马来酸曲美布汀胃漂浮缓释片的处方筛选及体外评价

目的筛选马来酸曲美布汀胃漂浮缓释片的处方,并评价其漂浮和体外释放特性。方法用正交实验设计对片剂处方进行筛选与优化,制备马来酸曲美布汀胃漂浮缓释片,测定其体外释药与漂浮特性。结果优选的处方为每片含HPMC800030 mg,CMC-Na 30 mg,十六醇70 mg,CaCO330 mg。该处方片剂在硬度为3-4 kg时漂浮性好,体外持续释药达6 h以上,符合Higuchi模型。结论该片剂具漂浮、缓释作用,制备工艺简单。     

马来酸曲美布汀联合门诊森田疗法治疗肠易激综合征的临床研究

目的 :观察马来酸曲美布汀联合门诊森田疗法治疗肠易激综合征 (irritablebowelsyndrome ,IBS)的临床疗效。方法 :10 8例患者随机分为 2组。马来酸曲美布汀组 5 4例 :2 0 0mg马来酸曲美布汀 ,po ,tid ,配合门诊森田心理疗法 ,治疗前、后以焦虑自评量表 (SAS)和抑郁自评量表 (SDS)评定疗效 ;对照组5 4例 :仅用 2 0 0mg马来酸曲美布汀 ,po ,tid ,2组疗程均为 4周。结果 :马来酸曲美布汀组和对照组总有效率分别为 87.0 4 %与 72 .2 2 % ,马来酸曲美布汀组明显优于对照组 (P <0 .0 5 )。马来酸曲美布汀组治疗后SAS、SDS评分与对照组比较均有明显下降(P <0 .0 1)。马来酸曲美布汀组 6月复发率与对照组比较明显降低 (P <0 .0 1)。结论 :马来酸曲美布汀联合门诊森田疗法是治疗肠易激综合征更有效的治疗方法。     

马来酸曲美布汀治疗肝硬化患者胃电节律紊乱的临床疗效

目的分析肝硬化患者胃电图变化及马来酸曲美布汀治疗胃功能紊乱的有效性。方法95例患者按照肝功能分级分为2组，马来酸曲美布汀治疗前后对比，进行胃电图检查及症状分析。结果治疗后胃电图峰值幅度、胃电主频较治疗前明显改善（P〈0．05），治疗后患者症状明显改善。结论肝硬化患者胃蠕动和胃排空能力下降，予马来酸曲美布汀治疗能改善其胃电生理和临床症状。     

毛细管区带电泳法测定曲美布汀胶囊的含量

马来酸曲美布汀可直接作用于平滑肌[1] ,调节胃肠运动功能[2 ] ,是具有独特的双向调节作用的新型胃功能调节剂[3] ,即消化系统功能低下时可增强其功能 ,消化系统功能亢进时则抑制其功能。马来酸曲美布汀原料药的分析测定方法主要有薄层色谱法[4 ] 、非水滴定法[5] 、ＨＰＬＣ法[5] ;其片剂的分析测定方法有紫外分光光度法[6 ] 等。马来酸曲美布汀胶囊为一新制剂 ,本文采用毛细管区带电泳法(ＣＺＥ)测定其中马来酸曲美布汀的含量。1　仪器与试药ＧＤＹ - 30ｋＶ型毛细管电泳高压电源仪 (山东大学化学院 ) ;Ｓｐｅｃｔｒａ - 10 0可变波长检测…     

HPLC法测定马来酸曲美布汀缓释片中的有关物质和含量

目的使用高效液相色谱(HPLC)仪建立一种测定马来酸曲美布汀缓释片中的有关物质及含量方法。方法用反相高效液相色谱法,流动相为乙腈:0.05mol/L磷酸二氢钾溶液(pH=4)(40∶60,V∶V);流速:0.8 mL/min;柱温:25℃;检测波长为254nm。结果缓释片中的辅料对马来酸曲美布汀的测定无干扰,有关物质与主药的分离度良好且符合要求。马来酸曲美布汀在2～40mg/L范围内线性关系良好,以曲美布汀的峰面积对浓度进行线性回归,方程为A=22345c+1408,r=0.9997;日内、日间精密度RSD均<2%;平均回收率均在98.5%～101.5%之间。结论高效液相色谱法的准确度、精密度、重现性等均符合中国药典规定,可用于马来酸曲美布汀缓释片的含量测定及有关物质检查。     

