Itopride Hydrochloride Research Articles

Formulation and in vitro evaluation of a thermoreversible mucoadhesive nasal gel of itopride hydrochloride

Itopride hydrochloride (ITO HCl) is a prokinetic agent, used in the treatment of gastrointestinal motility disorders. The aim of the study was to develop stable mucoadhesive thermoreversible nasal gel to avoid first pass effect. ITO HCl was incorporated into the blends of thermoreversible polymers like poloxamer 407 and various mucoadhesive polymers in different concentrations to increase the contact of the formulations with nasal mucosa. The compatibility between the drug and the suggested polymers was studied by Fourier transform infrared and differential scanning calorimetry (DSC). The formulations were evaluated for clarity, pH, gelation temperature, mucoadhesive strength, gel strength, viscosity, and drug content. In addition, the in vitro drug release and the dissolution efficiency (DE)% were measured. The optimized formulations that showed the highest dissolution efficiency% (DE%) in saline phosphate buffer of pH 6.4 at 35 ± 0.5 °C were chosen for stability testing at temperatures of 4 ± 2 and 25 ± 2 °C/60 ± 5% RH. It was found that F1 and F17 that contain 18% w/v poloxamer 407 and 0.5% w/v of hydroxypropylmethyl cellulose K4M or methyl cellulose (MC), respectively, showed higher stability results as indicated by their higher t90 values (days).

β-cyclodextrin-enhanced Spectrofluorometric Methods for the Determination of Substituted Benzamides (Itopride Hydrochloride, Alizapride, and Mosapride Citrate) in Pharmaceutical Preparations

Two spectrofluorometric methods are developed and optimized for the determination of substituted benz amides, namely itopride hydrochloride (ITO), alizapride (ALI), and mosapride citrate (MOS), in drug substances and pharmaceutical formulations. The first method is based on the measurement of the relative fluorescence intensity of the cited drugs in the absence of methyl-β-cyclodextrin at 380 ± 2 nm using an excitation wavelength of 310 nm in an aqueous solution. The linearity ranges were found to be 0.05–10, 0.1–10, and 0.1–10 μg/mL, with mean recoveries of 100.04% ± 0.21, 100.06% ± 0.65, and 100.08% ± 0.26 for ITO, ALI, and MOS, respectively. The second method is based on the significant enhancement of the fluorescence intensities of the drugs produced through complex formation with methyl-β-cyclodextrin in an aqueous solution at pH 6.6 in the case of ITO and pH 7.2 in the case of ALI and MOS. The fluorescence intensities of the formed complexes were measured at 420 ± 2 nm using an excitation wavelength of 310 nm. The linearity ranges were found to be 5–35, 3–15, and 2–30 ng/mL, with mean recoveries of 100.22 ± 30, 100.12 ± 0.24, and 100.30 ± 0.44, and limits of detection of 1.98, 1.32, and 0.66 ng/mL for ITO, ALI, and MOS, respectively. 1:1 stoichiometries for β -CD-drugs complexes were established. Association constants and Gibbs free energy were calculated by applying the Benesi–Hil de brand equation. The results were found to agree statistically with those obtained from the reference methods.

Особливості лікування гастроезофагеальної рефлюксної хвороби у хворих на цукровий діабету ІІ типу

