scholarly journals Evaluation of an Innovative Over-the-Counter Treatment for Symptoms of Reflux Disease: Quick-Dissolving Alginate Granules

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Vicki Strugala ◽  
Peter W. Dettmar ◽  
Edward C. M. Thomas
Keyword(s):  
Single Dose ◽  
Product Development ◽  
Test Meal ◽  
Market Research ◽  
Gastric Retention ◽  
Over The Counter ◽  
Product Formulation ◽  
Taste Evaluation ◽  
Good Flavour

Traditional antacids and alginate-based reflux suppressants are OTC products commonly used to treat reflux symptoms. There has been a lack of innovation of new formulations in this therapy area despite consumers finding established products unpalatable. Here we evaluate a novel product formulation which takes the form of quick-dissolving alginate granules in single-dose sachets (Gaviscon Direct Powder (GDP)). Market research and taste evaluation confirmed that reflux sufferers considered GDP to have good flavour and taste, no chalky aftertaste and dissolved rapidly in the mouth with 68% noting so within 10 seconds. GDP was considered convenient and easy to use. The consumer-driven product development was also shown to form a strong alginate raft in standardised in vitro conditions that met the specifications of the BP monograph (raft strength > 7.5 g). Gastric retention of GDP and a test meal was investigated in healthy volunteers using gamma scintigraphy in comparison to Liquid Gaviscon. Both products formed an alginate raft in the stomach above the test meal and emptied after the meal. The gastric retention of the GDP product was found to be noninferior to Liquid Gaviscon. In conclusion, the innovative GDP product formed an effective raft and was well liked by consumers.

Novel Swellable/Expandable Gastroretentive Floating Films of Gliclazide Folded in Capsule Shell for the Effective Management of Diabetes Mellitus: Formulation Development, Optimization and In vitro Evaluation

2020 ◽  
Vol 15 ◽  
Author(s):  
Diksha Sharma ◽  
Deepak Sharma
Keyword(s):  
Diabetes Mellitus ◽  
Drug Absorption ◽  
Gastric Fluid ◽  
Stability Study ◽  
Gastric Retention ◽  
Effective Management ◽  
In Vitro Evaluation ◽  
Capsule Shell ◽  
Study Results

Background: Gliclazide (GLZ) belongs to the second-generation of sulphonylureas, is a drug of choice for the management of type II DM. It belongs to BCS Class II. The major site of drug absorption for GLZ is the stomach; it displayed variation in the drug absorption rate and bioavailability due to the shorter gastric retention time. Floating mechanism performance gets affected when the gastric fluid level not sufficiently higher, which ultimately obstructs the floating behavior, which is the major limitation of reported formulations. This limitation can get over by folded the film into the capsule shell that dissolved in gastric fluid and film swell/expands to dimensions higher than pylorus sphincter (12mm), thus prevents its evacuation. Objective: To explore the floating mechanism in the designing of films along with a tendency to expand by swelling and unfolding by utilizing a mixture of hydrophilic and hydrophobic polymer to achieve the controlled drug delivery and prolonged gastric retention of drug. Methods: The gastroretentive floating films were formulated by the solvent casting technique using 32 full factorial design and subjected to in vitro evaluation parameters, drug-excipient compatibility, X-ray diffraction and accelerated stability study. Results: The pre-formulation study established the purity and identification of drug. FTIR study confirmed no drug excipient interaction. F3, F6, and F9 were optimized based on in vitro floating characteristics, swelling/expanding ability, and unfolding time study. All developed formulations were unfolded within 14-22 min after capsule disintegration. The F3 was selected as final formulation as its ability to control the release of drug for 24 hrs followed by Zero-order kinetics having super case 2 transport. XRD confirmed the amorphousness of drug within formulation. The stability study results revealed that formulation was quite stable at extreme storage condition. Conclusion: The developed novel formulation has a good potential for the effective management and treatment of Diabetes Mellitus.