马来酸曲美布汀分散片的制备及质量控制

目的 制备马来酸曲美布汀分散片,并进行质量控制.方法采用紫外分光光度法测定马来酸曲美布汀的含量;高效液相色谱法进行样品有关物质检查;通过改变不同因素进行马来酸曲美布汀分散片的工艺筛选,并按中国药典2005年版二部附录进行分散均匀性检查、崩解时限检查和溶出度检查.结果优化处方为马来酸曲美布汀100g,PVPP 80g,微晶纤维素100 g,阿司巴甜1.0 g,硬脂酸镁0.5g,桔子香精适量,8%淀粉浆(含1%十二烷基硫酸钠),共制成1 000片.结论 优化后分散片的片重差异、溶出度和崩解时间均符合中国药典的规定,有关物质和含量亦符合本品临床用药的质量标准(草案).     

马来酸曲美布汀联合谷维素治疗肠易激综合征的效果观察

目的：观察马来酸曲美布汀联合谷维素治疗肠易激综合征的临床效果。方法将66例肠易激综合征患者随机分为治疗组和对照组各33例。对照组患者采用马来酸曲美布汀治疗,治疗组患者采用马来酸曲美布汀联合谷维素治疗,对2组患者的治疗效果进行观察对比。结果治疗组患者的治疗总有效率显著高于对照组,不良反应发生率明显低于对照组,差异均有统计学意义（P＜0．05）。结论对肠易激综合征患者采用马来酸曲美布汀联合谷维素进行治疗,能有效提高临床疗效,降低不良反应发生率,值得临床推广。     

马来酸曲美布汀平衡溶解度及其缓释微丸释放度的pH依赖性

<正>马来酸曲美布汀(trimebutine maleate,TMB)是新型胃功能调节剂,主治胃肠道功能紊乱性疾病,如肠易激惹综合征(IBS)、慢性胃炎所致的胃肠道功能紊乱和手术后肠道功能紊乱等[1]。马来酸曲美布汀直接作用于胃内平滑肌,延长其在胃内的滞留时间可增加其作用强度[2]。目前市场其主要剂型有     

马来酸曲美布汀缓释片体外释药影响因素的考察

目的研究马来酸曲美布汀缓释片的体外释药影响因素。方法以紫外分光光度法为分析方法,研究马来酸曲美布汀缓释片体外释放度。结果马来酸曲美布汀缓释片的体外释药符合Higuchi和Ritger Peppas释放规律,释药速率受HPMC的规格及用量、乳糖用量、制片工艺、片剂硬度等各种因素的影响。结论体外释药规律符合缓释制剂要求,可进一步进行体内释药行为考察。     

马来酸曲美布汀与埃索美拉唑联合治疗胃食管反流病的临床疗效及安全性分析

目的探讨马来酸曲美布汀与埃索美拉唑联合治疗胃食管反流病的临床疗效及安全性。方法68例胃食管反流病患者,通过抽签的方式分为对照组和实验组,每组34例。对照组实施埃索美拉唑治疗,实验组实施马来酸曲美布汀与埃索美拉唑联合治疗。比较两组治疗效果、不良反应发生率。结果实验组治疗总有效率为97.06%,高于对照组的82.35%,差异有统计学意义(P<0.05)。对照组不良反应发生率为8.82%,与实验组的11.76%比较,差异无统计学意义(χ^2=0.159,P=0.690>0.05)。结论在胃食管反流病患者的用药治疗中,马来酸曲美布汀与埃索美拉唑联合治疗具有良好的治疗效果以及用药安全性,值得推广。     

甲硝唑生物粘附微球的体外释药及其粘附性

目的研制具有良好粘附性能和缓释效果的甲硝唑生物粘附微球(Metro-EC-CP微球)。方法通过液中干燥法制备Metro-EC-CP微球。对微球理化性质、体外释药及在SD大鼠体内胃粘膜上的粘附性进行了研究。结果 微球的平均粒径为559.87 μm。体外释药符合一级动力学。微球的释药速率随着粒径的增加及载药量的减少而减慢。Metro-EC-CP微球中粘附性材料CP含量增加,其生物粘附性能增加,而其缓释效果降低。结论乙基纤维素(EC)-卡波姆934P(CP)为17∶3、载药量为25%的微球在动物体内具有良好的胃粘膜粘附性能,药物缓释达8 h。     

