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The present work aims to present two new concepts concerned with chiral separation. First, chiral separation of some enantiomeric drugs, using micelle-based liquid chromatography without any chiral selector, whether in the stationary phase or the mobile phase, was performed. The surfactants used were anionic; sodium dodecyl sulphate, and cationic; cetrimide. The studied analytes include phenyl-ephrine hydrochloride (PHR), cetirizine dihydrochloride (CTZ), and mebeverine hydrochloride (MBV). Successful separation of the enantiomers was attained, giving promising results that may cause a revolution in chiral separation, predicting the possibility of simply prepared aqueous micellar mobile phases of carrying chiral selector ability. The second motive of this work is studying the compatibility of hybrid micelle liquid mobile phases with chiral columns separating CTZ, using cellulose 1 chiral column as a model example. This study may be an environmentally safe substitute for the normal phase mode of elution that is usually applied for chiral separation consuming large amounts of hazardous organic solvents.

Objective: Mebeverine hydrochloride is an antispasmodic agent that has a direct musculotropic action on the smooth muscles of the gastrointestinal tract; especially the colon.Therefore, the current study aimed at formulating and optimizing colon targeted mebeverine hydrochloride microspheres for treatment of chronic gastrointestinal disorder. Methods: Mebeverine hydrochloride-loaded chitosan microspheres were formulated adopting emulsion cross-linking method using glutaraldehyde as a cross linking agent. A 33 Box Behnken design was utilized in formulating the microspheres and investigating the effect of different formulation factors such as drug: polymer ratio (X1), stirring speed (X2) and the surfactant concentration (X3) on particle size (Y1), the entrapment efficiency percentage (Y2) and the cumulative release percentage of mebeverine hydrochloride after 8 h (Y3). Results: The particle size and entrapment efficiency were significantly affected by tested formulation parameters. The release of mebeverine hydrochloride from optimized formula was pH dependent. In simulated gastric fluid, less than 10% of entrapped mebeverine hydrochloride was released, while, a relatively high amount of the drug (> 65%) was released in simulated colonic fluid (pH 7.4). The in vivo pharmacokinetic study revealed that the optimized formula of microspheres exhibited increased oral absorption of mebeverine hydrochloride, compared to free drug (Cmax 168.51±20.05 ng/ml vs. 126.45±29.46 ng/ml, respectively). In addition, the optimized formula exerted a remarkably higher systemic bioavailability, compared to the free drug. Conclusion: These results underscore the applicability of cross-linked chitosan microspheres as a promising carrier for colon targeted delivery of mebeverine hydrochloride for treating diseases associated with the colon such as irritable bowel syndrome.

What is known and objectives There is clear evidence for an association between irritable bowel syndrome (IBS) and visceral hypersensitivity. This clinical study aimed to assess the adjunct role of ethosuximide, an antiepileptic drug with T-type calcium channel blocking activity, in the relieving of IBS-related abdominal pain. Methods This is a prospective, 3-month, randomized and controlled study of parallel groups. Fifty outpatients who met the inclusion criteria participated in the trial. Patients were allocated randomly: 25 received mebeverine 135 mg three times daily (t.i.d), whereas the other 25 received mebeverine 135 mg t.i.d and ethosuximide 500 mg t.i.d. At baseline and 12 weeks after starting the drug, patients were evaluated by a gastroenterologist. Serum tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), faecal myeloperoxidase and faecal neutrophile gelatinase-associated lipocalin (NGAL) levels were tested before and after treatment. The Numeric Pain Rating Scale (NRS) was assessed before and after three months of therapy. Results and discussion After 12 weeks, the ethosuximide group showed a statistically and significantly greater reduction in the serum levels of TNF-α, IL-6, IL-8, faecal myeloperoxidase and faecal NGAL in comparison with the control group after the treatment. Moreover, the ethosuximide group showed a statistically significant decrease in NRS compared with the mebeverine group. What is new and conclusion Ethosuximide could be a promising adjunct to antispasmodics in the treatment of IBS patients. Trial registration identifier: NCT04217733.