scholarly journals Onset of acid-neutralizing action of a calcium/magnesium carbonate-based antacid using an artificial stomach model: an in vitro evaluation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maxim Voropaiev ◽  
Deborah Nock
Keyword(s):  
In Vitro Study ◽  
Magnesium Carbonate ◽  
Human Gastrointestinal Tract ◽  
Pepsin Activity ◽  
Onset Of Action ◽  
Over The Counter ◽  
Calcium Magnesium ◽  
Secondary Objective ◽  
Time Required

Abstract Background Calcium carbonate antacids are potent over-the-counter antacids, made more effective by adding magnesium carbonate (as in Rennie, Bayer). However, published studies on their onset of action are scarce. Therefore, we carried out an in vitro study comparing Rennie and placebo under simulated conditions of the human stomach (artificial stomach model) to reconfirm the onset of action of Rennie. Methods The validated Simulator of the Human Intestinal Microbial Ecosystem apparatus (SHIME, ProDigest, Belgium) was used, comprising five reactors simulating different parts of the human gastrointestinal tract. Both Rennie and placebo were dosed at two tablets per incubation over six independent, 2-h stomach incubations each. Primary objectives: to evaluate the time required to achieve pH 3.0, 3.5, 4.0 and 4.5, as well as the maximum pH reached. Secondary objective: to evaluate pepsin activity over the entire 2-h gastric incubation. Results After addition of Rennie, the gastric medium reached a pH of 3.0 within 40 s. The maximum pH of 5.24 was maintained for almost 10 min. In contrast, the maximum pH with placebo was 1.28 during the entire gastric simulation. Furthermore, Rennie strongly reduced the activity of mucosa-damaging pepsin during the period of increased pH. With placebo, the lower pH resulted in consistently high loads of digested peptides, reflecting the high cumulative and instantaneous pepsin activity. Conclusions New data is a critical component in informed decision making. Our data confirm the high efficacy and fast onset of acid-neutralizing action of Rennie, which begins to work within seconds.

Independent and combined effects of biotin and hemolysis on high-sensitivity cardiac troponin assays

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Kellisha Harley ◽  
Sarah Bissonnette ◽  
Rosanna Inzitari ◽  
Karen Schulz ◽  
Fred S. Apple ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Clinical Laboratory ◽  
Troponin T ◽  
High Sensitivity ◽  
Combined Effects ◽  
Over The Counter ◽  
Heparin Plasma ◽  
Abbott Architect ◽  
Roche Cobas

Abstract Objectives This study compared the independent and combined effects of hemolysis and biotin on cardiac troponin measurements across nine high-sensitivity cardiac troponin (hs-cTn) assays. Methods Parallel cTn measurements were made in pooled lithium heparin plasma spiked with hemolysate and/or biotin using nine hs-cTn assays: Abbott Alinity, Abbott ARCHITECT i2000, Beckman Access 2, Ortho VITROS XT 7600, Siemens Atellica, Siemens Centaur, Siemens Dimension EXL cTnI, and two Roche Cobas e 411 Elecsys Troponin T-hs cTnT assays (outside US versions, with and without increased biotin tolerance). Absolute and percent cTn recovery relative to two baseline concentrations were determined in spiked samples and compared to manufacturer’s claims. Results All assays except the Ortho VITROS XT 7600 showed hemolysis and biotin interference thresholds equivalent to or greater than manufacturer’s claims. While imprecision confounded analysis of Ortho VITROS XT 7600 data, evidence of biotin interference was lacking. Increasing biotin concentration led to decreasing cTn recovery in three assays, specifically both Roche Cobas e 411 Elecsys Troponin T-hs assays and the Siemens Dimension EXL. While one of the Roche assays was the most susceptible to biotin among the nine studied, a new version showed reduced biotin interference by approximately 100-fold compared to its predecessor. Increasing hemolysis also generally led to decreasing cTn recovery for susceptible assays, specifically the Beckman Access 2, Ortho VITROS XT 7600, and both Roche Cobas e 411 Elecsys assays. Equivalent biotin and hemolysis interference thresholds were observed at the two cTn concentrations considered for all but two assays (Beckman Access 2 and Ortho VITROS XT 7600). When biotin and hemolysis were present in combination, biotin interference thresholds decreased with increasing hemolysis for two susceptible assays (Roche Cobas e 411 Elecsys and Siemens Dimension EXL). Conclusions Both Roche Cobas e 411 Elecsys as well as Ortho VITROS XT assays were susceptible to interference from in vitro hemolysis at levels routinely encountered in clinical laboratory samples (0–3 g/L free hemoglobin), leading to falsely low cTn recovery up to 3 ng/L or 13%. While most assays are not susceptible to biotin at levels expected with over-the-counter supplementation, severely reduced cTn recovery is possible at biotin levels of 10–2000 ng/mL (41–8,180 nmol/L) for some assays. Due to potential additive effects, analytical interferences should not be considered in isolation.