Mucoadhesive microsphere based suppository containing granisetron hydrochloride for management of emesis in chemotherapy

The purpose of present work was to develop suppositories containing mucoadhesive microspheres of granisetron hydrochloride (GH) using combination of xanthan gum and sodium alginate. Twelve different batches of microspheres containing GH were prepared by simple emulsification method and evaluated for surface morphology, particle size, equilibrium swelling degree, drug content, in vitro mucoadhesion, and in vitro drug release. The suppositories containing optimized batch of microspheres (C2) were formulated by fusion method using hydrophilic and lipophilic polymer base. The suppositories were evaluated for weight variation, hardness, macromelting range, drug content, drug release, morphology of rectal tissues, and in vivo suppository localization. Results show that, all microsphere batches were spherical and had size range 23.56–36.76 μm. The % drug encapsulation was found in the range 61.67–92.30 %, and showed satisfactory mucoadhesion. Especially, C2 batch had 83.67 % mucoadhesion and 92.30 % drug encapsulation and showed release retardation for 4 h. The results of all suppositories were within the pharmacopoeial standard limits. Drug content of all the suppositories was in the range 93.20–98.40 %. The suppository batch (P2M) was considered best on the basis of optimum retardation up to 5 h, high drug content, optimum mechanical strength and zero order release (r² = 0.9860). The suppository of batch P2M showed no morphological changes in rectal tissues indicating its safety. In vivo localization revealed satisfactory mucoadhesion of microspheres. Hence, it can be concluded that, delivery of GH in suppository form can avoid its presystemic metabolism, thus, may be an efficient alternative to its oral dosage form and conventional suppository.     

Development and characterization of mucoadhesive microspheres for nasal delivery of ketorolac

The objective of the present investigation was to prepare mucoadhesive microspheres of ketorolac for nasal administration by means of a solvent evaporation technique using carbopol (CP), polycarbophil (PL) and chitosan (CS) as mucoadhesive polymers. The prepared microspheres were characterized for morphology, swelling behavior, mucoadhesion, interaction studies, drug encapsulation efficiency, in vitro drug release, release kinetics, and ex vivo nasal cilio toxicity studies. The effects of various process variables on the particle size of the microspheres were investigated. Drug encapsulation efficiency and particle size of the microspheres ranged from 52-78% w/w and 14-46 microm respectively. Interaction studies revealed that there were no drug-polymer interactions. The in vitro release profiles showed prolonged-release of the drug. In vitro release data showed a good fit with the Higuchi model, and indicated Fickian diffusion. No severe damage was found to the integrity of nasal mucosa after ex vivo experiments.     

Evaluation of pH triggers in situ porous controlled release micro balloon delivery of amoxicillin for eradication of Helicobacter pylori

Helicobacter pylori reside in the gastric mucus layer and at the mucus-epithelial cell interface wherein access of antimicrobial drug to the infection site is restricted both from the stomach and from the gastric blood supply. The aim of the present study was to develop pectin or gellan gum blended sodium alginate microspheres in order to eradicate gastric Helicobacter pylori. The percentage drug release and mucoadhesion were decrease on increasing the calcium chloride in the formulation dispersion. Curing time significantly effected encapsulation efficiency and was not affected % drug content, % buoyancy, and particle size and drug release. The efficacy of the optimized formulation was evidenced by absence of amplified bacterial gene in treated stomach tissue of Mongolian gerbils as observed using in polymerase chain reaction. The results demonstrate that the developed formulation of Am has potential to eradicate Helicobacter pylori by targeted and prolonged retention at gastric mucosa.     