OBJECTIVES To investigate the efficacy of mebeverine for nocturnal incontinence in male patients with an ileal orthotopic bladder substitute (OBS). PATIENTS AND METHODS A randomised controlled trial was carried out for adult male patients who were nocturnal incontinent. Patients were allocated to receive mebeverine 200 mg or placebo once a day in the evening for 3 months. The primary outcome was to compare the continence status between groups, assessed by the urinary domain of the Bladder Cancer Index (BCI) and pad usage. The secondary outcomes were to assess the safety of mebeverine. RESULTS There were 55 patients in the placebo group and 58 in mebeverine group who completed the follow-up. The median (interquartile range) interval between OBS surgery and starting treatment was 9 (4-13) years in the placebo group and 9 (6-13) years in the mebeverine group. The mean (SD) 3-month urinary domain score of the BCI was 70.8 (5.6) and 86.4 (14.2) in the placebo and mebeverine groups, respectively (P

Irritable bowel syndrome (IBS) is a world-wide disease prevalently in Western nations. It influences about 15% of the western populace, with a negative effect on the quality of life and furthermore on medical services costs. Anticholinergic antispasmodics are first line of treatment for discomfort or abdominal pain, particularly if unrelieved after alleviation of stoppage or antidiarrheal treatment. Otilonium bromide (OTB) is quaternary ammonium compound with action on distal GI tract as antispasmodic. It is utilized in the treatment of patients influenced by Irritable inside disorder (IBS) because of its particular pharmacokinetic and pharmacodynamic properties. OTB is poorly absorbed systematically was viable in contrast with different medications used for same purpose, for example, pinaverium bromide and mebeverine, with a good tolerability profile. The effects are long lasting, even after stopping the dosage regime for reduction of abdominal pain. In this review, an overview of mechanism of action, pharmacologic action, synthesis and particularly various analytical and bioanalytical methods are discussed. The analytical methods discussed are spectrophotometry including Near Infrared Spectroscopy (NIRS), chromatography and capillary electrophoresis methods are described with the range, limit of detection and quantification. The paper also provides details of scope of further extension of analytical methods. It was found that most of the analytical methods involves usage of toxic solvents e.g., methanol, acetonitrile, chloroform etc. posing risk to the analyst as well as environment.

Background: Selective norepinephrine-serotonin receptor inhibitors (SNRIs) such as duloxetine have already shown beneficial effects on symptoms in irritable bowel syndrome (IBS) patients. The purpose of the present investigation was to assess the efficacy of duloxetine in the symptom and quality of life improvement in diarrhea predominant-IBS (IBS-D) patients. Materials and Methods: IN a randomized, double-blind and placebo-controlled study, sixty patients diagnosed with IBS-D (ROM-IV criteria), referred to the gastrointestinal clinic of Rasoul-e-Akram Hospital of Iran university of medical sciences, randomly assigned in the treatment groups, group A: patients who received 135 mg mebeverine tablet twice a day combined with 30 mg duloxetine capsule per day and group B, who received the same regimen, except for placebo capsule once per day instead of duloxetine for twelve weeks. The assessment was performed using the IBS severity index, and IBS quality of life questionnaire (IBS-QOF) at baseline, and weeks 4, 8, and 12 after beginning the treatment. Drug adverse effects and compliance to treatment were evaluated every 2 weeks after starting the treatment. Results: Sixty patients completed the trial. The duloxetine group showed significantly greater improvement on the IBS symptoms (P < 0.001), and the IBS-QOF (P < 0.001) in comparison to the placebo group at the endpoint. Conclusions: This study showed that adding duloxetine to mebeverine is safe with good efficacy on symptoms and QOL improvement in IBS-D patients. Besides, this study showed that 12 weeks' treatment duration is significantly more effective than 4 weeks' treatment, and drug adverse effects are more prominently seen in the first 2 weeks of treatment.

Background and Aims: Irritable bowel syndrome (IBS) is a chronic relapsing disorder characterized by abdominal pain-discomfort and altered bowel habits. The IBS-diarrhoea predominant subtype (IBS-D) is defined as >25% of bowel movements representing type 6 or 7 of the Bristol Stool Form Scale. Management of IBS-D is mainly symptomatic, including lifestyle modification. Due to absence of standard treatment, multiple drugs are used. A controlled release (CR) form of mebeverine, recommended for spasmodic gastrointestinal disorders (including IBS) has recently been introduced in Indian market. We have conducted a placebo-controlled double blind randomized controlled trial [CTRI/2018/03/012897] to evaluate the effectiveness and safety of this product. Methods: 40 patients of IBS-D were recruited from medicine out-patient department (OPD) of a tertiary care hospital and randomized to two parallel groups. One received mebeverine 200 mg CR tablets twice daily for 8 weeks, while other received matching placebo. Outcome parameters were number of bowel movements per day over past 7 days (NoBM7d), severity of abdominal cramps and IBS quality of life (IBSQoL) score. Medication adherence record and treatment emergent adverse events were captured. Results: Mebeverine group showed modest but statistically significant improvement in NoBM7d, cramps and IBSQoL from baseline to 4 and 8 weeks. The changes within the placebo group were not statistically significant. Also, the intergroup differences at both 4 and 8 weeks were not statistically significant. Adherence was better in mebeverine group and both interventions were well tolerated. Conclusions: Mebeverine 200 mg CR twice daily has modest effect in IBS-D and therefore will not be a good choice for patients with severe symptoms.

