Gastric Side Effects Research Articles

Meloxicam-amino acids salts/ion pair complexes with advanced solubility, dissolution, and gastric safety

Amino acids have attracted attention as a potential functional excipient for optimizing biopharmaceutics characteristics of poorly soluble drugs. The amino acids are a diverse class with many functional groups, natural compounds, biocompatible and low molecular weight substances. Two amino acids serine and arginine were investigated with meloxicam. Meloxicam has extremely low solubility; being NSAIDs, gastric upset and ulcer are common side effects. Solid dispersions were produced by precipitation and physical mixing techniques. The produced combinations underwent in vitro dissolution, docking, DSC, FTIR, XRD, solubility and gastric ulcer formation studies. Docking indicated formation of ion pair/salt between the basic amino acid arginine and meloxicam. Both solubility and dissolution rates were increased by up to 3000- and 12-fold, respectively. DSC, FTIR an XRD supported these findings. Rats treated with meloxicam showed loss of surface gastric epithelium integrity and ulceration. The animal group received meloxicam: arginine showed intact gastric mucosa with the surface epithelium and gastric glands well organized and nearly similar to the untreated control. Arginine with the guanidine group that was capable of preserving gastric mucosa after repeated administration for 10 days. This study highlighted the role of arginine as a functional excipient that did not only improve solubility and dissolution rates but ameliorated the long-standing gastric side effects attributed to meloxicam.

Cucurbit[7]uril-based host–guest complexes for improving bioavailability and reducing side effects of piroxicam

Piroxicam (PX) is a nonsteroidal anti-inflammatory drug (NSAID) commonly associated with gastrointestinal (GI) injuries, including dyspepsia, heartburn, inflammation, bleeding, ulceration, and life-threatening perforation. The β-cyclodextrin (β-CD)-based PX formulation (PX@CD) has been shown to reduce gastric side effects by improving PX’s solubility and dissolution rates. However, the solubility of PX can only be increased to a limited extent by β-CD, due to the low binding constant between PX and β-CD (∼100 M−1). As a result, adverse reactions such as epigastric pain and pyrosis are still commonly reported. Cucurbit[7]uril (CB[7]) is a synthetic macrocyclic host compound that binds strongly to various drugs. In this study, we demonstrated that CB[7] forms complexes with PX in the gastric acid environment with a binding constant approximately 70 times higher than that between β-CD and PX. The PX@CB[7] inclusion complexes exhibited rapid dissolution rates in the gastric environment. In addition, PX@CB[7] showed significantly higher oral bioavailability and maximum concentration (Cmax) compared to PX and PX@CD (1:2.5), resulting in improved anti-inflammatory effects in both mouse and rat models. Moreover, PX@CB[7] (1:2.5) had the least adhesion to the gastric mucosa and caused the mildest gastric side effects in rat models when compared to PX, PX@CD (1:2.5), and PX@CB[7] (1:1). Lastly, CB[7] demonstrated good oral biocompatibility in a subacute toxicity evaluation study. These findings indicate that CB[7] could be used as an excipient to improve treatment effectiveness and decrease adverse reactions in orally administered formulations with a favorable safety profile.

Glucagonlike Peptide-1 Receptor Agonists: The Good, the Bad, and the Ugly-Benefits for Glucose Control and Weight Loss with Side Effects of Delaying Gastric Emptying.

Glucagonlike peptide-1 (GLP-1) receptor agonists (RAs) are being increasingly used for glycemic control in patients with diabetes and for weight loss and weight management in obese subjects. There has been recent public awareness of the potential of GLP-1 RAs to delay gastric emptying and cause gastroparesis. By delaying gastric emptying, these agents can complicate the clinical evaluation of patients on these drugs by affecting diagnostic testing for gastroparesis. This article discusses GLP-1 RAs and their effects on gastric emptying, gastric food retention, and gastroparesis. This article highlights how physicians should be attuned to the gastric side effects of these popular therapeutic agents for blood glucose control in people with diabetes and for weight loss and weight management in obese patients.