In the world scientific literature sources, the issue of the combined course of gastroesophageal reflux disease (GERD) and diabetes mellitus (DM) is actively discussed. Along with this, research is necessary to select effective therapeutic complexes that have a multidirectional positive effect in patients with comorbid pathology, especially in type 2 DM and GERD. The purpose of the study is to investigate the effectiveness of complex therapy (ursodeoxycholic acid and itopride hydrochloride) in patients with combination of GERD and type 2 DM.Materials and methods. 54 patients with combination of type 2 DM and GERD were examined. The treatment of the patients with type 2 DM was conducted in accordance with the clinical treatment protocol of the Ministry of Health of Ukraine and local protocols. The standard anti-helicobacter therapy has been carried out for 14 days in HP-positive patients with combination of GERD and type 2 DM. Ulsepan treatment was prolonged to 1 month, if necessary than longer. The itopride hydrochloride was prescribed in dose 50 mg 3 times a day for 1 month to normalize the functioning of upper gastrointestinal tract section. All patients with combination of type 2 DM and GERD have been prescribed ursodeoxycholic acid (UDCA) in dose 15 mg / kg body weight. UDCA treatment lasted for up to 6 months.Results. The study included patients with type 2 DM medium severity. The leading clinical manifestation of the upper digestive tract section in patients with type 2 DM was bloating of acid, heartburn and globus pharyngeus. The prescribed antisecretory therapy (if necessary, anti-helicobacter treatment) in combination with itopride hydrochloride and UDCA in patients with type 2 DM positively influenced on the clinical and endoscopic manifestation of GERD in patients with type 2 DM. Complex therapy with the use of UDCA resulted in a significant reduction in the number of patients with duodeno - gastral reflux (DER), namely from 48.1% to 3.7%, respectively (p <0.01). The expressed positive effect on the dynamics of the body mass index in patients with combination of type 2 DM and GERD was observed on the background of co mplex therapy with the use of UDCA.Conclusion. The use of itopride hydrochloride (Ganaton) in combination with pantoprazole (Ulsepan) is an effective method for correction of the esophageal and extra-esophageal clinical manifestations of GERD in patients with type 2 DM. UDCA (Holudexan) is a safe and effective way to reduce the severity of DGR in GERD, and also helps to reduce body weight in patients with type 2 DM with a violation of body mass index in course of its application.

An Efficient and Improved Process for the Synthesis of Itopride Hydrochloride and Trimethobenzamide Hydrochloride

Aim and Objective: Itopride is a prokinetic agent used for treating conditions like non-ulcer dyspepsia. Itopride is administered as its hydrochloride salt. Trimethobenzamide is used for treating nausea and vomiting and administered as its hydrochloride salt. The aim is to develop a novel and environmental friendly method for large-scale production of itopride and trimethobenzamide. Materials and Methods: Itopride and trimethobenzamide can be prepared from a common intermediate 4- (dimethylaminoethoxy) benzyl amine. The intermediate is prepared from one pot synthesis using Phyrdroxybenzaldehye and zinc dust and further reaction of the intermediate with substituted methoxy benzoic acid along with boric acid and PEG gives itopride and trimethobenzamide. Results: The intermediate 4-(dimethylaminoethoxy) benzylamine is prepared by treating p-hydroxybenzaldehyde and 2-dimethylaminoethyl chloride. The aldehyde formed is treated with hydroxylamine hydrochloride. The intermediate is confirmed by NMR and the purity is analysed by HPLC. Conclusion: Both itopride and trimethobenzamide were successfully synthesized by this method. The developed method is environmental friendly, economical for large-scale production with good yield and purity.

Современные возможности применения прокинетиков в лечении больных с гастроэзофагеальной рефлюксной болезнью

Aim of the lecture. To present modern approaches to prokinetic treatment at gastroesophageal reflux disease (GERD) to gastroenterologists. Summary. GERD belongs to acid-related diseases, because detrimental action of hydrochloric acid on esophageal mucosa plays major role in its pathogenesis. However esophageal and stomach motility disorders, e.g.: increase in frequency of transient lower esophageal sphincter relaxations, decrease of esophageal clearance and increase of intragastric pressure play important role in GERD development as well. These factors along with the not uncommon resistance of GERD patients to the proton pump inhibitors (PPI) caused by nonacidic refluxes require prokinetic administration. Most commonly prokinetics are prescribed as supplemental to PPI treatment. At the present time the optimal prokinetic drug, with proved efficacy at GERD and other diseases associated to gastrointestinal dysmotility is itopride hydrochloride (Ganaton®). Conclusion. Taken into account important role of esophageal and stomach dysmotility in GERD pathogenesis, prokinetics can be recommended for comprehensive disease treatment, especially at PPI inefficacy.