Introduction: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Treatment can improve symptoms and social functioning in the patients. This study was designed to assess the effect of adding Luvos supplementation to mebeverine on improving symptoms and quality of life (QOL) in patients with diarrhea-predominant irritable bowel syndrome. Methods: Eighty patients with diarrhea-predominant IB, ages 18-65, were diagnosed by the Rome IV criteria and randomly assigned to the study. Forty patients (group A) received mebeverine (135 mg) twice a day (bid) plus Luvos®Healing Earth (1 sachet, bid). The other 41 patients (group B) received mebeverine (135 mg) bid for 4 weeks. Basic demographic data, Bristol score, symptom severity score, and QOL questionnaire were recorded at the start and completion of treatment. The data were analyzed by SPSS version 22. Results: Seventy one of the patients (35 and 36 patients in groups A and B, respectively) completed the study. The majority of the patients were young males, unmarried and highly educated. Diarrhea and QOL were both significantly improved in group A when compared to group B (P=0.036 and P=0.028, respectively). We did not find a significant difference (improvement) in abdominal pain or overall symptom score between group A (mebeverine + Luvos) compared to group B (mebeverine alone) (P=0.096 and P=0.071, respectively). Mild and tolerable adverse effects were observed in 2.8% (2/71) of the patients. Conclusion: According to our results, Luvos supplementation is safe, effective and well-tolerated in diarrhea-predominant irritable bowel syndrome patients. Further study with a larger sample size is recommended to evaluate the efficacy of this natural clay-like medicine.

The approaches to bioanalytical method development for determination of substances which contain unstable functional groups in the structure are described. The oxidation and the hydrolysis are main causes of the decomposition of substances in biological fluids. Phenolic hydroxyls contain drugs were selected as examples of oxidable compounds, glucuronides of drugs were selected as examples of hydrolysable compounds. Determination of mycophenolic acid, which contains one phenolic hydroxyl and metabolized by formation of glucuronides, in plasma was performed using high performance liquid chromatography with mass-spectrometry and tandem mass-spectrometry detection. Methyldopa, which contains two phenolic hydroxyls, in stabilized plasma was assayed by high performance liquid chromatography – tandem mass-spectrometry in the range of 0.02–3.00 μg/ml. Concentrations of desmethyl mebeverine acid, which contains in the structure one phenolic hydroxyl and metabolized by formation of phenolic glucuronide, was measured simultaneously with mebeverine acid in the range of 10–2000 ng/ml. The influence of the ion source conversion of glucuronides on the quantitative determination of the substances was studied in the initial part of methods development. The next, selection of anticoagulants based on the study of short-term stability and freeze/thaw stability of the analytes and back conversion of their glucuronides was performed. The combination of anticoagulant K3EDTA and the antioxidant solution containing a mixture of ascorbic acid, sodium sulfite and sodium hydrogen carbonate in the concentrations of 5.0 %, 0.2 % and 2.4 %, respectively, was used to prevent degradation of methyldopa.

Gastrointestinal tract (GIT) functional disorders are one of the most urgent problems in modern gastroenterology, which is due to the widespread nature of this pathology and the problems associated with it. They form a group of heterogeneous (different in nature and origin) clinical states, manifested by various symptoms and disorders of gastrointestinal tract functions, and are not accompanied by structural, metabolic or systemic changes. According to the results of numerous epidemiological studies, up to 50-60 % of adults and up to 30-40 % of children who apply to gastroenterologists suffer from various functional disorders in the digestive system. The World Health Organization (WHO) states: over the past 60 years, the incidence of these disorders has increased 24-fold. Aim. To analyze the range, prices and availability indicator Ca.s. of anesthetic drugs in Ukraine during 2014-2016, and to determine the dynamics of these characteristics for the study period. Results. In 2016 there were 9 INN on the Ukrainian pharmaceutical market , 69 trade names (TN) of drugs were detected. The structural analysis of antispasmodics assortment (2016) showed the largest TN assortment is characteristic of INN: Drotaverin – 30 TN; Simethicone – 16 TN; Papaverine – 10 TN. Medicines are presented on the market in a wide assortment and in an affordable price range, which enables the physician to choose a drug based on its effectiveness and safety. Spasmolytics are presented in a variety of forms: tablets, capsules, syrups, rectal suppositories, oral drops (in the form of emulsions), and solutions / suspensions for the preparation of injections. The most common form of release in this pharmacological group is the pill. In the process of analysis the antispasmodics drugs assortment during the period of 2014-2016, a tendency was observed in the decreased number of foreign manufactured medicines, but there was a slight increase in domestic drug production. By the indicator of economic availability, most generic drugs used for treatment functional disorders in gastrointestinal tract, are highly available. In most cases, imported medicines are in average availability. Conclusions. During the three years studies, the number of domestic generic drugs increased, which are more accessible to Ukrainian consumers, and the number of imported medicines is slightly decreased. The range of prices varied from low to high, and this gave the opportunity to individually choose drugs based on the active ingredients, dosage forms and prices. It ranged from 4.35 to 266.31 UAH, and within the limits of one INN Drotaverin. The study of antispasmodic drugs availability allowed us to establish the vast majority of SLS is represented by highly available medicines, and only some of the INNs are mediated by spasmolytic action medications of mebeverine, drotaverin and pinaverium bromide.