Preparation and In Vitro Characterization of Mucoadhesive Hydroxypropyl Guar Microspheres Containing Amlodipine Besylate for Nasal Administration

Amlodipine besylate microspheres for intranasal administration were prepared with an aim to avoid first-pass metabolism, to achieve controlled blood level profiles and to improve therapeutic efficacy. Hydroxypropyl Guar, a biodegradable polymer, was used in the preparation of microspheres by employing water in oil emulsification solvent evaporation technique. The formulation variables were drug concentration, emulsifier concentration, temperature, agitation speed and polymer concentration. All the formulations were evaluated for particle size, particle shape and surface morphology by scanning electron microscopy, percentage yield, drug entrapment efficiency, in vitro mucoadhesion test, degree of swelling and in vitro drug diffusion through sheep nasal mucosa. The microspheres obtained were free flowing, spherical and the particles ranged in size from 13.4±2.38 μm to 43.4±1.92 μm very much suitable for nasal delivery. Increasing polymer concentration resulted in increased drug entrapment efficiency and increased particle size. Amlodipine besylate was entrapped into the microspheres with an efficiency of 67.2±1.18 % to 81.8±0.64 %. The prepared microspheres showed good mucoadhesion properties, swellability and sustained the release of the drug over a period of 8 h. The data obtained were analysed by fitment into various kinetic models; it was observed that the drug release was matrix diffusion controlled and the release mechanism was found to be non-Fickian. Stability studies were carried out on selected formulations at 5±3°, 25±2°/60±5% RH and 40±2°/75±5% RH for 90 days. The drug content was observed to be within permissible limits and there were no significant deviations in the in vitro mucoadhesion and in vitro drug diffusion characteristics.     

Micromeritics and release behaviours of cellulose acetate butyrate microspheres containing theophylline prepared by emulsion solvent evaporation and emulsion non-solvent addition method

The present research work compares the effect of microsphere preparation technique on micromeritics and release behaviors of theophylline microspheres. Microspheres were prepared by oil-in oil (O₁/O₂) emulsion solvent evaporation method (ESE) using different ratios of anhydrous theophylline to cellulose acetate butyrate (CAB). Cyclohexane was used as non-solvent to modify the ESE technique (MESE method) and the effect of non-solvent volume on properties of microspheres was investigated. The obtained microspheres were analyzed in terms of drug content, particle size and encapsulation efficiency. The morphology of microsphere was studied using scanning electron microscope. The solid state of microspheres, theophylline and CAB were investigated using X-ray, FT-IR and DSC. The drug content of microspheres prepared by MESE method was significantly lower (15.54% ± 0.46) than microspheres prepared by ESE method (41.08 ± 0.40%). The results showed that as the amount of cyclohexane was increased from 2 mL to 6 mL the drug content of microspheres was increased from 15.54% to 28.71%. Higher encapsulation efficiencies were obtained for microspheres prepared by ESE method (95.87%) in comparison with MESE method (64.71%). Mean particle size of microsphere prepared by ESE method was not remarkably affected by drug to polymer ratio, whereas in MSES method when the volume of cyclohexane was increased the mean particle size of microsphere was significantly decreased. The ratio of drug to polymer significantly changed the rate of drug release from microspheres and the highest drug release was obtained for the microsphere with high drug to polymer ratio. The amount of cyclohexane did not significantly change the drug release. Although, x-ray showed a small change in crystallinity of theophylline in microspheres, DSC results proved that theophylline in microspheres is in amorphous state. No major chemical interaction between the drug and polymer was reported during the encapsulation process.     

Formation and in-vitro evaluation of theophylline-loaded poly(methyl methacrylate) microspheres

Theophylline-loaded poly(methyl methacrylate) (PMM) microspheres were prepared by the solvent evaporation method. Increasing the drug to polymer ratio increased both the mean particle size of the microspheres and the release rate. Polyethylene glycol (PEG) 4000 was used to improve the release rate of theophylline from the microspheres. No marked effect was observed on particle size distribution of the microspheres as a function of PEG concentration but there was a pronounced effect on drug release. The different particle sizes of microspheres prepared from the same drug to polymer ratio showed no significant difference in drug content, indicating that the ratio between theophylline and PMM remained practically constant regardless of the size of microspheres. Release characteristics of the microspheres were influenced by drug to polymer ratio, the amount of PEG incorporated and the particle size of microspheres. The release rate was slightly higher in simulated gastric fluid than in simulated intestinal fluid. The release profiles of the drug were modified by mixing microspheres of different formulations in different ratios.     