Quantification of Itopride Hydrochloride from tablet dosage form by visible Spectroscopy

The present study to describe the Quantification of Itopride Hydrochloride from tablet dosage form by visible spectroscopy by applying principle of colorimetric study. It involves the measurement of the amount of ultraviolet (190-380 nm) or visible (380-800nm) radiation absorbed by a substance in solution. The final optimised method carried out on double beam UV-visible spectrophotometer (Shimadzu, model 1800) having two matched quartz cells with 1 cm light path by using Bromothymol blue of concentration 0.5% w/v solution. Itopride Hydrochloride detection wavelength was set at 479.40nm The linearity was found to be in the range of 10-50µg/ml. This method for the quantitative determination of the drug by validation in accordance with the International Conference on Harmonization. The proposed method is economic, simple, sensitive, reproducible, and accurate and no interference is observed due to common excipients of tablet. The proposed method was successfully applied to determination of Itopride hydrochloride in pharmaceutical formulations.

A randomised double blind trial to compare the efficacy and tolerability of itopride hydrochloride versus domperidone in patients with non-ulcer dyspepsia: bloating predominant type

Background: Non-ulcer dyspepsia is a treatment challenge due to multiple pathophysiological mechanisms and different symptoms. Several prokinetic drugs are tried without any unanimity regarding safety and efficacy. The objective of the study was to compare the efficacy and safety of Itopride and Domperidone in bloating predominant non ulcer dyspepsia patients.Methods: Patients were randomly assigned to two groups (20 each) to receive either 50mg of Itopride three times daily or 10mg of Domperidone three times daily. Only patients with predominant bloating were considered and their baseline symptoms recorded. The symptoms were graded on a 4-point scale - the Global Symptom Score scale and the patients were reassessed at the end of 2 and 4 weeks. The relief of symptoms was also assessed at the end of 2 and 4 weeks on a 5-point scale - The Patients’ Subjective Global Assessment of Relief scale.Results: Both the drugs significantly produced symptomatic relief. Though Domperidone is marginally beneficial compared to Itopride after 4 weeks treatment in terms of improvement in symptom scores, the Subjective Global Assessment of relief did not show any significant improvement between the two drugs.Conclusions: Treatment with Itopride was safe, well tolerated, resulted in good symptomatic relief, and was comparable in efficacy to Domperidone in relieving the symptoms of NUD. Hence it can be considered a good alternative for the treatment of non-ulcer dyspepsia.

Differentiation therapy for non-acidic gastroesophageal reflux disease

To investigate the clinical and pathogenetic features of the non-acidic types of gastroesophageal reflux disease (GERD) and to evaluate the impact of combined therapy versus monotherapy on the course of this disease. The investigation enrolled 62 patients with non-acidic GERD. The follow-up period was 6 weeks. The patients were divided into 2 groups: 1) weakly acidic gastroesophageal refluxes (GER); 2) weakly alkaline GER. Then each group was distributed, thus making up 4 groups: 1) 19 patients with weakly acidic GER who received monotherapy with rabeprazole 20 mg/day; 2) 21 patients with weakly acidic GER had combined therapy with rabeprazole 20 mg and itopride; 3) 8 patients with weakly alkaline GER who received ursodeoxycholic acid (UDCA) monotherapy; and 4) 14 patients with weakly alkaline GER who had combined therapy with UDCA and itopride, The clinical symptoms of the disease, the endoscopic pattern of the upper gastrointestinal tract (GIT) mucosa, histological changes in the esophageal and gastric mucosa, and the results of 24-hour impedance pH monitoring were assessed over time. During differentiation therapy, the majority of patients reported positive clinical changes and an improved or unchanged endoscopic pattern. Assessment of impedance pH monitoring results revealed decreases in the overall number of GERs, the presence of a bolus in the esophagus, and the number of proximal refluxes. These changes were noted not only in patients taking proton pump inhibitors (PPIs), but also in those treated with UDCA monotherapy or combined PPI and prokinetic therapy. A differentiated approach to non-acidic GER treatment contributes to its efficiency. Adding the prokinetic itomed (itopride hydrochloride) to PPI therapy in a patient with weakly acidic GER enhances the efficiency of treatment, by positively affecting upper GIT motility. The mainstay of therapy for GERD with a predominance of weakly alkaline refluxes is UDCA, the combination of the latter and the prokinetic can exert a more pronounced effect on the clinical and endoscopic pattern and upper GIT motility.