Fabrication and Evaluation of Aceclofenac-loaded Sustained-Release Mucoadhesive Tablet Composed of Cassia fistula Seed Gum-Grafted-Poly (Sodium Acrylate)

Aim: This study was aimed to fabricate gastroretentive mucoadhesive sustained-release tablets of aceclofenac with Cassia fistula seed gum-grafted-poly(sodium acrylate) and evaluate them.
 Background: Aceclofenac has several gastric related side effects such as increase in acid secretion, gastritis, burning sensation, nausea, vomiting, etc. Sustained-release tablet may reduce these because of slow drug release. But long term use of conventional sustained-release tablets of NSAIDs showed to develop colorectal ulcer. Gastroretentive sustained-release devices may eliminate this problem.
 Objective: The objective was to synthesis Cassia fistula seed gum-grafted-poly(sodium acrylate) and apply it in the fabrication of novel mucoadhesive sustained-release tablet for aceclofenac delivery in stomach.
 Method: CFSG-grafted-poly(sodium acrylate) (CFSG-g-PSA) was synthesized by microwave-assisted free-radical initiation method using ceric ammonium nitrate (CAN) as free-radical initiator. The tablets were prepared with the graft-copolymer by wet granulation technique. Compatibility between drug and graft-copolymer was checked by FTIR, DSC and PXRD. Surface topography of the uncoated matrix tablets was studied by SEM. The tablets were evaluated for weight variation, content uniformity, dimension, disintegration test, mucoadhesive and drug-release. accelerated stability study was also done.
 Results: FTIR, DSC and PXRD studies substantiated the drug-polymer compatibility. The evaluation parameters were within prescribed limit. The study revealed excellent mucoadhesive property over 10 h and sustained-drug-release pattern following zero order kinetic. Similarity factor was found to be 83.4.
 Conclusion: The study demonstrates a simple approach of functionalization of biopolymer towards development of gastroretentive mucoadhesive sustained-release tablet formulation.

Approach to dysmenorrhoea in primary care.

Approach to dysmenorrhoea in primary care.

Role of ADMA/DDAH-1 and iNOS/eNOS signaling in the gastroprotective effect of tadalafil against indomethacin-induced gastric injury.

Non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcers represent a significant clinical concern and adversely affect the quality of life. Inducible nitric oxide synthase/endothelial nitric oxide synthase (iNOS/eNOS) and asymmetric dimethylarginine/ dimethylarginine dimethylaminohydrolase-1 (ADMA/DDAH-1) signaling are key players in gastric ulcer pathogenesis. This work was planned to explore the role of iNOS/eNOS and ADMA/DDAH-1 signaling in rats with indomethacin-induced gastric ulcer, as potential pathways for the gastro-protective effect of tadalafil. Split into 5 separate groups, rats were assigned to control, tadalafil (10mg/kg, p.o), indomethacin (single oral dose of 60mg/kg), indomethacin + pantoprazole (40mg/kg, p.o), and indomethacin + tadalafil (10mg/kg, p.o). The results indicated that pretreatment with tadalafil significantly reduced ulcer index (UI), increased preventive index (PI), and counteracted indomethacin-induced histopathological aberrations. Tadalafil significantly reduced the gastric content of NO while it significantly elevated that of GSH and enhanced SOD activity. It significantly reduced the gastric expression of TNF-α and ADMA while it significantly elevated that of COX-2, PGE-2, and DDAH-1. Western blot analysis revealed that pretreatment with tadalafil significantly reduced iNOS protein expression while it significantly elevated that of eNOS. Collectively, these data suggest that tadalafil exerts potential protective effect against indomethacin-induced ulcer through suppression of inflammation, attenuation of oxidative stress, and boosting of antioxidants. Moreover, tadalafil protective effects are mediated via upregulation of PGE-2 with modulating the signaling pathways of ADMA/DDAH-1, and iNOS/eNOS. As a result, the current evidence corroborates the use of tadalafil in controlling gastric ulcers and preventing NSAID gastric side effects.

Diclofenac Potassium Alone Versus Diclofenac Potassium with Hyoscine-N-butyl Bromide (HBB) in Reduction of Pain in Women Undergoing Office Hysteroscopy: A Double Blind Randomized, Placebo-Controlled Trial.