scholarly journals Evaluation of a Novel Therapeutic Approach to Treating Severe Pneumococcal Infection Using a Mouse Model

2009 ◽  
Vol 16 (6) ◽  
pp. 806-810 ◽  
Author(s):  
Nikkol Melnick ◽  
Gowrisankar Rajam ◽  
George M. Carlone ◽  
Jacquelyn S. Sampson ◽  
Edwin W. Ades
Keyword(s):  
Single Dose ◽  
Combination Therapy ◽  
Polymorphonuclear Leukocytes ◽  
Low Dose ◽  
Control Level ◽  
Pneumococcal Infection ◽  
Amino Acid Peptide ◽  
Opsonophagocytic Killing

ABSTRACT P4, a 28-amino-acid peptide, is a eukaryotic cellular activator that enhances specific in vitro opsonophagocytic killing of multiple bacterial pathogens. In a previous study, we successfully recreated this phenomenon in mice in vivo by using a two-dose regimen of P4 and pathogen-specific antibodies, which significantly reduced moribundity in mice. For the present study, we hypothesized that the inclusion of a low-dose antibiotic would make it possible to treat the infected mice with a single dose containing a mixture of P4 and a pathogen-specific antibody. A single dose consisting of P4, intravenous immunoglobulin (IVIG), and ceftriaxone effectively reduced moribundity compared to that of untreated controls (n = 10) by 75% (P < 0.05) and rescued all (10 of 10) infected animals (P < 0.05). If rescued animals were reinfected with Streptococcus pneumoniae and treated with a single dose containing P4, IVIG, and ceftriaxone, they could be rerescued. This observation of the repeated successful use of P4 combination therapy demonstrates a low risk of tolerance development. Additionally, we examined the polymorphonuclear leukocytes (PMN) derived from infected mice and observed that P4 enhanced in vitro opsonophagocytic killing (by >80% over the control level; P < 0.05). This finding supports our hypothesis that PMN are activated by P4 during opsonophagocytosis and the recovery of mice from pneumococcal infection. P4 peptide-based combination therapy may offer an alternative and rapid immunotherapy to treat fulminant pneumococcal infection.

In Vitro Chondrotoxicity of Nonsteroidal Anti-inflammatory Drugs and Opioid Medications

2017 ◽  
Vol 45 (14) ◽  
pp. 3345-3350 ◽  
Author(s):  
Geoffrey D. Abrams ◽  
Wenteh Chang ◽  
Jason L. Dragoo
Keyword(s):  
Cell Death ◽  
Single Dose ◽  
Joint Surface ◽  
Saline Control ◽  
Type I ◽  
Dose Equivalent ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Opioid Medications