Применение итоприда гидрохлорида (ганатон) в лечении дуоденогастрального рефлюкса (ДГР) у больных с функциональной диспепсией и синдромом раздраженного кишечника с запорами

Применение итоприда гидрохлорида (ганатон) в лечении дуоденогастрального рефлюкса (ДГР) у больных с функциональной диспепсией и синдромом раздраженного кишечника с запорами

FUNCTIONAL GASTROINTESTINAL DISORDERS: SELECT FROM THE POINT PROKINETIC COMORBIDITY, CLINICAL EFFICACY AND DRUG SAFETY

Functional gastrointestinal disorders are currently being considered as the most common pathology of the gastrointestinal tract. Symptoms that may be related to the gastroduodenal region, represent one of the major subgroups among functional gastrointestinal disorders, in which the functional dyspepsia rightly maintains leading positions syndrome. Pathogenetic factors of functional dyspepsia and other functional gastrointestinal disorders, which can be regarded as proven at the moment, are the dysmotility of the gastrointestinal tract, which determines the feasibility of using in the basic treatment of these diseases medications that affect motor function of the gastrointestinal tract and preventing anastaltic contractions of the smooth muscles, which are combined into a group of prokinetic. With comorbidity positions, clinical efficacy and drug safety is a priority itopride hydrochloride prokinetics in treatment of functional dyspepsia and other related functional gastrointestinal disorders.

USE OF ION ASSOCIATION COMPLEX FORMATION FOR THE SPECTROPHOTOMETRIC DETERMINATION OF ITOPRIDE HCL IN BULK AND ITS PHARMACEUTICAL PREPARATIONS

Objective: The authors report two simple, accurate and economic spectrophotometric methods A and B for the determination of Itopride hydrochloride in bulk and dosage forms.Methods: The proposed methods are based on the formation of chloroform soluble ion-associates in the presence of acidic dyes namely BPB (Method A) and BCP (Method B) exhibiting lmax at 418 and 418 nm respectively.Results: Beer’s law is found to be obeyed in the concentration range of 2.0-10.0 µg/ml and 2.0-10.0 µg/ml. The molar absorptivities are found to be 1.42x104 and 9.61x103L/mol. cm for methods A and B. These methods are successfully applied for the assay of Itopride hydrochloride in pharmaceutical formulations.

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

PurposeThe aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form.Materials and methodsSustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release.ResultsIn vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031). The pharmacokinetic results indicated that the area under the curve (AUC0–∞) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton®) and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022).ConclusionThe prepared floating tablets of ITO HCl (F10) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

Molecularly imprinted polymer-based bulk optode for the determination of itopride hydrochloride in physiological fluids

We report here for the first time on the use of Molecularly Imprinted Polymers as modifiers in bulk optodes, Miptode, for the determination of a pharmaceutical compound, itopride hydrochloride as an example in a concentration range of 1×10−1–1×10−4molL−1. In comparison to the optode containing the ion exchanger only (Miptode 3), the optode containing the ion exchanger and the MIP particles (Miptode 2) showed improved selectivity over the most lipophilic species, Na+ and K+, by more than two orders of magnitude. For instance, the optical selectivity coefficients using Miptode 2, logKIP,J+=opt, were as follow: NH4+˂−6; Na+=−4.0, which were greatly enhanced in comparison with that obtained by Miptode 3. This work opens a new avenue for using miptodes for the determination of all the pharmaceutical preparations without the need for the development of new ionophores.