To compare between oral diclofenac potassium alone versus a combination of it with hyoscine-N-butyl bromide (HBB) in reduction of pain in women undergoing office hysteroscopy. Randomized, double-blind controlled trial. Kasralainy hospital (atertiary hospital). Sixty-Four patients undergoing office hysteroscopy were randomly divided into 2 groups (study group and placebo group) in the ratio of 1:1. Group 1 (study group = 32 participants) received two oral HBB tablets and one tablet of diclofenac potassium and group 2 (placebo group = 32 participants) received two oral placebo tablet similar in size, structure and color to buscopan in addition to the diclofenac tablet. The patient was given the drugs 30-60min before the procedure. There was statistically significant difference between the two groups in the pain score immediately during entry (p value = 0.001) and after 30min of the procedure (p value = < 0.001). And there was a statistically significant difference as regards the side effects (gastric irritation) of the medications (p value = 0.04) between the women participating in the two groups. The combination of diclofenac potassium and HBB helps a lot in decreasing the pain and discomfort during and after performing office hysteroscopy but with more gastric side effects.

Co-Administration of Iron and Bioavailable Curcumin Reduces Levels of Systemic Markers of Inflammation and Oxidative Stress in a Placebo-Controlled Randomised Study.

Ferrous sulphate (FS) is widely used as an iron supplement to treat iron deficiency (ID), but is known to induce inflammation causing gastric side-effects resulting in poor adherence to supplement regimens. Curcumin, a potent antioxidant, has been reported to suppress inflammation via down regulation of NF-κB. The aim of the present double blind, placebo-controlled randomised trial was to assess whether co-administration of FS with a formulated, bioavailable form of curcumin (HydroCurc™) could reduce systemic inflammation and/or gastrointestinal side-effects. This study recruited 155 healthy participants (79 males; 26.42 years ± 0.55 and 76 females; 25.82 years ± 0.54), randomly allocated to one of five different treatment groups: iron and curcumin placebo (FS0_Plac), low dose (18 mg) iron and curcumin placebo (FS18_Plac), low dose iron and curcumin (FS18_Curc), high dose (65 mg) iron and curcumin placebo (FS65_Plac), and high dose iron and curcumin (FS65_Curc). Completed questionnaires and blood samples were collected from all participants at baseline (day 1), mid-point (day 21), and at end-point (day 42). Results showed a significant reduction in IL-6 in the FS65_Curc group (0.06 pg/mL ± 0.02, p = 0.0073) between the mid-point and end-point. There was also a significant reduction in mean plasma TNF levels in the FS65_Curc (0.65 pg/mL ± 0.17, p = 0.0018), FS65_Plac (0.39 pg/mL ± 0.15, p = 0.0363), and FS18_Curc (0.35 pg/mL ± 0.13, p = 0.0288) groups from mid-point to end-point. A significant increase was observed in mean plasma TBARS levels (0.10 µM ± 0.04, p = 0.0283) in the F18_Plac group from baseline to end-point. There was a significant association with darker stools between FS0_Plac vs. FS65_Plac (p = 0.002, Fisher’s exact test) suggesting that high iron dose in the absence of curcumin leads to darker stools. A reduction in inflammation-related markers in response to co-administering supplemental iron alongside formulated curcumin suggests a reduction in systemic inflammation. This supplementation approach may therefore be a more cost effective and convenient alternative to current oral iron-related treatments, with further research to be conducted.

Gastric side effects and the stomach dosimetric analysis in left-sided breast cancer radiotherapy in free-breathing and deep inspiration breath-hold technique

BackgroundAdjuvant radiotherapy following surgery reduces the local recurrence and improves the prognosis. However, a considerable part of patients developed digestive reaction in daily treatment. In order to explore the correlation between breast radiotherapy and gastric toxicity, we investigated the clinic symptoms and stomach dose during DIBH or FB mode while left-sided breast cancer patients (LSBCP) receiving radiotherapy.MethodsIn the study, 124 LSBCP received adjuvant radiotherapy after surgery at our department were analyzed clinical characteristics and enquired about gastrointestinal side effects after treatment. Moreover, dosimetric parameters were assessed.ResultsThere was no statistically significant difference between the two groups in age, T staging, N staging, hormone receptors, human epidermal receptor-2 (HER2), surgical methods, fractionated regimen, and chemotherapy conditions. However, larger stomach volumes and higher fractionated dose (Dmax/F) were associated with a statistically significantly greater risk for acute radiotherapy toxicity. In addition, the use of the DIBH gating technique (FB/DIBH) reduced the incidence of digestive reactions.ConclusionIn order to cut down gastric side effects after breast radiotherapy, large meals should be avoided before treatment. DIBH treatment should be implemented in centers where conditions are satisfied to reduce radiotherapy side effects. Furthermore, dose limitation in stomach should be considered when the radiotherapy plan was formulated, especially for the patients treated with hypofractionated radiotherapy.

