AIM:To investigate the incidence of nocturnal dyspeptic symptoms in patients with functional dyspepsia(FD) and whether prokinetic drugs can alleviate them. METHODS:Eighty-five consecutive Chinese patients with FD were...AIM:To investigate the incidence of nocturnal dyspeptic symptoms in patients with functional dyspepsia(FD) and whether prokinetic drugs can alleviate them. METHODS:Eighty-five consecutive Chinese patients with FD were included in this study.One week after single-blinded placebo run-in treatment,baseline nocturnal intragastric pH,bile reflux and nocturnal dyspeptic symptoms of eligible patients,including epigastric pain or discomfort,abdominal distention and belching, were investigated with questionnaires.Patients exhibiting nocturnal dyspeptic symptoms were randomly and double-blindly assigned to domperidone group or placebo group.Nocturnal intragastric pH and percentage of duodenogastric bile reflux time were determined after treatment. RESULTS:Of the 85 FD patients,2 females withoutnocturnal symptoms,who responded to placebo run-in treatment,were excluded from the study,30(36.1%) exhibited nocturnal dyspeptic symptoms with increased duodenogastric bile reflux time(intragastric bilirubin absorbance>0.14)and mean gastric pH(confirming the existence of bile reflux)(P=0.021,0.023) at night were included in the study.Of these 30 patients,21(70%)had overt nocturnal duodenogastric bile reflux,which was significantly higher than that of those without nocturnal symptoms(P=0.026).The 30 patients were allocated to domperidone group or placebo group(n=15).The nocturnal duodenogastric bile reflux and gastric pH were significantly decreased after domperidone treatment(P=0.015,0.021).The severity score of nocturnal dyspeptic symptoms was also significantly decreased after domperidone treatment (P=0.010,0.015,0.026),which was positively correlated with the reduced nocturnal bile reflux or gastric pH(r=0.736,0.784,0.753 or r=0.679,0.715,0.697, P=0.039,0.036,0.037 or P=0.043,0.039,0.040). CONCLUSION:A subgroup of Chinese FD patients show overt nocturnal dyspeptic symptoms,which may be correlated with the excessive nocturnal duodenogastric bile reflux.Domperidone therapy can alleviate these symptoms.展开更多
A simple and sensitive fluorescence detection of domperidone by ultra fast liquid chromatographic method was developed and validated in human serum. For the evaluation of new drug delivery systems, conducting of pharm...A simple and sensitive fluorescence detection of domperidone by ultra fast liquid chromatographic method was developed and validated in human serum. For the evaluation of new drug delivery systems, conducting of pharmacokinetic studies in human volunteers is essential for approval to marketing after preclinical evaluation in animal models. The present method consists of protein precipitation, extraction of analytes from human serum into dichloromethane and separation using reversed-phase C<sub>18</sub> column. Propranolol hydrochloride was used as an internal standard and the eluent was monitored by fluorescence detector at excitation 282 and emission 328 nm. The mobile phase used was 62:38 ratio of 10 mM phosphate buffer pH adjusted to 3.1 with OPA and methanol at a flow rate of 1 mL·min<sup>-1</sup>. The method was evaluated for assay, LLOD, LLOQ, recovery and stability studies. The retention times for domperidone and propranolol hydrochloride were found to be 6.36 and 7.94 minutes respectively. The intraday and inter-day coefficient of variation and percent error values of assay method were less than 5%;mean recovery was more than 96% for each analyte and the method was found to be precise, accurate and specific during study. The method was successfully applied for pharmacokinetic study of immediate and controlled release bioadhesive hot melt extruded buccal patches of domperidone after buccal administration to healthy human volunteers. The C<sub>max</sub>, T<sub>max</sub>, and AUC<sub>0–24 </sub>of domperidone from immediate and controlled release buccal patches were found to be 129.7 ng·mL<sup>-1</sup>, 1.5 h, 455.1 ng·h·mL<sup>-1</sup> and 145.7 ng·mL<sup>-1</sup>, 5.25 h, 911.0 ng·h·mL<sup>-1</sup> respectively. A simple, sensitive and reliable method for the fluorescence determination of domperidone in human serum by UFLC method was developed and validated.展开更多