Effect of Trimebutine maleate on reflux esophagitis in elderly patients

Objective To investigate the effect of Trimebutine maleate on reflux esophagitis in elderly patients. Methods A total of 160 elderly patients with typical esophageal reflux symptoms diagnosed as reflux esophagitis by gastroscope, with concomitant gastroesophageal disease confirmed by esophageal motility manometry and 24 h esophageal pH impedance monitoring acid reflux, were selected and retrospectively analyzed. All patients were treated with proton pump inhibitor(PPI)esomeprazole 20 mg tid, antecibum(AC)for 8 weeks, and randomly divided into four groups: group A(itopride hydrochloride 50 mg tid, AC), group B(citrate mosapride 5 mg tid, AC), group C(trimebutine maleate 200 mg tid, AC), group D(treated without prokinetic drugs). After 4 and 8 weeks of therapy, the symptom improvements were observed in the four groups. Endoscopy, esophageal motility manometry, 24h esophageal pH impedance monitoring were performed in the 160 cases after 8 weeks of treatment. Results The total effective rate was 97.5%(39 cases), 95.0%(38 cases), 92.5%(37 cases)and 77.5%(31 cases)in group A, B, C and D respectively after 8 weeks of treatment. Endoscopic examination showed that the cure rate was 70.0%(28 cases), 62.5%(25 cases), 72.5%(29 cases), 67.5%(27 cases), and the effective rate was 87.5%, (35 cases), 92.5%(37 cases), 87.5%(35 cases)and 87.5%(35 cases)in group A, B, C and D respectively after 8 weeks of treatment, without statistically significant differences in the cure rate and effective rate between the four groups. The results of esophageal motility manometry showed that the lower esophageal sphincter pressure(LESP), lower esophageal sphincter relaxation(LESR), lower esophageal peristaltic wave pressure(LEPP)and percentage of abnormal esophageal body contraction had significant difference before versus after treatment in group A and B, but not in control group. The improvements in the percentage of total time of pH 5 min, the longest reflux time(min)at supine position were more significant in group A, B and C than in group D. Compared with pre-treatment, the times of non-acid reflux were reduced significantly in group A, B and D(all P<0.01), and there was a significant difference(P<0.05)between the three(A, B, C)groups and group D(P<0.05). There were significant differences in the times of reflux liquid and gas reflux between the group A, B and D(P<0.05). The proximal reflux times were improved more significantly in group A, B and C after treatment than in control group(P<0.05). Conclusions Prokinetic drugs combined with PPI therapy has better effect than single PPI application in improving the clinical symptoms and upper gastrointestinal motility in elderly patients with RE. Trimebutine maleate is safe and effective in the elderly, and has a similar effect on esophageal motility with mosapride citrate and itopride hydrochloride, which may be involved in selectively improving esophageal motility, lower esophageal sphincter pressure and gastric emptying function. Key words: Esophagitis, peptic; Trimebutine maleate; Proton pump inhibitors

GASTROESOPHAGEAL REFLUX DISEASE IN PATIENTS WITH FUNCTIONAL DYSPEPSIA AND CONSTIPATION PREDOMINANT IRRITABLE BOWEL SYNDROME: CLINICAL FEATURES AND EFFICACY OF LACTULOSE AND ITOPRIDE HYDROCHLORIDE

