O. crinita methanolic leaf extract. Method: For sub-acute toxicity study, repeated oral doses of 150 mg, 300 mg and 600 mg extract of the plant O. crinita per kg body weight of mice were administered for 28 days, and analyzed the hematological and biochemical parameters. The effect of crude methanolic extract of the plant on ethanol-induce peptic ulcer was studied using repeated dosing (200 mg/kg bw) for 6, 10 and 14 days, respectively. Ranitidine (30 mg/kg bw) was used as standard drug. Antiulcer activity was assessed by measuring Ulcer index, healing percentage, gross macroscopic lesions, protein and carbohydrate content along with histopathology and ultra-structural observation. Result: LD50 value was found to be more than 2000 mg/kg body weight. The sub-acute toxicity study showed that at a dose of 600 mg/kg bw of mice significant changes were observed in hematological and biochemical parameters. Six, ten and fourteen day's treatment with the plant extract exhibited significant increase in ulcer protection by 62.09%, 81.04% and 90.06%, respectively. As compared to negative ulcerated mice, O. crinita treated mice showed higher level of protein and carbohydrate content. The histological and scanning electron microscopic observations showed treatment with O. crinita resulted in comparatively better gastric healing in a time dependent manner. Conclusion: Based on the results, it was concluded that O. crinita extract possesses peptic ulcer protective potency comparable to ranitidine, which justifies the use of this plant for ulcer treatment. [ABSTRACT FROM AUTHOR]

The aim of the present research was to develop a magnetic coconut carbon composite (Fe2O3/Fe3O4@CNC) as a solid-phase extraction (SPE) sorbent for the analysis of carcinogenic N-nitrosodimethylamine (NDMA) in pharmaceuticals. Coconut composites modified with Fe2O3 and Fe3O4 were prepared and applied as SPE sorbent for the extraction of NDMA in pharmaceuticals. The sorbent was characterized with X-Ray, infrared spectroscopy and nitrogen porosimetry. The best ions for the Gas Chromatography-Mass Spectrometry with Selected Ion Monitoring (GC-MS/SIM) analysis were m/z 74 and 42 for NDMA, and m/z 80 and 46 for NDMA-d6 internal standard. System has offered great method performance in terms of sensitivity limit of quantitation (LOQ) 16 ng kg−1. The developed sorbent has enhanced the sensitivity and speed of analysis. The developed method was applied to authenticate the presence of NDMA in various pharmaceutical samples. Among the analyzed samples, NDMA impurities were relatively identified at high amounts in nizatidine samples.Highlights NDMA was verified in ranitidine, metformin and nizatidineFe2O3/Fe3O4@CNC composite was used for NDMA identification without pretreatmentSPE sorbent enhance sensitivity, reduce analysis time, sustain accuracy & precisionHigh level of NDMA impurity were found in nizatidine pharmaceuticals.

Permeability has an important effect on drug absorption. In this study, the effect of different concentrations of sodium sulfobutyl ether-β-cyclodextrin (SBE-β-CD) on the absorption of ranitidine was investigated to examine the mechanism of permeability changes. The results of a parallel artificial membrane permeability assay (PAMPA) showed that increasing the concentration of sodium sulfobutyl ether-β-cyclodextrin, 0, 0.12% (w/v), 0.36% (w/v) and 3.6% (w/v), respectively, caused the apparent permeability coefficient of ranitidine to decrease to 4.62 × 10−5, 4.5 × 10−5, 3.61 × 10−5 and 1.08 × 10−5 in Caco-2 cells, respectively. The same results were obtained from an oral pharmacokinetic study in rats. Further studies indicated that SBE-β-CD significantly increased the zeta potential of ranitidine. SBE-β-CD interacted with ranitidine charges to form a complex that reduced ranitidine permeability, and SBE-β-CD should be chosen with caution for drugs with poor permeability. [ABSTRACT FROM AUTHOR]