A rapid, sensitive, and accurate method based on LC/MS/MS was developed and validated for the determination of domperidone in human plasma. Domperidone and internal standard, tramadol, were extracted from plasma with ...A rapid, sensitive, and accurate method based on LC/MS/MS was developed and validated for the determination of domperidone in human plasma. Domperidone and internal standard, tramadol, were extracted from plasma with di- ethyl ether-dichloromethane （60： 40, volume ratio） and separated by reversed-phase HPLC with methanol-water-am- monia solution（80： 20： 0.2, volume ratio） as the mobile phase. Detection was carried out v/a multiple-reaction moni-toting（MRM） on a Q-trap^TM LC/MS/MS system（Q-trap^TM）. The assay result was linear over a concentration range of 0.1-30 ng/mL with a limit of quantitation （LOQ） of 0.1 ng/mL. The inter-and inn＇a-day precision levels were within 7.52% and 12.9%, respectively, whereas the accuracy was within a range of 87.3%-114%. This method has been successfully applied to evaluate the pharmcokinetics of domperidone in Chinese healthy volunteers given an oral dose of 10 mg.展开更多
Abstract： Commercially available domperidone -a D2 receptor antagonist- is an immediate release formulation which has never been formulated into microspheres for sustained release. The present work aims towards study...Abstract： Commercially available domperidone -a D2 receptor antagonist- is an immediate release formulation which has never been formulated into microspheres for sustained release. The present work aims towards studying the effect of combination of a natural chitosan from an oyster shell of Mystilis edulis and HPMC （hydroxy propyl methyl cellulose） （spectracel 15 E） as polymer and tripolyphosphate as cross linking agent using wet gelation technique. The various polymer combination ratios for different batches were compared with a low molecular weight standard chitosan. The extracted chitosan - HPMC polymer combination ratios were chosen at ten levels： as batches B1, B2, B3, B4, B5, B6, B7, B8, B9, B10 for 1：1, 1：2, 2：1, 1：0, 0：1, 3：1, 1：3, 5：1, and 1：5 and 1：1 having 450：450, 300：600, 600：300, 900：0, 0：900, 675：225, 225：675, 750：150, 150：750, 450：450 mg respectively, while the quantity of domperidone and tripolyphosphate remained constant. B 11 and B 12 were formulated with standard chitosan and HPMC. The percentage yield of the formulated microspheres was determined and then evaluated for flowability, drug entrapment efficiency, drug release and mechanism of drug release by Fickian diffusion. The best batches of the domperidone loaded microspheres produced from the combination polymer were compared with the standard chitosan. The highest yields of microspheres were given by batches B12, B11, B10, and B4 with values of 50.1 ± 0.1%, 49.6 ± 0.1%, 46.6 ：± 0.1%, and 46.1 ± 0.0% respectively while the lowest yield were 23.3 ± 0.2% and 23.6 ± 0.2%. B5 and B6 and B9 did not yield any microsphere. The bulk density, tapped density, compressibility and Hausner＇s ratio of the microspheres showed good flowability and high percent compressibility. The drug entrapment efficiency showed that the entrapment ranged from 54.2 to 97.2, where the least entrapment was B4 （54.2 ± 0.1） and the highest B12 （97.2 ± 0.2）. The polymer surface of the microspheres as observed by SEM （scanning electron microscopy） was heterogeneous and porous which offers enhanced bioadhesivity. The dissolution study was used to determine the percentage drug release which ranged from 12.1% to 68.9% after 5 hours. Batches 1, 2, 3, 4, 7, and I 1 follow zero order kinetics via Fickian diffusion. The results indicate that microspberes of domperidone could be successfully formulated with a natural chitosan either alone or in combination with HPMC for sustained delivery of domperidone. Furthermore, the concentration of the natural polymer and HPMC employed in the formulation need to be carefully selected to enable the production of microspheres with the desired sustained release properties.展开更多
