Racecadotril Research Articles

Multivariate Optimization of Chromatographic Conditions for Rapid Simultaneous Quantification of Antidiarrheal Drugs in Formulation Using Surface Response Methodology

A combination of antibiotics and antiprotozoal and antisecretory medicines has been prescribed for the treatment of diarrhea. A rapid, reproducible liquid chromatographic procedure was established for the concurrent analysis of metronidazole (MET), ofloxacin (OFL), and racecadotril (RAC) in suspension. The Box–Behnken design, a full factorial multivariate optimization technique, was utilized to optimize chromatographic parameters with fewer runs. The separation of MET, OFL, and RAC was accomplished within 3.2 min, using a Zorbax C18 high-performance liquid chromatography column with a simple mobile phase comprising acetonitrile (55 vol.%): methanol (10 vol.%):20 mM phosphate buffer (35 vol.%, pH 6, regulated with ortho-phosphoric acid). The mobile phase was pumped in the isocratic mode at a rate of 1.4 mL/min at ambient temperature. Analytes were monitored by adjusting the wavelength at 295 nm for MET and OFL and 231 nm for RAC. Validation of the proposed HPLC method exhibited linearity in the concentration of 20–250 µg/mL, 10–150 µg/mL, and 5–80 µg/mL for MET, OFL, and RAC respectively, along with an excellent regression coefficient (r2 > 0.999). The accuracy and precision of the chromatographic procedure were also evidenced by the low percent relative error and relative standard deviation. A Pareto chart developed by the two-factor interaction (2FI) study confirmed that the method was robust, as the slight variation in a single factor had no significant influence on the assay outcomes. Lastly, the developed HPLC process was utilized for the concurrent quantification of MET, OFL, and RAC in liquid oral preparation. Furthermore, when the assay results were compared to the described techniques, it was discovered that there was no significant difference in the accuracy and precision of the results. Hence, the developed rapid HPLC method could be employed for the quality control study of a preparation comprising of MET, OFL, and RAC in industries and regulatory authority laboratories.

Enhancement of dissolution rate of racecadotril by liquisolid compact technology

The current investigation was used to improve the rate of dissolution of an anti-diarrheal drug i.e., racecadotril (RT) at low pH conditions (i.e., in the stomach) by reducing the water secretion and electrolyte in to the intestine by liquisolid tablets. Different formulations (liquisolid) were prepared using Avicel PH 102 as a carrier. Aerosil 200 as a coating material and sodium starch glycolate used as a disintegrant. Polyethylene glycol 200 was used as a non-volatile vehicle to dissolve the drug. FTIR, DSC, XRD and dissolution studies were conducted to characterise liquisolid tablets. Characterisation studies indicated that no interactions between carrier and drug. Solid state characterization had shown a reduction in crystallinity that further supports increment in solubility and dissolution. The optimised formulation showed a significant increase in dissolution i.e., 99.54±0.62% in 30 min compared to directly compressible tablets (38.47±0.26%). The % dissolution efficiency of racecadotril liquisolid tablets 76.86% compared to marketed tablet (27.56%) and conventional direct compression tablet (17.11%). Significant reduction in mean dissolution time of racecadotril from liquisolid tablets (6.84 min) compared to direct compression tablet (44.57 min), indicating faster release of drug and faster onset of action. Formulation of liquisolid tablets could enhance solubility, dissolution and bioavailability of racecadotril.