A method has been designed based on gas chromatography with flame ionization detection (FID) for the separation and analyses of ranitidine, famotidine and metformin after pre-column derivatization with trifluoroacetylacetone and ethyl chloroformate. DB-1 (30 m × 0.32 mm id) column with film thickness 0.25 μm was used for the separation at an initial temperature of column was 100°C for 2 min, and ramping at 20°C/min up to 250°C, with a hold time of 3 min. The rate of nitrogen flow was 2.5 mL/min and FID was used for detection. Complete separation was obtained between all the three drugs including excess of derivatization reagents. Linear calibration curves and detection limits were obtained in the ranges 0.1–30 μg/mL and 0.011–0.015 μg/mL. The procedure was repeatable in terms of peak heights/peak areas and retention time (n  = 5) for derivatization, quantitation and separation with relative standard deviations (RSDs) within 2.0–3.0%. The approach was examined for the analyses of drug products and serum after the intake of the drugs by healthy volunteers, and recoveries were obtained within 95–98% with RSDs 2.4–3.1%. [ABSTRACT FROM AUTHOR]

Overview of various analytical methods for estimating anti-histaminic (H2 Receptor blockers) drugs, particularly for determining their concentration percentage (assay) by analytical methods developed on analytical instruments i.e., UV visible Spectrophotometer, High-Performance Liquid Chromatography, and Hyphenated techniques. The review includes a literature survey of H2 receptor blocker drugs namely cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid, Pepcid AC), and nizatidine (Axid). The examined literature survey addressed chromatographic (HPLC) and UV visible spectrophotometric methods with LC-MS/MS methods used in pure forms, pharmaceutical formulations, human plasma, and other biological fluids for their estimation. In the case of validation parameters, mostly Linearity, Recovery study, LOD, and LOQ were considered and mentioned. This review helps researchers to get detailed information regarding various analytical methods of development and validation for H2 receptor antagonists. [ABSTRACT FROM AUTHOR]

Histamine type-2-receptor antagonist drugs (H2-antagonists) have been used as standard treatment to prevent hypersensitivity reactions (HRs) in paclitaxel-containing regimens, however, their use has been strongly questioned. Ranitidine has been the most widely used H2-antagonist. Therefore, especially after its withdrawal from the market, the objective of this study is to determine the impact of its elimination from premedication on HR incidence. A cohort, multicenter, observational, prospective, and non-inferiority study, including paclitaxel-naïve cancer patients, designed to determine the incidence of HRs of any grade associated with paclitaxel administration and analyze non-inferiority against the incidence estimated in the literature (20%), with 5% as the maximum difference (Δ). Patients with a solid neoplasm of any type/stage, who initiated treatment with paclitaxel without H2-antagonists in the premedication regimen were enrolled. A total of 441 patients were included, of whom 50 presented 54 HRs of any grade. The cumulative incidence was 11.3% (95%CI 8.5–14.7), thus fulfilling the hypothesis of non-inferiority. Of the overall HRs detected, 15 were grade ≥ 3 with a cumulative incidence of 3.4% (95%CI 1.9–5.5). This study demonstrates that the elimination of ranitidine from paclitaxel premedication schedules is non-inferior in the development of HRs of any grade compared to the administration of H2-antagonists. [ABSTRACT FROM AUTHOR]

Computational models based on recent maps of the RBC proteome suggest that mature erythrocytes may harbor targets for common drugs. This prediction is relevant to RBC storage in the blood bank, in which the impact of small molecule drugs or other xenometabolites deriving from dietary, iatrogenic, or environmental exposures ("exposome") may alter erythrocyte energy and redox metabolism and, in so doing, affect red cell storage quality and posttransfusion efficacy. To test this prediction, here we provide a comprehensive characterization of the blood donor exposome, including the detection of common prescription and over-the-counter drugs in blood units donated by 250 healthy volunteers in the Recipient Epidemiology and Donor Evaluation Study III Red Blood Cell-Omics (REDS-III RBC-Omics) Study. Based on high-throughput drug screenings of 1366 FDA-approved drugs, we report that approximately 65% of the tested drugs had an impact on erythrocyte metabolism. Machine learning models built using metabolites as predictors were able to accurately predict drugs for several drug classes/targets (bisphosphonates, anticholinergics, calcium channel blockers, adrenergics, proton pump inhibitors, antimetabolites, selective serotonin reuptake inhibitors, and mTOR), suggesting that these drugs have a direct, conserved, and substantial impact on erythrocyte metabolism. As a proof of principle, here we show that the antacid ranitidine - though rarely detected in the blood donor population - has a strong effect on RBC markers of storage quality in vitro. We thus show that supplementation of blood units stored in bags with ranitidine could - through mechanisms involving sphingosine 1-phosphate-dependent modulation of erythrocyte glycolysis and/or direct binding to hemoglobin - improve erythrocyte metabolism and storage quality.