Gastroeophageal reflux is a condition in which the acidified liquid content of the stomach backs up into the esophagus. The antiacid magaldrate and prokinetic domperidone are two drugs clinically used for the treatmen...Gastroeophageal reflux is a condition in which the acidified liquid content of the stomach backs up into the esophagus. The antiacid magaldrate and prokinetic domperidone are two drugs clinically used for the treatment of gastroesophageal reflux symptoms. However, the evidence of a superior effectiveness of this combination in comparison with individual drugs is lacking. A double-blind, randomized and comparative clinical trial study was designed to characterize the efficacy and safety of a fixed dose combination of magaldrate (800 mg)/domperidone (10 mg) against domperidone alone (10 mg), in patients with gastroesophageal reflux symptoms. One hundred patients with gastroesophageal reflux diagnosed by Carlsson scale were randomized to receive a chewable tablet of a fixed dose of magaldrate/domperidone combination or domperidone alone four times each day during a month. Magaldrate/domperidone combination showed a superior efficacy to decrease global esophageal (pyrosis, regurgitation, dysphagia, hiccup, gastroparesis, sialorrhea, globus pharyngeus and nausea) and extraesophageal (chronic cough, hoarseness, asthmatiform syndrome, laryngitis, pharyngitis, halitosis and chest pain) reflux symptoms than domperidone alone. In addition, magaldrate/domperidone combination improved in a statistically manner the quality of life of patients with gastroesophageal reflux respect to monotherapy, and more patients perceived the combination as a better treatment. Both treatments were well tolerated. Data suggest that oral magaldrate/domperidone mixture could be a better option in the treatment of gastroesophageal reflux symptoms than only domperidone.展开更多
Domperidone Maleate (DOM), an antiemetic drug, has been used in treatment of adults and children. It has low aqueous solubility and hence low bioavailability. In present study, an attempt has been made to enhance the ...Domperidone Maleate (DOM), an antiemetic drug, has been used in treatment of adults and children. It has low aqueous solubility and hence low bioavailability. In present study, an attempt has been made to enhance the solubility of DOM by inclusion complexation with Hydroxypropyl-β-Cyclodextrin (HP-β-CD) using kneading technique and formulation of fast disintegrating tablets by using Sodium Starch Glycolate as superdisintegrant. Solubility analysis of DOM in different concentrations of HP-β-CD was carried out. Design of experiment (DOE) is done by using MINITAB 15.1 software to find out the variable for dissolution and disintegration time. HP-β-CD and SSG were identified as the variable for disintegration time and dissolution. For optimization of the concentration of HP-β-CD and SSG, two factors at two levels design through central composite design (CCD) were used which gave 13 formulations. All formulations are evaluated for characteristics such as weight variation, hardness, friability, disintegration time and dissolution of drug. Solubility of DOM increases linearly with increase in concentration of HP-β-CD. The optimum concentration of HP-β-CD is found to be in 1:2 molar ratios and SSG of 7%. The In-Vitro dissolution studies of optimized formulation and market sample were carried out in USP type II apparatus at different time intervals of 5, 10, 15 and 30 minutes at 50 rpm in 0.1 N HCl. The dissolution and disintegration time of optimized formulation is found better than market sample.展开更多
Silica aerogel (SA) was loaded with domperidone to demonstrate the potentiality of adsorption processes based on the usage of supercritical carbon dioxide to treat poorly water-soluble drugs, forming new kinds of drug...Silica aerogel (SA) was loaded with domperidone to demonstrate the potentiality of adsorption processes based on the usage of supercritical carbon dioxide to treat poorly water-soluble drugs, forming new kinds of drug delivery systems. The effects of pressure, temperature and solution concentration on loaded SA were studied. Adsorption isotherms were measured at 35℃ and 45℃ and fitted with Langmuir model. Release kinetics of the adsorbed drug were also evaluated by in vitro dissolution tests. Results showed that domperidone can be uniformly dispersed into the aerogel and that the release rate of domperidone from the composite, constituted by drug and silica aerogel, is much faster than that of the crystalline drug. The proposed adsorption method is suitable for the production of domperidone fast release tablets.展开更多