The first use of a green method of analysis using diatom for trace determination of mebeverine in its pharmaceutical formulation and human serum based on its great properties such as high surface area, hydrophilicity, and adsorption. in addition to diatom requires no chemical modification. Characterization of Diatom using FTIR showed bands corresponding to AlMgOH, Si-O-Al, SiOH, and OH, while XRD showed that diatom is amorphous containing silica of quartz crystal shape, SEM revealed that diatom has porous surface. Cyclic Voltammetry of the modified electrode revealed that the modified electrode has higher surface area and greater adsorption. Mebeverine hydrochloride (MV.HCl) was determined based on 5% diatom modified carbon paste electrode 5% (w/w)DA/CPE as a sensor with LOD and LOQ of 1.80×10−9 and 6.00×10−9 respectively. Then, the modified electrode was successfully applied for the trace determination of MV.HCl in different pharmaceutical preparations; “Coloverin A”, “Colona” and “Colofac” tablets without interferences from excipients and co-formulated drugs. The achieved detection limit in human serum was 8.0×10−9 M. The described adsorptive anodic stripping voltammetric method is reliable, simple, and sensitive enough for assay of MV.HCl in real plasma samples, pharmacokinetic studies, quality control and assurance of the drug in industry and in clinical laboratories.

Selective myotropic spasmolytics are the most effective modern correction means for pain at irritable bowel syndrome. Currently various drugs of mebeverine hydrochloride are represented in the domestic market, the dosage of the active substance in which is identical but they are produced by various technologies. We established that in patients with the irritable bowel syndrome administration of the drug Niaspam (Sun Pharmaceutical Industries Ltd.) at standard dosages for 2 weeks showed high effectiveness in arresting pain syndrome and intestinal dyskinesias. Niaspam statistically reliably reduces the relative intensity of intestinal contractions, normalizes the contraction rythmicity but effective predominantly in lower parts of the gastrointestinal tract. Peculiarities of the production technology allow gradual mebeverine release from the capsule, which is extremely important in therapy of intestinal dyskinesias.

A novel electrochemical sensor for the selective determination of mebeverine hydrochloride (MEB) in drug substance, products, and human plasma was introduced. The prepared nanoparticle sensor was based on a carbon paste electrode chemically modified with silica and gold nanoparticles. The surface morphology of the modified electrode was characterized by scanning electron microscope. Several parameters such as pH, scan rate, and accumulation time were optimized in order to determine the best conditions for analysis. A good linear response was obtained in the range of 4.0 × 10−8−1 × 10−5 mol L−1 with detection limit of 1.5 × 10−9 mol L−1. The obtained results are in good agreement with those obtained by official method. The method was applied for determination of mebeverine hydrochloride in different pharmaceutical dosage forms containing MEB alone or in mixtures with sulpiride or chlordiazepoxide as well as in human plasma. The developed method was simple, rapid, economic, and challenging to green chemistry.