The effects of ellagic acid and other pomegranate (Punica granatum L.) derivatives on human gastric cancer AGS cells.

Although surgery with or without (neo)adjuvant chemo/radiotherapy, as the standard treatments, can be suitable therapeutic strategies for gastric cancer, side effects and drug resistance are two main treatment obstacles. It has been discovered that pomegranate and its natural derivatives, especially ellagic acid (EA), offer significant anti-cancer effects while causing trivial side effects. In this study, we aimed to explore the anti-cancer effects of EA on a human gastric adenocarcinoma cell line (AGS) as well as in immunocompromised mice bearing human gastric tumors, for the first time. HPLC was used for determining EA in samples. MTT assay, apoptosis and scratch assay, gelatin zymography, and quantitative RT-PCR were used to determine the anti-cancer properties of different concentrations of pomegranate fruit juice, pomegranate peel extract, and EA. Furthermore, the effects of these compounds were investigated on immunosuppressed C57BL/6 mice carrying human gastric cancer tumors. EA could inhibit the proliferation and migration of gastric cancer cells. It also had significant effects on reducing both expression and activity of MMP-2 and MMP-9. Further, it was demonstrated that with alterations in the expression of genes involved in apoptosis and inflammation including P53, BAX, APAF1, BCL2, iNOS, NF-κB, IL-8, and TNF-α, EA treatment led to increased cancer cell death and reduced inflammation. Furthermore, its use in mice bearing gastric tumors resulted in a significant reduction in tumor volume without any obvious side effects. Ellagic acid exhibited anti-cancer effects on gastric adenocarcinoma, and can be considered as a safe anti-cancer agent for further preclinical studies on this cancer.

Development and Characterization of Eudragit-RL-100-Based Aceclofenac Sustained-Release Matrix Pellets Prepared via Extrusion/Spheronization.

Aceclofenac (AC) is a nonsteroidal anti-inflammatory drug used in the treatment of chronic pain in conditions such as rheumatoid arthritis, with frequent administration during the day. The formulation of sustained release matrix pellets can provide a promising alternative dosage form that controls the release of the drug, with less blood fluctuation and side effects—especially those related to the gastric system. The extrusion/spheronization technique was used to formulate AC matrix pellets. The response surface methodology (version 17.2.02.; Statgraphics Centurion) was used to study the impacts of Eudragit RL 100 and PVP K90 binder solution concentrations on the pellets’ wet mass peak torque, pellet size, and the release of the drug. Statistically, a significant synergistic effect of PVP K90 concentration on the peak torque and pellet size was observed (p = 0.0156 and 0.031, respectively), while Eudragit RL 100 showed significant antagonistic effects (p = 0.042 and 0.013, respectively). The peak torque decreased from 0.513 ± 0.022 to 0.41 ± 0.021 when increasing the Eudragit RL 100 from 0 to 20%, and the pellet size decreased from 0.914 ± 0.047 to 0.789 ± 0.074 nm. The tested independent factors did not significantly affect the drug release in the acidic medium within 2 h, but these pellet formulae maintained the drug release at less than 10% in the acidic medium (pH 1.2), which may decrease gastric irritation side effects. In contrast, a highly significant synergistic effect of Eudragit and highly antagonistic effect of the PVP solution on drug release in the alkaline-pH medium were observed (p = 0.002 and 0.007, respectively). The optimized pellet formula derived from the statistical program, composed of 3.21% Eudragit and 5% PVP solution, showed peak torque of 0.861 ± 0.056 Nm and pellet size of 1090 ± 85 µm, and resulted in a significant retardation effect on the release after 8 h compared to the untreated drug.

Effect of esomeprazole on lipid profile in patients with peptic ulcer

Esomeprazole; a newly introduced PPI has been widely prescribed by healthcare providers due to its improved pharmacokinetic profile. Most users could have other diseases and the PPIs are indicated as acid-suppressor to minimize gastric side effects of polypharmacy. A high percentage of users could suffer from cardiovascular diseases and lipid dysmetabolism. Hence, this study was designed to determine the impact of long-term use of esomeprazole on lipid profile in a normal subject other than having peptic ulcer for which esomeprazole has been indicated. Results confirmed that esomeprazole reduced triglyceride and HDL levels and elevated total cholesterol level and correspondingly LDL level was elevated, however, no effect was noticed with VLDL. To sum up, esomeprazole impaired lipid metabolism in apparently normal healthy individuals apart from having peptic ulcer for which the esomeprazole was indicated, this finding rise a caution during prescribing esomeprazole for the patient with multiple diseases and polypharmacy including cardiovascular ailments.