基金Supported by Project of the National Key Technology R&D Program during the 11th Five-Year Plan Period,No.2007BAI04B01Shanghai Leading Academic Discipline Project,No.Y0205
文摘AIM:To investigate the incidence of nocturnal dyspeptic symptoms in patients with functional dyspepsia(FD) and whether prokinetic drugs can alleviate them. METHODS:Eighty-five consecutive Chinese patients with FD were included in this study.One week after single-blinded placebo run-in treatment,baseline nocturnal intragastric pH,bile reflux and nocturnal dyspeptic symptoms of eligible patients,including epigastric pain or discomfort,abdominal distention and belching, were investigated with questionnaires.Patients exhibiting nocturnal dyspeptic symptoms were randomly and double-blindly assigned to domperidone group or placebo group.Nocturnal intragastric pH and percentage of duodenogastric bile reflux time were determined after treatment. RESULTS:Of the 85 FD patients,2 females withoutnocturnal symptoms,who responded to placebo run-in treatment,were excluded from the study,30(36.1%) exhibited nocturnal dyspeptic symptoms with increased duodenogastric bile reflux time(intragastric bilirubin absorbance>0.14)and mean gastric pH(confirming the existence of bile reflux)(P=0.021,0.023) at night were included in the study.Of these 30 patients,21(70%)had overt nocturnal duodenogastric bile reflux,which was significantly higher than that of those without nocturnal symptoms(P=0.026).The 30 patients were allocated to domperidone group or placebo group(n=15).The nocturnal duodenogastric bile reflux and gastric pH were significantly decreased after domperidone treatment(P=0.015,0.021).The severity score of nocturnal dyspeptic symptoms was also significantly decreased after domperidone treatment (P=0.010,0.015,0.026),which was positively correlated with the reduced nocturnal bile reflux or gastric pH(r=0.736,0.784,0.753 or r=0.679,0.715,0.697, P=0.039,0.036,0.037 or P=0.043,0.039,0.040). CONCLUSION:A subgroup of Chinese FD patients show overt nocturnal dyspeptic symptoms,which may be correlated with the excessive nocturnal duodenogastric bile reflux.Domperidone therapy can alleviate these symptoms.
文摘A simple and sensitive fluorescence detection of domperidone by ultra fast liquid chromatographic method was developed and validated in human serum. For the evaluation of new drug delivery systems, conducting of pharmacokinetic studies in human volunteers is essential for approval to marketing after preclinical evaluation in animal models. The present method consists of protein precipitation, extraction of analytes from human serum into dichloromethane and separation using reversed-phase C<sub>18</sub> column. Propranolol hydrochloride was used as an internal standard and the eluent was monitored by fluorescence detector at excitation 282 and emission 328 nm. The mobile phase used was 62:38 ratio of 10 mM phosphate buffer pH adjusted to 3.1 with OPA and methanol at a flow rate of 1 mL·min<sup>-1</sup>. The method was evaluated for assay, LLOD, LLOQ, recovery and stability studies. The retention times for domperidone and propranolol hydrochloride were found to be 6.36 and 7.94 minutes respectively. The intraday and inter-day coefficient of variation and percent error values of assay method were less than 5%;mean recovery was more than 96% for each analyte and the method was found to be precise, accurate and specific during study. The method was successfully applied for pharmacokinetic study of immediate and controlled release bioadhesive hot melt extruded buccal patches of domperidone after buccal administration to healthy human volunteers. The C<sub>max</sub>, T<sub>max</sub>, and AUC<sub>0–24 </sub>of domperidone from immediate and controlled release buccal patches were found to be 129.7 ng·mL<sup>-1</sup>, 1.5 h, 455.1 ng·h·mL<sup>-1</sup> and 145.7 ng·mL<sup>-1</sup>, 5.25 h, 911.0 ng·h·mL<sup>-1</sup> respectively. A simple, sensitive and reliable method for the fluorescence determination of domperidone in human serum by UFLC method was developed and validated.