Thin film of a moleculary imprinted polymer (MIP) based on electropolymerization method with sensitive and selective binding sites for mebeverine (MEB) was developed. This film was cast on pencil graphite electrode (PGE) by electrochemical polymerization in solution of pyrrole (PY) and template MEB via cyclic voltammetry scans and further electrodeposition of silver nanoparticles (AgNPs). Several parameters controlling the performance of the silver nano particles MIP pencil graphite electrode (AgNPs-MIP-PGE) including concentration of PY(mM) concentration of mebeverine (mM), number of cycles in electropolymerization, scan rate of CV process (mV. s−1), deposition time of AgNPs on to the MIP surface (s), stirring rate of loading solution (rpm), electrode loading time (min), pH of Britton–Robinson Buffer (BRB) solution were examined and optimized using multivariate optimization methods such as Plackett–Burman design (PBD) and central composite design (CCD). Two dynamic linear ranges of concentration for the MIP sensor were obtained as. 1 × 10 −8 to 1 × 10 −6 and 1 × 10 −5 to1 × 10−3 M with the limit of detection (LOD) of 8.6 × 10 −9M (S/N = 3). The proposed method was successfully intended for the determination of MEB in real samples (serum, capsule). The sensor was showed highly reproducible response (RSD 1.1%) to MEB concentration. Keywords: Molecularly imprinted polymer, Electrochemical sensor, Mebeverine, Multivariate optimization, Silver nanoparticle

In this study three new spectrophotometric methods have been developed and validated for simultaneous determination of ternary mixture of metronidazole (MET), diloxanide (DLX) and mebeverine HCl (MEB) without prior separation steps. The newly introduced methods consisted of several steps utilizing either zero order or ratio spectra without the need for derivatization steps. The developed methods are called area under the curve ("AUC"), modified absorption factor (MAFM) and modified amplitude center (MACM) spectrophotometric methods. Selectivity and validity of the methods were checked by using different synthetic mixtures and by analysis of their combined dosage form where low standard deviation values and good percentage recoveries were obtained. Additionally, methods linearity, accuracy and precision were determined following United States Pharmacopoeia (USP) recommendations. The obtained results were found to agree with the reported ones when they were statistically compared using One Way ANOVA test. These methods are easily applied during drug quality control studies and in laboratories lacking the facilities of chromatographic methods of analysis. Data manipulation steps are very simple, hence these methods can be considered as time and money saving methods comparing to chromatographic methods of analysis.

Metabolism studies with selected test substances have shown that a model on the basis of the incubated hen's egg is suitable as a supplement to animal experimentation. Because of its 3,4-dimethoxyphenyl structure veratric acid (3,4-dimethoxybenzoic acid), a known human metabolite of mebeverine, was chosen as model substance for the present investigations and the parent compound as well as 4-hydroxy-3-methoxybenzoic acid were identified as main metabolites. The absence of 3-hydroxy-4-methoxybenzoic acid lets conclude that the O-demethylation takes place exclusively at the p-methoxyl function. In addition, 3,3',4,4'-tetramethoxy-l-ornithuric acid (2,5-bis-(3,4-dimethoxybenzoylamino)pentanoic acid) and its O-desmethyl derivative could be characterized as further metabolites. So far an amino acid conjugate has not been described after veratric acid administration in a vertebrate. There were no indications for the appearance of 3,4-dihydroxybenzoic acid in the veratric acid metabolism. This was confirmed by corresponding studies having the isomeric guaiacol acids as precursor. Furthermore, it could be proved that in ovo the O-methylation of 3,4-dihydroxybenzoic acid occurs regioselective at the m-hydroxyl group. The results which broaden the knowledge on the metabolic fate of veratric acid are discussed in comparison with those in mammals. The metabolites were identified by GC-MS, ESI-HRMS and LC/ESI-MS/MS. The structure of the synthesized reference substance was confirmed by MS, (1)H and (13)C NMR spectral data.

Ethnopharmacological relevance Mentha longifolia , Cyperus rotundus and Zingiber officinale are widely used in Iraqi traditional medicine for the treatment of multiple gastrointestinal diseases. The aim of this study was to examine the effectiveness of a combination of three herbal agents that are widely used in folk medicine in Iraq for the treatment of patients with irritable bowel syndrome (IBS). Materials and methods A prospective randomised clinical study was carried out on 40 patients of both sexes between 25 and 60 years of age who had been diagnosed with IBS for 5–10 years. The patients were allocated to one of two groups, each consisting of 20 patients. Group A was treated with mebeverine, and Group B was treated with a capsule containing a combination of the following three herbs prepared as fine powders: Mentha longifolia , Cyperus rotundus and Zingiber officinale . IBS symptoms were assessed before and after 8 weeks of treatment. Results Treatment of IBS patients with the herbal combination resulted in improvements in all of their IBS symptoms after 8 weeks, as revealed by increase in their individual symptom scores and in their mean total improvement percentages. These results were comparable to those produced by the standard agent mebeverine. Conclusion Patients with IBS showed significant improvements in their IBS symptoms after 8-weeks of treatment with the herbal combination and did not report any adverse effects during their treatment. These results support the efficacy and safety of the herbal combination for the treatment of IBS.