Formulation and Evaluation of Ketoprofen Emulgels by Model Independent Approach

In the current study, ketoprofen emulgels were prepared using Sodium CMC, Sodium alginate and Hibiscus as gelling agents in order to overcome gastric side effects and to achieve pharmacological response. Pre formulation parameters were performed to know the compatibility of pure drug ketoprofen with polymers CMC, Na alginate, hibiscus prior to the preparation of Emulgel. It indicates that no change was observed in the peak values of the drug in the physical mixture thus providing that both the drug and polymer were said to be compatible with each other. Emulgel of ketoprofen 2.5% w/w was prepared in 3 steps i.e., Preparation of gel, emulsion phases separately and incorporate both phases in homogenizer for a period of 45 min and stabilized it for 2 hrs. The prepared emulgels were evaluated for physical characteristics, drug content, pH, spreadability and in-vitro permeation studies. The physical appearance of all the formulations was creamy white, consistent, homogenous and stable. The pH of the prepared emulgels was found well within the range of 6-7. Release rate kinetics of the drug was studied with in vitro drug permeation data for all the formulations F1 to F9 and results were stated the best fit model for selected formulation F6 were found to be Zero order model with non-fickian diffusion. The formulations were compared with the reference product. The in-vitro dissolution of F6 was nearest to the reference product F10 (f2 = 85.17).

Acute Administration of Bioavailable Curcumin Alongside Ferrous Sulphate Supplements Does Not Impair Iron Absorption in Healthy Adults in a Randomised Trial.

Ferrous sulphate (FS) is a cost effective, readily available iron supplement for iron deficiency (ID). The pro-oxidant effect of oral ferrous iron is known to induce inflammation, causing gastric side-effects and resulting in poor compliance. Curcumin is a potent antioxidant and has also been shown to exhibit iron chelation in-vitro, although it is not established whether these effects are retained in-vivo. The aim of this study was therefore to assess the influence of a formulated bioavailable form of curcumin (HydroCurcTM; 500 mg) on acute iron absorption and status in a double blind, placebo-controlled randomized trial recruiting 155 healthy participants (79 males; 26.42 years ± 0.55 and 76 females; 25.82 years ± 0.54). Participants were randomly allocated to five different treatment groups: iron and curcumin placebo (FS0_Plac), low dose (18 mg) iron and curcumin placebo (FS18_Plac), low dose iron and curcumin (FS18_Curc), high dose (65 mg) iron and curcumin placebo (FS65_Plac), and high dose iron and curcumin (FS65_Curc). Participants were provided with the supplements according to their relevant treatment groups at baseline (0 min), and blood collection was carried out at 0 min and at 180 min following supplementation. In the treatment groups, significant difference was observed in mean serum iron between baseline (0 min) and at end-point (180 min) (F (1, 144) = 331.9, p < 0.0001) with statistically significant intra-group increases after 180 min (p < 0.0001) in the FS18_Plac (8.79 µmol/L), FS18_Curc (11.41 µmol/L), FS65_Plac (19.09 µmol/L), and FS65_Curc (16.39 µmol/L) groups. A significant difference was also observed between the two time points in serum TIBC levels and in whole blood haemoglobin (HGB) in the treatment groups, with a significant increase (1.55%/2.04 g/L) in HGB levels from baseline to end-point observed in the FS65_Curc group (p < 0.05). All groups receiving iron demonstrated an increase in transferrin saturation (TS%) in a dose-related manner, demonstrating that increases in serum iron are translated into increases in physiological iron transportation. This study demonstrates, for the first time, that regardless of ferrous dose, formulated curcumin in the form of HydroCurc™ does not negatively influence acute iron absorption in healthy humans.

Overview on the Discovery and Development of Anti-Inflammatory Drugs: Should the Focus Be on Synthesis or Degradation of PGE2?