基金Supported by the National Natural Science Foundation of China(No.39930180).
文摘A rapid, sensitive, and accurate method based on LC/MS/MS was developed and validated for the determination of domperidone in human plasma. Domperidone and internal standard, tramadol, were extracted from plasma with di- ethyl ether-dichloromethane （60： 40, volume ratio） and separated by reversed-phase HPLC with methanol-water-am- monia solution（80： 20： 0.2, volume ratio） as the mobile phase. Detection was carried out v/a multiple-reaction moni-toting（MRM） on a Q-trap^TM LC/MS/MS system（Q-trap^TM）. The assay result was linear over a concentration range of 0.1-30 ng/mL with a limit of quantitation （LOQ） of 0.1 ng/mL. The inter-and inn＇a-day precision levels were within 7.52% and 12.9%, respectively, whereas the accuracy was within a range of 87.3%-114%. This method has been successfully applied to evaluate the pharmcokinetics of domperidone in Chinese healthy volunteers given an oral dose of 10 mg.
文摘Abstract： Commercially available domperidone -a D2 receptor antagonist- is an immediate release formulation which has never been formulated into microspheres for sustained release. The present work aims towards studying the effect of combination of a natural chitosan from an oyster shell of Mystilis edulis and HPMC （hydroxy propyl methyl cellulose） （spectracel 15 E） as polymer and tripolyphosphate as cross linking agent using wet gelation technique. The various polymer combination ratios for different batches were compared with a low molecular weight standard chitosan. The extracted chitosan - HPMC polymer combination ratios were chosen at ten levels： as batches B1, B2, B3, B4, B5, B6, B7, B8, B9, B10 for 1：1, 1：2, 2：1, 1：0, 0：1, 3：1, 1：3, 5：1, and 1：5 and 1：1 having 450：450, 300：600, 600：300, 900：0, 0：900, 675：225, 225：675, 750：150, 150：750, 450：450 mg respectively, while the quantity of domperidone and tripolyphosphate remained constant. B 11 and B 12 were formulated with standard chitosan and HPMC. The percentage yield of the formulated microspheres was determined and then evaluated for flowability, drug entrapment efficiency, drug release and mechanism of drug release by Fickian diffusion. The best batches of the domperidone loaded microspheres produced from the combination polymer were compared with the standard chitosan. The highest yields of microspheres were given by batches B12, B11, B10, and B4 with values of 50.1 ± 0.1%, 49.6 ± 0.1%, 46.6 ：± 0.1%, and 46.1 ± 0.0% respectively while the lowest yield were 23.3 ± 0.2% and 23.6 ± 0.2%. B5 and B6 and B9 did not yield any microsphere. The bulk density, tapped density, compressibility and Hausner＇s ratio of the microspheres showed good flowability and high percent compressibility. The drug entrapment efficiency showed that the entrapment ranged from 54.2 to 97.2, where the least entrapment was B4 （54.2 ± 0.1） and the highest B12 （97.2 ± 0.2）. The polymer surface of the microspheres as observed by SEM （scanning electron microscopy） was heterogeneous and porous which offers enhanced bioadhesivity. The dissolution study was used to determine the percentage drug release which ranged from 12.1% to 68.9% after 5 hours. Batches 1, 2, 3, 4, 7, and I 1 follow zero order kinetics via Fickian diffusion. The results indicate that microspberes of domperidone could be successfully formulated with a natural chitosan either alone or in combination with HPMC for sustained delivery of domperidone. Furthermore, the concentration of the natural polymer and HPMC employed in the formulation need to be carefully selected to enable the production of microspheres with the desired sustained release properties.