A new method for the analysis of mebeverine hydrochloride (MEB) has been developed using a two-chip device. The method is highly selective, sensitive, rapid and consumes minute amount of reagents. The developed method is free of interference from the degradation products of MEB and from common ingredients present in pharmaceutical formulations. The limit of detection was 0.043 µg/mL, and the limit of quantification was 0.138 µg/mL. The short analysis time per sample (20 s) allowed a large number of analyses to be performed within a very short time. Various samples were analyzed, including two different pharmaceutical formulations and a uniformity of content analysis for 20 tablets from a known batch and two biological samples at different concentrations. In addition, the method was compared with a validated high-performance liquid chromatography (HPLC) method and the results clearly indicated the suitability of the developed method for routine analyses. A new mechanism for the tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)3 (2+) )-peroxodisulfate (S2 O8 (2-) ) chemiluminescence (CL) system has also been proposed. The mechanism is based on photoinduced oxidation of Ru(bpy)3 (2+) to Ru(bpy)3 (3+) via the formation of Ru(bpy)3 (2+) * upon irradiation with visible light. S2 O8 (2-) then oxidizes Ru(bpy)3 (2+) * to Ru(bpy)3 (3+) and the analyte subsequently reduces the resultant Ru(bpy)3 (3+) to Ru(bpy)3 (2+) *, which then produces the CL signal.

Quality by design is an important concept, but only limited research has been invested in concentrated pharmaceutical suspensions. A need exists for novel analytical tools to thoroughly characterize the drug as well as its aggregated particle structure in suspension. This work focuses on lipid-based pharmaceutical suspensions for filling of capsules. A rheolog- ical approach, namely the fractal concept of flocculation, is introduced to the pharmaceutical field. The model drug mebeverine hydrochloride was first physicochemically analyzed. A special aim was to study the surface energy profiles using inverse gas chromatography as a critical characteristic for the suspension's rheological behavior. Suspensions were manufactured in lab- oratory process equipment while applying different homogenization speeds. Flow curves of the final suspensions were measured using a cone-and-plate rheometer. As a result, surface energy profiles revealed differences from one mebeverine lot to another. Different homogenization in- tensities greatly affected the viscosity and the Mooney model was able to predict experimental values as a function of the drug volume fraction. The fractal concept of flocculation charac- terized mebeverine in suspension and a slight increase of fractal dimension was noted when homogenization speed was increased. It was concluded that the introduced concepts have large potential for designing quality into concentrated pharmaceutical suspensions. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:994-1007, 2013

Background: Irritable bowel syndrome (IBS) is a chronic, episodic functional gastrointestinal disorder characterized by abdominal pain / discomfort and altered bowel habits. Though it is considered as a functional disorder, the burden of the disease to the patients is very high and the quality of life becomes miserable. Currently available IBS therapies are mainly symptom oriented and have limited efficacy. Various studies had done so far which provide a clear rationale for the use of Synbiotic in this disorder. The objective of the study includes, this study was planned to compare the efficacy of Mebeverine + Synbiotic combination with Mebeverine and Synbiotic monotherapy in patients with diarrhoea predominant irritable bowel syndrome. Methods: The study was done in Department of Medical Gastroenterology, Rajiv Gandhi Government Hospital, Chennai for duration of one year. Patients with Irritable Bowel Syndrome (diarrhea predominant type), diagnosed within 1 year and attending outpatient department were taken. A randomized, Phase III, prospective, interventional, open label, outpatient, comparative study design was done. A total of 60 patients divided into 3 groups were finally selected for the study purpose. Results: Twelve weeks after completion of active drug therapy, the Mebeverine + Synbiotic combination improved all the symptoms of IBS except abdominal pain. Further it was evident that combination therapy had significant remission in stool frequency and consistency when compared with other groups. Conclusions: Combination of Mebeverine + Synbiotic is more effective in improving most of the troublesome symptoms in patients with diarrhea predominant irritable bowel syndrome than other therapies and also in maintaining remission, in terms of frequency and consistency of stools.