Improvement of bioavailability of poorly soluble racecadotril by solid dispersion with surface adsorption method: A case study

Introduction: Biopharmaceutics classification system class II drugs show unpredictable bioavailability based on their solubility. Unfortunately, very few products were manufactured by this technique owing to their poor flowability and stability. The objective of the current investigation was used to improve the flowability by surface solid dispersion (SSD; SD with surface adsorption technology) and improve the absorption of racecadotril (RT) under low pH conditions (i.e., in stomach) to show anti-diarrheal effect by reducing water and electrolyte secretion into the intestine. Materials and Methods: SSDs and physical mixtures (PMs) were prepared using various ratios of hydrophilic carriers (polyethylene glycol 4000, polyethylene glycol 6000, and Gelucire 50/13) and an adsorbent (lactose monohydrate). Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry , and dissolution studies (in vitro) were conducted to characterize SSDs and PMs. Results: Phase solubility curves represent AL type, indicating that the solubility of drug linearly increased with an increase in the concentration of carrier. Characterization studies indicated that no interactions between carrier and drug. Solid-state characterization showed a reduction in crystallinity that further supports increment in solubility and dissolution. The optimized formulation (SDG4) showed 99.84 ± 1.5% drug release in 15 min compared to RT plain drug (11.95 ± 1.72%). In vivo bioavailability studies of SDG4 revealed a significant (P < 0.05) increase in Cmax 65.38 ± 1.34 µg/mL (1.75-fold) with increased relative bioavailability (180.22-fold) against the RT plain drug. Conclusion: Formulation of SD with surface adsorption method could enhance solubility, dissolution, and bioavailability of RT.

Influence of montmorillonite powder combined with racecadotril granules on serum IL-2, IL-6, IL-10 and hs-CRP levels in children with rotavirus enteritis

Objective To investigate the effect of montmorillonite powder combined with racecadotril granules on serum levels of interleukin-2(IL-2), interleukin-6(IL-6), interleukin-10 (IL-10) and high-sensitivity C-reactive protein (hs-CRP) in children with rotavirus enteritis. Methods From June 2014 to July 2016, 76 children with rotavirus enteritis in the People′s Hospital of Pujiang County were selected and randomly divided into control group and study group according to the digital table, with 38 cases in each group.The two groups were given basic treatment after admission, on the basis, the control group was treated with montmorillonite powder, and the study group was treated with montmorillonite powder combined with racecadotril granules.The two groups were treated for 3 days.The clinical efficacy, clinical symptoms(stool, stool frequency, dehydration, vomiting, fever) recovery time, serum IL-2, IL-6, IL-10 and hs-CRP levels at admission and after treatment, and the incidence of adverse reactions were statistically compared between the two groups. Results The clinical efficacy of the study group(mild constipation, rash, nausea) was better than the control group[19 cases(50.00%) vs.11 cases(28.95%), 16 cases(42.11%) vs.15 cases(39.47%), 3 cases(7.89%) vs.12 cases(31.58%)], the difference was statistically significant(Z=2.358, P 0.05). After treatment, the serum levels of IL-2 and IL-10 in the study group were higher than those in the control group, the serum levels of IL-6 and hs-CRP were lower than those in the control group, the differences were statistically significant(t=5.545, 7.705, 7.090, 10.352, all P 0.05). Conclusion Montmorillonite powder combined with racecadotril granules in the treatment of rotavirus enteritis can effectively relieve the clinical symptoms, improve the serum inflammatory factors level, reduce the inflammatory reaction in vivo, improve the therapeutic effect and has high safety. Key words: Montmorillonite powder; Racecadotril granules; Rotavirus enteritis; High-sensitivity C-reactive protein; Interleukin; Safety