Inflammation is a protective response that develops against tissue injury and infection. Chronic inflammation, on the other hand, is the key player in the pathogenesis of many inflammatory disorders including cancer. The cytokine storm, an inflammatory response flaring out of control, is mostly responsible for the mortality in COVID-19 patients. Anti-inflammatory drugs inhibit cyclooxygenases (COX), which are involved in the biosynthesis of prostaglandins that promote inflammation. The conventional non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastric and renal side-effects, as they inhibit both the constitutive COX-1 and the inducible COX-2. The majority of selective COX-2 inhibitors (COXIBs) are without gastric side-effects but are associated with cardiac side-effects on long-term use. The search for anti-inflammatory drugs without side-effects, therefore, has become a dream and ongoing effort of the Pharma companies. As PGE2 is the key mediator of inflammatory disorders, coming up with a strategy to reduce the levels of PGE2 alone without affecting other metabolites may form a better choice for the development of next generation anti-inflammatory drugs. In this direction the options being explored are on synthesis of PGE2-mPGES-1; PGE2 degradation through a specific PG dehydrogenase, 15-PGDH, and by blocking its activity mediated through a specific PGE receptor, EP4. As leukotrienes formed via the 5-lipoxygenase (5-LOX) pathway also play an important role in the mediation of inflammation, efforts are also being made to target both COX and LOX pathways. This review focuses on addressing the following three points: 1) How NSAIDs and COXIBs are associated with gastric, renal and cardiac side-effects; 2) Should the focus be on the targets upstream or downstream of PGE2; and 3) the status of alternative targets being explored for the discovery and development of anti-inflammatory drugs without side-effects.

Benefit of Iron Supplementation with Ferric Sodium EDTA (NaFe &amp;lt;sup&amp;gt;3+&amp;lt;/sup&amp;gt;-EDTA) in the Treatment of Anemia during Pregnancy in Democratic Republic of Congo (FERARI Study)

Background: Oral iron supplements, usually in the form of ferrous salts, are associated with gastric side effects, poor compliance and failure of anemia treatment. To make iron more bioavailable, reduce the gastric side effects and increase the patient compliance, newer iron form, Ferric Sodium EDTA, has become available on the market. Objective: To assess the change in hemoglobin level after iron supplementation with Ferric Sodium EDTA during pregnancy. Materials and Methods: This is a longitudinal study concerning 337 women attending antenatal care in maternity hospitals in the Democratic Republic of Congo from May to December 2020. The study included sociodemographic and anthropometric variables along with type of feed, hemoglobin level at recruitment and after three weeks of taking iron supplement with Ferric Sodium EDTA (Hemoforce Plus Zinc® syrup). For statistical analysis, we used t-test or ANOVA and chi-square test, the significance being stated at p Results: The frequency of pregnancy anemia was 51.4%. The mean hemoglobin value of the overall study group was 8.7 ± 0.5 g/dL. The mean maternal age and weight were 28.9 ± 6.2 years and 65.3 ± 11.7 kg, respectively. Most pregnant women (83.1%) had a diet consisting of food of plant and animal origin in equal proportions. Mean of Body Mass Index (BMI) was 24.6 ± 4.6 Kg/m2 and 44.3% were overweight and obese. The co-morbidities associated were malaria and intestinal parasitosis found in 45% and 5.9% of cases, respectively. After iron treatment with Ferric Sodium EDTA, the average hemoglobin level increased to 11.2 g/dL with mean gain of 2.5 g/dL (p Conclusion: Ferric Sodium EDTA as a novel iron formulation (Hemoforce Plus Zinc®) has shown a rapid increase in hemoglobin levels in pregnant women suffering from anemia. The speedy rise in hemoglobin is related to the property of Ferric Sodium EDTA to enhance the iron absorption by inhibiting the dietary iron inhibitors. Thus, Ferric Sodium EDTA should be used as an effective and promising iron supplement in pregnant women with iron deficiency anemia.

Formulation and Evaluation of Flurbiprofen Solid Dispersions Incorporated Buccal Patches