In the present work, bar adsorptive microextraction using miniaturized devices (7.5 × 3.0 mm) coated with suitable sorbent phases, combined with microliquid desorption (100 μL) followed by high-performance liquid chromatography with diode array detection (BAμE-μLD/HPLC-DAD), is proposed for the determination of trace level of six pharmaceuticals (furosemide, mebeverine, ketoprofen, naproxen, diclofenac and mefenamic acid) in environmental water and urine matrices. By comparing ten distinct sorbent materials (five polymeric and five activated carbons), the polymer P5 proved to be the most suitable to achieve the best selectivity and efficiency. The solvent volume minimization in the liquid desorption stage demonstrated remarkable effectiveness, being more environmentally friendly, and simultaneously increased the microextraction enrichment factor two-fold. Assays performed through BAμE(P5, 0.9 mg)-μLD(100 μL)/HPLC-DAD on 25 mL of ultrapure water samples spiked at the 4.0 μg/L level yielded average recoveries ranging from 91.4% (furosemide) to 101.0% (ketoprofen) with good precision (RSD < 10.6%), under optimized experimental conditions. The analytical performance showed convenient detection limits (25.0 – 120.0 ng/L), good linear dynamic ranges (0.1 to 24.0 μg/L), appropriate determination coefficients (r 2 > 0.9983), and excellent repeatability through intraday (RSD < 10.4%)) and interday (RSD < 10.0%) assays. By using the standard addition methodology, the application of the present analytical approach on environmental waters and urine samples revealed the occurrence of trace levels of some pharmaceuticals. The solvent minimization during the back-extraction step associated with the miniaturization of BAμE devices proved to be a very promising analytical technology for static microextraction analysis.

The applicability of two-phase liquid-phase micro-extraction (LPME) in porous hollow polypropylene fiber for the sample preparation and the stereoselective pharmacokinetics of mebeverine (MEB) enantiomers (an antispasmodic drug) in rat after intramuscular administration were studied. Plasma was assayed for MEB enantiomer concentrations using stereospecific high-performance liquid chromatography with ultraviolet detection after a simple, inexpensive, and efficient preconcentration and clean-up hollow fiber-based LPME. Under optimized micro-extraction conditions, MEB enantiomers were extracted with 25 µl of 1-octanol within a lumen of a hollow fiber from 0.5 ml of plasma previously diluted with 4.5 ml alkalized water (pH 10). The chromatographic analysis was carried out through chiral liquid chromatography using a DELTA S column and hexane–isopropyl alcohol (85:15 v/v) containing 0.2% triethylamine as mobile phase. The mean recoveries of (+)-MEB and (−)-MEB were 75.5% and 71.0%, respectively. The limit of detection (LOD) was 3.0 ng/ml with linear response over the concentration range of 10–2500 ng/ml with correlation coefficient higher than 0.993 for both enantiomers. The pharmacokinetic studies showed that the mean plasma levels of (+)-MEB were higher than those of (−)-MEB at almost all time points. Also, (+)-MEB exhibited greater tmax (peak time in concentration–time profile), Cmax (peak concentration in concentration–time profile), t1/2 (elimination half-life), and AUC0–240 min (area under the curve for concentration versus time) and smaller CL (clearance) and Vd (apparent distribution volume) than its antipode. The obtained results implied that the absorption, distribution, and elimination of (−)-MEB were more rapid than those of (+)-MEB and there were stereoselective differences in pharmacokinetics. Chirality 24:634–639, 2012. © 2012 Wiley Periodicals, Inc.

Background/Aims Antispasmodics including otilonium bromide (OB) are recommended to treat irritable bowel syndrome (IBS). However, reports about OB experience in Asia is sparse. The purpose of present study was to provide the efficacy of OB in treating Asian IBS patients. Methods Overall, 117 IBS patients meeting Rome II criteria were enrolled in an 8-week, double-blind, active-controlled and single center trial. Randomized participants received either OB 40 mg or mebeverine 100 mg 3 doses daily. The primary endpoints were to evaluate the net changes of abdominal pain/discomfort frequency score (APDFS) and safety profile, while the secondary endpoints were to assess the changes in abdominal pain/discomfort intensity, flatulence, abdominal bloating, satisfied stool frequency etc. Results Finally, 49 OB and 52 mebeverine subjects were eligible for efficacy analysis. Compared to baselines in per protocol populations, the reduced APDFSs in OB and mebeverine were 0.55 ± 1.20 (P = 0.011) and 0.37 ± 1.11 (P = 0.042), respectively, to show similarly reduced scores. The most reported side effects included dry mouth, nausea and dizziness. Besides, the improved APDFSs at 4th week visit, final alleviations in abdominal pain intensity, flatulence, abdominal bloating and satisfied stool frequency with global assessments filled by both patients and investigators were significantly achieved by both treatments, and OB was not inferior to mebeverine in treating these parameters. Conclusions In Orientals, OB is as effective as mebeverine for alleviating IBS symptoms in terms of abdominal pain, flatulence, abdominal bloating etc. However, obvious side effects are also observed. A large-scaled trial and post-marketing surveillance are recommended to confirm its efficacy and safety.