STABILITY INDICATING HPLC-MS/UV METHOD FOR DETERMINATION OF RACECADOTRIL FROM BULK AND FORMULATION

The present work was focused on the development of rapid, specific and novel stability indicating high performance liquid chromatographic method for determination of racecadotril (RAC) in bulk and capsule formulation. The drug and formulation were subjected to hydrolysis (acidic, alkaline and neutral), oxidative and thermal stress, as per ICH guidelines Q1A (R2). Degradation products of RAC formed under various stress conditions were well separated using a mobile phase containing acetonitrile and water (60:40 V/V) with 0.5% formic acid. Quantification was performed using RP C18 column with the detection wavelength of 230 nm.The method was considered linear in the concentration range of 5-100 μg mL−1 for RAC. Limit of detection and quantitation was found to be 0.15 and 0.45 μg mL−1 respectively. Identification of major stress degradation products was performed using qudrupole electrospray ionization mass spectroscopy (ESI-MS) in positive mode. RAC was found to be very unstable under basic condition and is converted into 2-(3-(acetylthio)-2-benzylpropanamido) acetic acid and 2-benzyl-N-(2-hydroxyvinyl) acrylamide. The drug is more stable at neutral pH as compared to acidic and oxidative stress. Under acidic conditions, benzyl 2-(2-benzyl-3-mercaptopropanamido) acetate is the probable degradation product. A stability indicating HPLC method was developed for quantitation of RAC. A strict control should be exerted on the level of basic impurities in formulations.

Hospital Based Prospective Observational Study to Audit the Prescription Practices and Outcomes of Paediatric Patients (6 months to 5 years age group) Presenting with Acute Diarrhea.

Diarrhea is a leading killer of children, accounting for 9% of all deaths among under-five children worldwide. WHO protocol deviation in management of diarrheas in children is likely due to various reasons. To study the prescription practices, regarding adherence to WHO protocol and deviations, in the management of acute diarrhea in children presenting at a tertiary care hospital and its impact on the outcome. This was a prospective observational hospital based study at a tertiary care carried out over a 12-month period including all cases of acute diarrhea (defined as 3 or more loose stools in last 24 hours) in children belonging to the age group of 6 months to 5 years. Patients were followed up on day 3,7,14 and 28 from the day of presentation. Software SPSS Version 17.0 was used for analysis. Correlation regression analysis was used to study predictiveness of different variables affecting outcome. In this study, 447 children aged between 6 months and 5 years were enrolled, of which 45 cases were lost in follow-up and excluded. The median age was 14 months. Some deviation from WHO protocol was noted in 78.4% of the cases. Most common deviations from WHO protocol were addition of probiotics (78.1% of cases) and addition of race cadotril (15.9% of cases). Inadvertent use of antibiotics in diarrhea was noted in 12.2% of cases. Presence of fever was strong predictor for use of antibiotics. Cases of early recovery within 3 days of presentation were higher in WHO protocol deviation group. Use of probiotics had statistically significant association with early recovery. In diarrhea management, WHO protocol deviation is common. Probiotics are likely to help in early recovery.

Sa1790 Comparative Clinical Studies Between Racecadotril and Loperamide or Saccharomyces Boulardii in Adult Patients With Acute Diarrhea

that oral HBB has a fast onset of action, and relief of cramping gastrointestinal pain can be expected as early as 15 min after intake of 20 mg HBB (=two Buscopan® tablets). REF: 1Schaefer E, Ewe K (1990) Fortschr Med 108 (25), 488; 2Mueller-Lissner S et al. (2006) Aliment Pharmacol Ther 23, 1741; 3Ge Z et al. (2011) Int J Clin Pharmacol Ther 49 (3), 198; 4Lacy BE et al. (2013) Scand J Gastroenterol 48 (8), 926; 5Mueller-Lissner S et al. (2011) Pharmacol Pharm 2, 82

Development and Validation of a Stability-Indicating RP-HPLC Method for Analysis of Racecadotril in Pharmaceutical Dosage Forms

A simple stability-indicating RP-HPLC method has been developed and validated for the determination of Racecadotril (RAC) in pharmaceutical dosage forms. The mobile phase consisting of methanol and tetra butyl ammonium hydrogen sulphate (80: 20, v/v) was used using isocratic elution with UV detection at 230 nm. The method showed good linearity for RAC in the 5-120 µg/mL range being the square of the correlation coefficient greater than 0.999. The limit of quantitation (LOQ) and limit of detection (LOD) were found to be 0.87527 and 0.28884 µg/mL respectively. The robustness was also evaluated by variations of mobile phase composition, flow rate and detection wavelength. The forced degradation kinetic study of Racecadotril by using HCl (0.1 M), NaOH (0.01 M), H2O2 (3%v/v), thermal (80±2 °C), hydrolysis and UV radiation (365 nm) were observed to be very specific. Finally the applicability of the method was evaluated in commercial dosage form analysis as well as in stability studies.