Cyclophosphamide loaded albumin microspheres II. Release characteristics

The purpose of this investigation was to evaluate the release characteristics of cyclophosphamide (CP) from glutaraldehyde stabilized human serum albumin microspheres, and to study the effect of the extent of cross-linking, the amount of the stabilizing agent and the size of the microspheres on the in vitro release of CP. Microspheres were prepared by emulsion polymerization method using two different volumes (0.1 and 0.7 ml) of glutaraldehyde solution (25 per cent) and two different crosslinking durations (15 min and 1 h). The resulting mean particle size of the microspheres also varied between 2.5 microns and 3.7 microns. The total CP content in microspheres was analysed from the surface drug and the entrapped drug.     

Formulation and evaluation of stomach-specific amoxicillin-loaded carbopol-934P mucoadhesive microspheres for anti-Helicobacter pylori therapy

The purpose of this research was to formulate and systemically evaluate in vitro and in vivo performances of mucoadhesive amoxicillin microspheres for the potential use in the treatment of gastric and duodenal ulcers, which were associated with Helicobacter pylori. Amoxicillin mucoadhesive microspheres containing carbopol-934P as mucoadhesive polymer and ethyl cellulose as carrier polymer were prepared by an emulsion-solvent evaporation technique. Results of preliminary trials indicate that quantity of emulsifying agent, time for stirring, drug-to-polymers ratio and speed of rotation affected the characteristics of microspheres. Microspheres were discrete, spherical, free flowing and showed a good percentage of drug entrapment efficiency. An in vitro mucoadhesive test showed that amoxicillin mucoadhesive microspheres adhered more strongly to the gastric mucous layer and could retain in the gastrointestinal tract for an extended period of time. A 3(2) full factorial design was employed to study the effect of independent variables, drug-to-polymer-to-polymer ratio (amoxicillin-ethyl cellulose-carbopol-934P) (X(1)) and stirring speed (X(2)) on dependent variables, i.e. percentage mucoadhesion, drug entrapment efficiency, particle size and t(80). The best batch exhibited a high drug entrapment efficiency of 56%; mucoadhesion percentage after 1 h was 80% and the particle size was 109 μm. A sustained drug release was obtained for more than 12 h. The drug-to-polymer-to-polymer ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive microspheres were studied under a scanning electron microscope. In vitro release test showed that amoxicillin released slightly faster in pH 1.2 hydrochloric acid than in pH 7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering amoxicillin powder and mucoadhesive microspheres to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in oral administration. The results showed that amoxicillin mucoadhesive microspheres had a better clearance effect than amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make a contribution to H. pylori complete eradication.     

Stomach specific anti-helicobacter pylori therapy: preparation and evaluation of amoxicillin-loaded chitosan mucoadhesive microspheres

The purpose of this research was to formulate and systematically evaluate in vitro and in vivo performances of mucoadhesive amoxicillin microspheres for the potential use of treating gastric and duodenal ulcers, which were associated with Helicobacter pylori. Amoxicillin mucoadhesive microspheres containing chitosan as mucoadhesive polymer were prepared by simple emulsification phase separation technique using glutaraldehyde as a cross-linking agent. Results of preliminary trials indicate that volume of cross-linking agent, time for cross-linking, polymer-to-drug ratio, and speed of rotation affected characteristics of microspheres. Microspheres were discrete, spherical, free flowing and also showed high percentage drug entrapment efficiency. In vitro mucoadhesive test showed that amoxicillin mucoadhesive microspheres adhered more strongly to gastric mucous layer and could retain in gastrointestinal tract for an extended period of time. A 3(2) full factorial design was employed to study the effect of independent variables, polymer-to-drug ratio (X(1)), and stirring speed (X(2)) on dependent variables i.e. percentage mucoadhesion, t(80), drug entrapment efficiency, particle size and swelling index. The best batch exhibited a high drug entrapment efficiency of 70 % and a swelling index of 1.39; percentage mucoadhesion after 1 h was 79 %. The drug release was also sustained for more than 12 h. The polymer-to-drug ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive microspheres were studied using scanning electron microscopy. In vitro release test showed that amoxicillin released slightly faster in pH 1.0 hydrochloric acid than in pH 7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering amoxicillin mucoadhesive microspheres and powder, to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in oral administration. The results showed that amoxicillin mucoadhesive microspheres had a better clearance effect than amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make contribution complete eradication of H. pylori.