A simple, economic, and time-efficient stability-indicating, reverse-phase ultra-performance liquid chromatographic (RP-UPLC) method has been developed for analysis of mebeverine hydrochloride in the presence of both impurities and degradation products generated by forced degradation. When mebeverine hydrochloride was subjected to acid hydrolytic, oxidative, base hydrolysis, photolytic, and thermal stress, degradation was observed only in base hydrolysis. The drug was found to be stable to other stress conditions. Successful chromatographic separation of the drug from impurities formed during synthesis and from degradation products formed under stress conditions was achieved on a Waters Acquity C18, 50 mm x 2.1 mm, 1.7 µ particle size column, UV detection at 225 nm and a gradient elution of orthophosphoric acid and acetonitrile as the mobile phase. The method was validated for specificity, precision, linearity, accuracy, and robustness and can be used for quality control during manufacture and for assessm...

Background The 5-HT3 receptor antagonists are known to be effective for the treatment of diarrhea-predominant irritable bowel syndrome (IBS), but not widely used yet. The aim of this study was to compare the efficacy and safety of ramosetron, a 5-HT3 receptor antagonist, and mebeverine in male patients with IBS with diarrhea (IBS-D). Methods This study was performed in a multicenter, randomized, open-label design. Data of 343 male patients with IBS-D who were randomized to either a 4-week treatment of ramosetron 5 μg once daily or a 4-week treatment of mebeverine 135 mg three times daily were analyzed by the intent-to-treat analysis. The primary efficacy parameter was the proportion of patients with adequate relief of IBS symptoms at the last week of treatment. The secondary endpoints were changes in each symptom score and the safety profiles. Key Results The responder rates for global IBS symptoms, abdominal pain/discomfort and abnormal bowel habits in the ramosetron and mebeverine groups significantly increased during the treatment period. The severity scores of abdominal pain/discomfort and urgency, the stool form score, and the stool frequency in both treatment arms were significantly reduced, compared with the baselines. There were no significant differences in the responder rates (37%vs 38% on ITT analysis) and adverse event profiles between the ramosetron and mebeverine groups. Neither severe constipation nor ischemic colitis was reported by ramosetron-treated patients. Conclusions & Inferences Ramosetron 5 μg once daily is as effective as mebeverine three times daily in male patients with IBS-D.

Performance of partial least squares regression (PLSR) is enhanced in the presented work by three multivariate models, including weighted regression PLSR (Weighted-PLSR), genetic algorithm PLSR (GA-PLSR), and wavelet transform PLSR (WT-PLSR). The proposed models were applied for the stability-indicating analysis of mixtures of mebeverine hydrochloride (meb) and sulpiride (sul) in the presence of their reported impurities and degradation products. The work introduced in this paper aims to compare these different chemometric methods, showing the underlying algorithm for each and making a comparison of analysis results. For proper analysis, a 6-factor, 5-level experimental design was established resulting in a training set of 25 mixtures containing different ratios of the interfering species. A test set consisting of 5 mixtures was used to validate the prediction ability of the suggested models. Leave one out (LOO) and bootstrap were applied to predict number of PLS components. The GA-PLSR proposed method was successfully applied for the analysis of raw material (test set 101.03% ± 1.068, 101.47% ± 2.721 for meb and sul, respectively) and pharmaceutical tablets containing meb and sul mixtures (10.10% ± 0.566, 98.16% ± 1.081 for meb and sul).

Sewage effluents are widely recognised as the main source of emerging contaminants, such as endocrine disrupting chemicals (EDCs) and pharmaceuticals in surface waters. A full-scale granular activated carbon (GAC) plant has been installed as an advanced technology for the removal of these contaminants, in a major sewage treatment works (STW) in South-West England as part of the UK National Demonstration Programme for EDCs. This study presented for the first time, an assessment of the impact of a recently commissioned, post-tertiary GAC plant in the removal of emerging contaminants in a working STW. Through regular sampling followed by solid-phase extraction and analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS), a significant reduction in the concentrations of steroidal estrogens was observed (>43-64%). In addition, significant reductions were observed for many of the pharmaceutical compounds such as mebeverine (84-99%), although the reduction was less dramatic for some of the more widely used pharmaceuticals analysed, including carbamazepine and propranolol (17-23%). © 2010 Elsevier B.V.