Актуальность. В ряде исследований описано частое сочетание гастроэзофагеальной рефлюксной болезни (ГЭРБ), функциональной диспепсии (ФД) и синдрома раздраженного кишечника (СРК). Цель – изучить особенности клинического течения и диагностики ГЭРБ в сочетании с ФД и СРК с запором (СРК-З) по сравнению с изолированным течением ГЭРБ, а также оценить эффективность терапии лактулозой и итоприда гидрохлоридом. Материал и методы. Обследовано 60 пациентов, страдающих ГЭРБ в сочетании с ФД (Римские критерии III) и СРК-З (Римские критерии III) и 29 больных только с ГЭРБ. Диагноз ГЭРБ устанавливали на основании клинических, эндоскопических и рН-метрических критериев. На протяжении 4 недель 10 больных с сочетанием неэрозивной рефлюксной болезни (НЭРБ), ФД и СРК-З принимали лактулозу, 10 больных – комбинацию лактулозы с итоприда гидрохлоридом. Клиническую симптоматику и показатели рН-метрии оценивали до и через 4 недели после терапии.Результаты. Сочетание ГЭРБ, ФД и СРК-З чаще встречалось у женщин моложе 40 лет с нормальным индексом массы тела (р<0,05). Классических симптомов ГЭРБ не отмечалось у 43,4% больных с коморбидной патологией желудочно-кишечного тракта и у 10,3% – с изолированным течением ГЭРБ (р=0,004). Распространенность жалоб на отрыжку воздухом и тошноту была выше среди пациентов с сочетанием ГЭРБ, ФД и СРК-З, чем среди больных с изолированным течением ГЭРБ (р<0,05). Через 4 недели лечения у пациентов с сочетанием НЭРБ, ФД и СРК-З, получавших лактулозу в комбинации с итоприда гидрохлоридом, наблюдались уменьшение выраженности клинической симптоматики (p<0,05) и нормализация рН-метрических показателей (р<0,001). Заключение. Течение ГЭРБ у больных с ФД и СРК-З сопряжено со следующими особенностями: преобладанием лиц женского пола, отсутствием классических симптомов ГЭРБ почти у половины больных, частым присоединением других функциональных симптомов. Применение комбинации лактулозы и итоприда гидрохлорида позволяет успешно контролировать клинические симптомы ГЭРБ и ФД, а также уровень рН в пищеводе.

Itopride hydrochloride combined with Bifidobacterium triple viable capsules for treatment of abdominal distention in chronic hepatitis B patients with liver cirrhosis

Itopride hydrochloride combined with <i>Bifidobacterium</i> triple viable capsules for treatment of abdominal distention in chronic hepatitis B patients with liver cirrhosis

Efficacy of itopride combined with alpha-lipoic acid for patients with diabetic gastroparesis

Objective To evaluate the efficacy of itopride hydrochloride combined with alpha-lipoic acid in treatment of diabetic gastroparesis. Methods One hundred and ten patients with diabetic gastroparesis were randomly assigned to two groups. Sixty patients received α-lipoic acid plus itopride (α-lipoic acid 0.6 g intravenously for 14 d plus itopride 50 mg orally t. i.d), and 50 cases received oral itopride only.The clinical symptoms including postprandial abdominal fullness, belching, acid reflux, anorexia, nausea and vomiting were observed; the gastric emptying rate was tested, and plasma motilin and serum ganstrin levels were measured groups, before and after two weeks of treatment. Results The clinical symptom scores of combination therapy group (4.62±3.46 vs. 12.26±3.43) and control groups (5.43±3.65 vs. 12.31±3.37) were improved after treatment. The overall effective rate of combination group was 91.6% and that of itopride therapy group was 78.0% (χ2=4.098, P<0.05). Gastric emptying rate of combination group [(76.9±9.7)% vs. (37.3±10.2) %] was increased more markedly than that of itopride group[(57.2±10.4)% vs. (36.8±11.2)%] (t=10.221, P<0.05). Plasma motilin and serum ganstrin levels in combination group [(640.2±64.4)ng/L vs. (554.0±67.6)ng/L, (152.6±20.3)ng/L vs. (96.8±22.2)ng/L] were reduced more markedly than those in itopride group [(636.3±66.4)ng/L vs. (589.4±48.3)ng/L, (153.5±19.4)ng/L vs. (120.9±19.7)ng/L] respectively (t=3.100, 5.959, all P<0.05). Conclusion For patients with diabetic gastroparesis, α-lipoic acid and itopride combination therapy can significantly improve symptoms and gastric emptying rate, decrease motlin and gastrin levels; and the efficacy of combination therapy is better than that of itopride monotherapy. Key words: Diabetes mellitus; Gastroparesis; Tiapride; Thioctic acid

Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia.