Background: A variety of medications are administered to the intra-articular space for the relief of joint pain. While amide-type local anesthetics have been extensively studied, there is minimal information regarding the potential chondrotoxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid medications. Purpose: To investigate the in vitro chondrotoxicity of single-dose equivalent concentrations of ketorolac, morphine, meperidine, and fentanyl on human chondrocytes. Study Design: Controlled laboratory study. Methods: Human cartilage was arthroscopically harvested from the intercondylar notch and expanded in vitro. Gene expression of cultured chondrocytes before treatment was performed with quantitative polymerase chain reaction for type I collagen, type II collagen, aggrecan, and SOX9. Chondrocytes were then exposed to 0.01%, 0.02%, and 0.04% morphine sulfate; 0.3% and 0.6% ketorolac tromethamine; 0.5%, 1.0%, and 1.5% meperidine hydrochloride; 0.0005% and 0.001% fentanyl citrate; and saline. A custom bioreactor was used to constantly deliver medications, with the dosage of each medication and the duration of exposure based on standard dose equivalents, medication half-lives, and differences in the surface area between the 6-well plates and the native joint surface. After treatment, a live/dead assay was used to assess chondrocyte viability and if minimal cell death was detected. A subset of samples after treatment was maintained to analyze for possible delayed cell death. Results: All tested concentrations of ketorolac and meperidine caused significantly increased cell death versus the saline control, demonstrating a dose-response relationship. The morphine and fentanyl groups did not show increased chondrotoxicity compared with the saline group, even after 2 weeks of additional culture. Conclusion: In vitro exposure of chondrocytes to single-dose equivalent concentrations of either ketorolac or meperidine demonstrated significant chondrotoxicity, while exposure to morphine or fentanyl did not lead to increased cell death.

scholarly journals Biological Safety Evaluation of 99mTc-DTPA-Ketoconazole for Diagnosis of Fungal Infection

2017 ◽  
Vol 2 (1) ◽  
pp. 1
Author(s):  
Maula Eka Sriyani ◽  
Hendris Wongso ◽  
Eva Maria Widyasari ◽  
Rizky Juwita Sugiharti ◽  
Iim Halimah ◽  
...  
Keyword(s):  
Single Dose ◽  
Fungal Infection ◽  
Radiochemical Purity ◽  
Safety Evaluation ◽  
Fungal Growth ◽  
In Vitro Assays ◽  
Toxic Response ◽  
Biological Safety ◽  
Safety Parameters

Infectious diseases have become one of the leading cause of mortality around the world, including in the Southeast Asia. One of the microbial that cause infection is fungi. Occasionally, deep-seated fungal infection is difficult to detect using conventional diagnosis methods and therefore leads to inaccurate detection. Our previous research was conducted in order to obtain the labeled compound of <sup>99m</sup>Tc-DTPA-Ketoconazole with a high radiochemical purity (98.40 ± 0.86%). Moreover, the in-vitro assays showed that <sup>99m</sup>Tc-DTPA-Ketoconazole can potentially bind to Candida albicans. On the other hand, in clinical routine use, diagnostic kit should be safe for the patients. Consequently, this research was conducted to determine the biological safety parameters of <sup>99m</sup>Tc-DTPA-Ketoconazole on the animal study, including single dose and acute toxicity test, sterility, and apirogenicity test. The results showed that both the single dose at 34.6 μCi and dose until 149 times of the single dose did not stimulate the toxic response to the animals. In addition, the sterility data revealed that there was no microbial growth after 7 days of incubation at 37°C as well as fungal growth after 14 days of incubation at 25°C. Furthermore, the apirogenicity test using rabbits revealed that there was no increase in temperature more than 0.6°C for each animal and not more than 1.5°C of total increase of temperature for all the animals. It is concluded that the <sup>99m</sup>Tc-DTPA-Ketoconazole is satisfy the requirements of biological safety of a radiopharmaceutical and therefore was acceptable for fungal detection in nuclear medicine.

scholarly journals Intravenous injection of cyclophilin A realizes the transient and reversible opening of barrier of neural vasculature through basigin in endothelial cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Narumi Nakada-Honda ◽  
Dan Cui ◽  
Satoshi Matsuda ◽  
Eiji Ikeda
Keyword(s):  
Endothelial Cells ◽  
Single Dose ◽  
Blood Brain Barrier ◽  
Intravenous Injection ◽  
Cyclophilin A ◽  
Brain Barrier ◽  
Blood Brain ◽  
Neural Tissues ◽  
Neural Diseases