Racecadotril Efficacy in the Symptomatic Treatment of Adult Acute Diarrhoea: A Systematic Review and Meta-Analysis

The efficacy of racecadotril (RC), an intestinal antisecretory drug acting via an enkephalinase inhibition, was reviewed in paediatric acute diarrhoea but not yet in adults. Objective: To estimate the effectiveness of RC in the symptomatic treatment of acute diarrhoea in adults. Data Sources: A systematic review of MedLine, Cochrane Controlled Trials Register, DARE, and Embase (up to November 2013). Additional studies were identified by contacting clinical experts and the manufacturer. Study Selection and Appraisal: Randomized Controlled Trials performed in adults suffering from acute diarrhoea using RC in one treatment arm. Independent extraction of articles using predefined data fields, and methodological quality measurement assessment. All randomised trials performed in adults suffering from acute diarrhoea with RC as the studied group. Statistics: The main efficacy endpoint was diarrhoea duration defined as time to recovery compared between groups by survival techniques and converted into hazard ratio (HR). We exclusively used a random-effect meta-analytic model. Constipation proportion was the main safety endpoint, evaluated between treatments by the Relative Risks (RR). Results: Twelve randomised trials (2619 patients) met inclusion criteria. Duration of diarrhoea was much shorter in the RC group, the proportion of patients having recovered at any time of the treatment period was 65% higher in the RC group, compared with placebo (HR = 1.65 [1.38-1.97], p p = 0.24, n = 1618). The proportions of constipated patients were similar in the RC and placebo groups 0.95 [0.24-3.68], p = 0.97), however, about 3 times more constipated patients were found in the loperamide group compared with the RC group (RR = 0.34 [0.22-0.51], p to placebo, RC is characterized by a clinically relevant earlier remission of diarrhoea. When compared to loperamide, diarrhoea duration was similar, however, significantly fewer secondary constipation adverse effects were observed.

Quality by design (QbD) approach for developing agglomerates containing racecadotril and loperamide hydrochloride by crystallo-co-agglomeration

This research presents the use of experimental design, optimization and multivariate techniques to investigate the root-cause of agglomerates containing two drugs [i.e. racecadotril (RCD) and loperamide hydrochloride (LPM)]. The influence of various excipients and processing conditions on formation of directly compressible agglomerates was prepared by crystallo-co-agglomeration (CCA) technique and evaluated. Design of experimental (DoE) was carried out to evaluate the interactions and effects of the design factors on critical quality attributes (CQAs) of agglomerates. The design space was studied by DoE and multivariate analysis to ensure desired physico-chemical properties of agglomerates. The overall higher yield of the process with sufficient size of agglomerates was prepared by CCA. The optimized agglomerates exhibited excellent flowability and crushing strength along with good compressibility and compactibility. The optimized batch of agglomerates was characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry and gas chromatography which illustrated the absence of drug–excipient interaction with minimal entrapment of solvent. It was demonstrated that QbD principles and tools provide an effective means to achieve a greater understanding of agglomerates prepared by CCA which adopted as an excellent alternative to wet granulation.

Preparation and evaluation of agglomerated crystals by crystallo-co-agglomeration: An integrated approach of principal component analysis and Box–Behnken experimental design