文摘Gastroeophageal reflux is a condition in which the acidified liquid content of the stomach backs up into the esophagus. The antiacid magaldrate and prokinetic domperidone are two drugs clinically used for the treatment of gastroesophageal reflux symptoms. However, the evidence of a superior effectiveness of this combination in comparison with individual drugs is lacking. A double-blind, randomized and comparative clinical trial study was designed to characterize the efficacy and safety of a fixed dose combination of magaldrate (800 mg)/domperidone (10 mg) against domperidone alone (10 mg), in patients with gastroesophageal reflux symptoms. One hundred patients with gastroesophageal reflux diagnosed by Carlsson scale were randomized to receive a chewable tablet of a fixed dose of magaldrate/domperidone combination or domperidone alone four times each day during a month. Magaldrate/domperidone combination showed a superior efficacy to decrease global esophageal (pyrosis, regurgitation, dysphagia, hiccup, gastroparesis, sialorrhea, globus pharyngeus and nausea) and extraesophageal (chronic cough, hoarseness, asthmatiform syndrome, laryngitis, pharyngitis, halitosis and chest pain) reflux symptoms than domperidone alone. In addition, magaldrate/domperidone combination improved in a statistically manner the quality of life of patients with gastroesophageal reflux respect to monotherapy, and more patients perceived the combination as a better treatment. Both treatments were well tolerated. Data suggest that oral magaldrate/domperidone mixture could be a better option in the treatment of gastroesophageal reflux symptoms than only domperidone.
文摘Domperidone Maleate (DOM), an antiemetic drug, has been used in treatment of adults and children. It has low aqueous solubility and hence low bioavailability. In present study, an attempt has been made to enhance the solubility of DOM by inclusion complexation with Hydroxypropyl-β-Cyclodextrin (HP-β-CD) using kneading technique and formulation of fast disintegrating tablets by using Sodium Starch Glycolate as superdisintegrant. Solubility analysis of DOM in different concentrations of HP-β-CD was carried out. Design of experiment (DOE) is done by using MINITAB 15.1 software to find out the variable for dissolution and disintegration time. HP-β-CD and SSG were identified as the variable for disintegration time and dissolution. For optimization of the concentration of HP-β-CD and SSG, two factors at two levels design through central composite design (CCD) were used which gave 13 formulations. All formulations are evaluated for characteristics such as weight variation, hardness, friability, disintegration time and dissolution of drug. Solubility of DOM increases linearly with increase in concentration of HP-β-CD. The optimum concentration of HP-β-CD is found to be in 1:2 molar ratios and SSG of 7%. The In-Vitro dissolution studies of optimized formulation and market sample were carried out in USP type II apparatus at different time intervals of 5, 10, 15 and 30 minutes at 50 rpm in 0.1 N HCl. The dissolution and disintegration time of optimized formulation is found better than market sample.
文摘Silica aerogel (SA) was loaded with domperidone to demonstrate the potentiality of adsorption processes based on the usage of supercritical carbon dioxide to treat poorly water-soluble drugs, forming new kinds of drug delivery systems. The effects of pressure, temperature and solution concentration on loaded SA were studied. Adsorption isotherms were measured at 35℃ and 45℃ and fitted with Langmuir model. Release kinetics of the adsorbed drug were also evaluated by in vitro dissolution tests. Results showed that domperidone can be uniformly dispersed into the aerogel and that the release rate of domperidone from the composite, constituted by drug and silica aerogel, is much faster than that of the crystalline drug. The proposed adsorption method is suitable for the production of domperidone fast release tablets.