Flurbiprofen is an anti-inflammatory drug used in treating rheumatoid arthritis and ankylosing spondylitis. The present work is aimed at overcoming the deprived solubility of flurbiprofen by solid dispersion (SD) technique. The current paper is the continuance of the published solid dispersion by considering the best final optimized formulation containing flurbiprofen drug: AQOAT AS: SLS as drug: polymer: surfactant in 1:5:2 ratios, and incorporating it into buccal patches to overcome the gastric side effect and attaining sustained drug release. In this study 15 buccal patches were formulated by adopting solvent casting technique using polymers like polyvinyl hydroxyethylcellulose (HEC), hydroxypropryl methyl cellulose E15 (HPMC E15), polyvinyl pyrrolidone (PVP), carbopol and analyzed for the drug content, drug diffusion, in-vivo dissolution and stability studies. All SD loaded patches displayed superior drug release (95% to 99.96%) over 12 h. The formulation BP14 showed excellent drug release extended over 12 h with drug release of 99.96% whereas marketed formulation which is sustained release Tablet showed 96.86% drug release within 6 h. The drug release kinetics show that the buccal patches follow zero order release kinetics with correlation coefficient (R2) ranging between 0.905-0.971 and BP14 formulation shown best R2 value. All the formulations exhibited best fit to Higuchi model with R2 ranging between 0.9911 – 0.9962 indicating drug release by diffusion process. The results conclude that buccal patches are superior alternatives for flurbiprofen that facilitates enhanced drug release for prolonged period of time in the effective management of rheumatoid arthritis.

Synthesis, characterization and pharmacological investigation of lysine and glycine conjugated amide prodrugs of (+)-ibuprofen

(+)-ibuprofen [(+)-IBN] is a Non-steroidal anti inflammatory drug (NSAIDs) that is pharmacologically active stereoisomer of racemic form of ibuprofen. Literature showed that Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen and flubiprofen, are widely provide the protective effect against the neurodegenerative conditions. But the therapeutic application of NSAIDs in the CNS disorders were limited due to their limited brain distribution across the physiological barrier, blood brain barrier (BBB).BBB is composed of tightly connected endothelial cells of brain capillaries and the surrounding astrocytes and pericytes. The compounds which are able to cross the BBB by passive diffusion are small, lipophilic and uncharged at physiological PH. This study make an attempt to synthesize the derivatives (+)-IBN by conjugating with amino acids such as glycine and lysine that produced the two amide prodrugs,(+)-IBN-G and (+)-IBN-L. The objectives of this study are to synthesize the amide prodrugs of (+)-IBN with glycine and lysine produced (+)-IBN-G, (+)-IBN-L respectively and to perform detailed study on their physical and chemical properties, distribution profile in the brain, brain targeting efficiency parameters, pharmacological activities. The compounds synthesized will act as prodrugs of (+)-IBN and after the administration the (+)-IBN was released at the desired site by enzymatic or non-enzymatic hydrolysis and synthesized prodrugs showed the enhanced brain distribution , protective against neurodegeneration, enhanced anti inflammatory activity, reduction in the gastric side effect such as ulcer formation in the stomach.

Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and improved toxicity profile.

Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti-inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2-mercaptobenzimidazole amino acid conjugates (4a-4o) and screened them for analgesic, anti-inflammatory and gastro-protective effects. The synthesized 2-mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1 H NMR and 13 C NMR spectroscopic techniques. The 2-mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti-inflammatory and gastroprotective activities, particularly with compound 4j and 4k. Most of the compounds exhibited remarkable anti-ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX-2 (PDB ID: 3LN1) and H+ /K+ -ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2-mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.

The COVID 19 Desire for Cure - Exahusting Quest for Remedy, Mutations and Cytokine Storms

With the intent to cure the elusive disease, the Corona Virus (SARS COV-2) propulsion can be thought to project to cases of neurodegenerative diseases [1]. Standard features of inflammation (redness, edema, fever, pain). The loss of function and immunological response involved in the production of specific antibodies against Aggression Agent. The inflammatory response is not always sufficient, and the process can progress to a chronic inflammation. On-steroidal anti-inflammatory drugs (NSAIDs) are now the main family of drugs used to treat Inflammation but often, they show gastric and cardiovascular side effects. This situation is an incentive towards a search for new molecules to treat Inflammation. Many plants mostly used against inflammatory processes, so they are potential sources of new bioactive molecules. Among the various chemical classes of natural bioactive products, Flavonoids - a group of polyphenolic compounds - show exceptional promise. Flavonoids are widely distributed throughout the plant kingdom and are pharmacologically important, especially for their action Inflammation and immune system [2]. This article describes various aspects of the inflammatory process and its treatment, with a special people Focus on the anti-inflammatory activity of flavonoids. And other polyphenolic antioxidants present in fruits, for example [3]. With the intent to cure the elusive disease, one may consider that the coronavirus virus eradication (SARS COV2) is projecting to cases of degenerative diseases. One might focus on suppressing the body immunity and cytokine overproduction by the much-desired curing agents [4].