Background/AimsTherapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients.MethodsPatients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspeptic symptoms and the overall treatment effect. Impact on patients’ quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire.ResultsWe randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as ≥ 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable.ConclusionsDA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with comparable safety.

Novel potentiometric application for the determination of pantoprazole sodium and itopride hydrochloride in their pure and combined dosage form

Three sensitive and selective polyvinyl chloride (PVC) matrix membrane electrodes were developed and investigated. Sensor I was developed using tetraheptylammonium bromide (THB) as an anion exchanger with 2-nitrophenyl octyl ether (2-NPOE) as a plasticizer for the determination of the anionic drug pantoprazole sodium sesquihydrate (PAN). To determine the cationic drug itopride hydrochloride (ITH), two electrodes (sensors II and III) were developed using potassium tetrakis(4-chlorophenyl) borate (KTCPB) as a cation exchanger with dioctyl phthalate (DOP) as a plasticizer. Selective molecular recognition components, 2-hydroxypropyl-β-cyclodextrin (2-HP βCD) and 4-tert-butylcalix[8]arene (tBC8), were used as ionophores to improve the selectivity of sensors II and III, respectively. The proposed sensors had a linear dynamic range of 1×10−5 to 1×10−2molL−1 with Nernstian slopes of −54.83±0.451, 56.90±0.300, and 51.03±1.909mV/decade for sensors I, II and III, respectively. The Nernstian slopes were also estimated over the pH ranges of 11–13, 3.5–8 and 4–7 for the three sensors, respectively. The proposed sensors displayed useful analytical characteristics for the determination of PAN and ITH in bulk powder, in laboratory prepared mixtures and in combined dosage forms with clear discrimination from several ions, sugars and some common drug excipients. The method was validated according to ICH guidelines. Statistical comparison between the results from the proposed method and the results from the reference methods showed no significant difference regarding accuracy and precision.

Controlled Release Ion Sensitive Floating Oral in situ Gel of a Prokinetic Drug using Gellan Gum.

Abstract: There are various approaches commonly used for gastric retention, one of which is raft forming system. Floating oral in situ gel is a type of raft forming system. The present work concerns with the formulation, evaluation and optimization of floating oral in situ gel of Itopride Hydrochloride for controlled release. Gellan gum has been used as a gel forming polymer and calcium carbonate as cross linking agent and Ca2+ ion source, and HPMC K100M as release retardant. The floating oral in situ gel undergoes gelation by ion sensitive mechanism. In this formulation 32 factorial designs was performed and the effect of variation in concentration of gellan gum and HPMC K100M on drug release at 1 h, 6 h, and viscosity was evaluated. The gel was evaluated for other parameters like floating lag time, floating duration, gel strength, density, pH, in vitro drug release, drug content, and in vitro gelling capacity. The results of 32 full factorial design revealed that the concentration of gellan gum and of HPMC K100M significantly affected the dependent variables i.e. drug release at 1 h, at 6 h, and viscosity. A controlled release profile was observed for these formulations. The drug release mechanism was found to follow Korsmeyer-Peppas model. In vivo studies revealed higher Tmax of gel compared to plain drug which is suggestive of slower absorption. However the AUC0-12 h was found to be nearly 90% higher than plain drug. Key words: in situ gel, CaCO3, Gellan gum, Foating drug delivery system, Ion Sensitive, Prokinetic.