Poor mechanical properties of crystalline drug particles require wet granulation technique for tablet production which is uneconomical, laborious, and tedious. The present investigation was aimed to improve flow and mechanical properties of racecadotril (RCD), a poorly water soluble antidiarrheal agent, by a crystallo-co-agglomeration (CCA) technique. The influence of various excipients and processing conditions on formation of directly compressible agglomerates of RCD was evaluated. Principal component analysis and Box-Behnken experimental design was implemented to optimize the agglomerates with good micromeritics and mechanical properties. The overall yield of the process was 88-98% with size of agglomerates between 351 and 1214 μm. Further, higher rotational speed reduced the size of agglomerates and disturbed sphericity. The optimized batch of agglomerates exhibited excellent flowability and crushing strength. The optimized batch of RCD agglomerates was characterized by fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry and gas chromatography which illustrated absence of drug-excipient interaction with minimal entrapment of residual solvent. Hence, it may be concluded that both excipients and processing conditions played a vital role to prepare spherical crystal agglomerates of RCD by CCA and it can be adopted as an excellent alternative to wet granulation.

Evidence does not support racecadotril use, says DTB

Evidence does not support racecadotril use, says DTB

Effects of racecadotril granules on infantile diarrhea

Objective To observe the clinical effects of racecadotril granules on infantile diarrhea.Methods 84 infants with acute diarrhea were divided randomly into two groups:the experimental group and the control group.The experimental group took both racecadotril granules and montorilonite powders,and the control group only took montorilonite powders.The character of stool,the days to recover normal stool,the total output of stool and the time of diarrhea between the two groups were observed.Results The total effective rate,the effective rate in the experimental group and that in the control group were 84.52%,97.6% and 71.42% respectively.There was a great difference between two groups via chi-square test(χ2 = 11.012,P =0.001 ).The experimental group had a higher effective rate than the control group.Conclusion Racecadotril granules and montorilonite powders have a better effect on infantile diarrhea than montorilonite powders only and was deserved to generalization. Key words: Diarrhea; Racecadotril granule; Montorilonite powder; Infant

Clinical observation of racecadotril granules in treating rotaviral enteritis in infants

Objective To investigate the curative effect of racecadotril granules on acute rotaviral enteritis in infants. Methods 100 infants with acute rotaviral enteritis were divided into combined treatment group(group A:50)cases and smecta group(B group:50 cases) ;Group B was given to basis of conventional therapy,but Group A received conventional therapy combined with clothing racecadotril particles. The efficacy and adverse reactions were observed.Results The time of improvement of vomiting,fever and diarrhea in A group was significantly shorter than the B group(t =2. 245,2. 298,2. 301, all P ＜ 0.05); The total effective rate 92. 0% in A group were higher than the B group 74. 0% after treatment 3d(x~2 = 3.987, P ＜ 0.05). The average course of treatment in A group (5.5 ± 0. 9) d was lower than the B group(7. 0 ± 1.1)d(t =7.17,P＜0.01). Conclusion Racecadotril is an effective and safe drug in treating rotaviral enteritis in infants. Key words: Rotavirus infections; Racecadotril graules; Child

Racecadotril: A novel antidiarrheal

Racecadotril: A novel antidiarrheal

Observation on the therapeutic effect on infants rotaviral enteritis treated with racecadotril combined with anisodamine

目的 观察消旋卡多曲联合山茛菪碱治疗婴幼儿轮状病毒性肠炎的疗效.方法 将124例符合条件的轮状病毒性肠炎的患儿随机分为两组,每组62例.常规治疗为抗病毒,补液(口服ORS或输液)纠正脱水,酸中毒,对症支持治疗.在此基础上,观察组加服消旋卡多曲+山茛菪碱;对照组加服八面蒙脱石散+双歧杆菌三联乳菌散.观察两组疗效.结果 观察组与对照组的总有效率分别为95%和79%,两组总有效率差异有统计学意义(P<0.05),观察组明显优于对照组.两组不良反应发生率分别为5%和2%.结论 消旋卡多曲联合山莨菪碱治疗婴幼儿轮状病毒性肠炎疗效显著、安全。

Racecadotril

Racecadotril

Racecadotril Effective for Pediatric Diarrhea

Oral rehydration is the primary treatment for acute watery diarrhea in children. Opiate drugs such as loperamide, used as adjunctive therapy, disrupt

Racecadotril

Racecadotril

Racecadotril

Racecadotril