AbstractNeural vasculature forms the blood–brain barrier against the delivery of systemically administered therapeutic drugs into parenchyma of neural tissues. Therefore, procedures to open the blood–brain barrier with minimal damage to tissues would lead to the great progress in therapeutic strategy for intractable neural diseases. In this study, through analyses with mouse in vitro brain microvascular endothelial cells and in vivo neural vasculature, we demonstrate that the administration of cyclophilin A (CypA), a ligand of basigin which is expressed in barrier-forming endothelial cells, realizes the artificial opening of blood–brain barrier. Monolayers of endothelial cells lost their barrier properties through the disappearance of claudin-5, an integral tight junction molecule, from cell membranes in a transient and reversible manner. Furthermore, the intravenous injection of a single dose of CypA into mice resulted in the opening of blood–brain barrier for a certain period which enabled the enhanced delivery of systemically administered doxorubicin into the parenchyma of neural tissues. These findings that the pre-injection of a single dose of CypA realizes an artificial, transient as well as reversible opening of blood–brain barrier are considered to be a great step toward the establishment of therapeutic protocols to overcome the intractability of neural diseases.

scholarly journals Vitamin C inhibits SARS coronavirus-2 main protease essential for viral replication

2021 ◽  
Author(s):  
Tek Narsingh Malla ◽  
Suraj Pandey ◽  
Ishwor Poudyal ◽  
Luis Aldama ◽  
Dennis Feliz ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Vitamin C ◽  
Antiviral Treatment ◽  
Cysteine Proteases ◽  
Vitamin Supplement ◽  
Sars Coronavirus ◽  
Over The Counter ◽  
Main Protease ◽  
Approved Drugs

There is an urgent need for anti-viral agents that treat and/or prevent Covid-19 caused by SARS-Coronavirus (CoV-2) infections. The replication of the SARS CoV-2 is dependent on the activity of two cysteine proteases, a papain-like protease, PL-pro, and the 3C-like protease known as main protease Mpro or 3CLpro. The shortest and the safest path to clinical use is the repurposing of drugs with binding affinity to PLpro or 3CLpro that have an established safety profile in humans. Several studies have reported crystal structures of SARS-CoV-2 main protease in complex with FDA approved drugs such as those used in treatment of hepatitis C. Here, we report the crystal structure of 3CLpro in complex Vitamin C (L-ascorbate) bound to the protein's active site at 2.5 Angstrom resolution. We also demonstrate that L-ascorbate inhibits the 3CLpro in vitro at mmol/L concentrations. The crystal structure of the Vitamin C 3CLpro complex may aid future studies on the effect of Vitamin C not only on the coronavirus main protease but on related proteases of other infectious viruses. Since ascorbate is readily available, as an over-the-counter vitamin supplement, our results have the potential for development of a global and inexpensive antiviral treatment.

scholarly journals Design, formulation and characterization of oral disintegrating tablets for lamotrigine

2020 ◽  
Vol 9 (2) ◽  
pp. 60-66
Author(s):  
Raghavendra Kumar Gunda
Keyword(s):  
Pharmaceutical Product ◽  
Fickian Diffusion ◽  
In Vitro Dissolution ◽  
Compression Technique ◽  
Antiepileptic Agent ◽  
Acceptance Criterion ◽  
Sodium Starch Glycolate ◽  
Product Formulation ◽  
Significant Difference

Objective: The purpose of present investigation to formulate, characterize the oral dissolving tablets (ODT) for Lamotrigine. Lamotrigine, an antiepileptic agent, belongs to type –II as per Biopharmaceutical Classification System (BCS). Methods: ODT formulations of Lamotrigine were prepared using different quantities of Sodium Starch Glycolate & Crospovidone employed as Super disintegrants by Direct Compression technique. Nine trials were formulated and evaluated for Pharmaceutical Product Performance. Results: Results shows that all the formulations were lie within the acceptance criterion and the In-vitro dissolution profiles were subjected to kinetic modeling. Conclusion: Formulation (F4) containing 35 mg of Sodium Starch Glycolate & 40 mg of Crospovidone was found to be best one among all and also similar to the Marketed product (LAMICTAL-25) (f2=73.17, f1=3.65 & No significant difference, t=0.0218) to marketed product. Formulation (F4) follows First order, Higuchi’s kinetics, mechanism of drug release was found to be Non-Fickian Diffusion (n= 0.554).

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