盐酸多西环素调释微丸的制备及处方因素考察

选用HPMCP-55和HPMC E15作为包衣材料,制备盐酸多西环素调释微丸,并考察其处方因素和工艺.采用流化床底喷溶液上药法制备载药微丸,考察聚合物HPMCP-55和致孔剂HPMC E15之间的比例,聚合物包衣增重以及增塑剂用量和热处理对药物释放的影响.当HPMCP-55和HPMC E15的质量比为25:4,聚合物包衣增重为10%,增塑剂用量为5%时,药物释放行为符合要求.通过调整HPMCP-55和HPMC E15之间的比例,或选择恰当的包衣增重,能使盐酸多西环素载药微丸具备较理想的释放效果.     

氧化苦参碱缓释微丸的制备及包衣处方因素的考察

目的:探讨制备氧化苦参碱缓释微丸的影响因素。方法:以挤出滚圆法制备含药丸芯,采用流化床包衣法,分别以HPMC E5及Eudragit RS 30D作为隔离层及控释层的包衣材料进行包衣,考察隔离层包衣增重,控释层增塑剂的种类、用量,以及包衣增重对微丸释放行为的影响。结果:优选出以2%的HPMC E5作为隔离层包衣液,并加入0.2%的PEG 400作为增塑剂,隔离层包衣增重10%;控释层包衣处方为Eudragit RS 30D 6%,滑石粉2%,增塑剂邻苯二甲酸二丁酯(DBP)2%,水90%,包衣增重10%。所制备的氧化苦参碱缓释微丸与普通微丸相比,表现出明显的缓释行为。结论:该工艺处方所制备的氧化苦参碱缓释微丸具有良好的缓释特性。     

星点设计-效应面法优化鱼腥草素钠缓释片的处方

目的 应用星点设计-效应面法优化鱼腥草素钠缓释片的处方.方法 以HPMC和EC的用量为考察因素,分别以鱼腥草素钠在1, 4, 8和12 h的累积释放度为指标,采用星点设计-效应面优化法,确定优化处方区域,并进行优化处方的验证分析. 结果最优处方区域为HPMC 42～62 mg和EC 5.8～6.6 mg,优化处方的考察...     

肠必清肠溶颗粒包衣处方及制备工艺研究

目的:优选肠必清肠溶颗粒制备工艺。方法:采用正交试验设计,考察丙烯酸树脂浓度和蓖麻油、滑石粉、甲基硅油用量4种因素对肠溶颗粒收率的影响;采用释放度试验,考察肠溶颗粒增塑剂蓖麻油用量及包衣增重量。结果:包衣液处方丙烯酸树脂浓度为5%,蓖麻油相对丙烯酸树脂用量为35%,滑石粉及甲基硅油用量分别为3%、1%,包衣增重为30%,即为最佳制剂工艺。结论:由最佳工艺制备的肠必清肠溶颗粒质量符合要求,具有理想的肠溶释药特性。     

泼尼松脉冲片的制备研究

目的制备泼尼松脉冲片并考察其在体外的释放特性。方法采用粉末直接压片法制备速释片芯,以羟丙甲纤维素(HPMC)为溶胀层包衣材料,以乙基纤维素(EC)为控释层包衣材料,采用多层包衣技术制备泼尼松脉冲片。考察了致孔剂PEG 400、增塑剂PEG 6000比例与用量以及控释层包衣增重对释放的影响。以迟滞时间和累积释放度为指标,考察泼尼松脉冲片的体外释放特性。结果以片芯崩解剂用量为11%,致孔剂用量为10%,增塑剂用量为1%,溶胀层和控释层包衣分别增重为5%、10.5%制备的泼尼松脉冲片效果最佳。按照最优处方工艺制备的泼尼松脉冲片体外释放迟滞时间为4 h,时滞后0.5~1.0 h累积释放度达95%以上。结论泼尼松脉冲片处方组成合理,工艺简便可行,体外释放特性符合脉冲释放设计要求。     

甲磺酸倍他司汀微孔渗透泵控释片包衣处方的优化

目的:制备甲磺酸倍他司汀微孔渗透泵控释片,并对其包衣处方进行优化。方法:采用相似因子法考察影响释药的主要因素,采用正交试验以致孔剂聚乙二醇的用量、增塑剂邻苯二甲酸二丁酯(DBP)的用量和包衣增重为因素,以释放度的综合指标L值为指标优化包衣处方,并进行验证试验及体外释药模型拟合。结果:相似因子值均小于50,表明聚乙二醇、DBP的用量及包衣增重对制剂的释放均有显著影响;优化的最佳包衣处方中聚乙二醇为30%,DBP为20%,包衣增重为4%;验证试验中3批样品L值分别为13.99、11.15、8.37,12h累积释药百分率大于90%,释药模型特征为零级释药。结论:按最佳处方制得的甲磺酸倍他司汀微孔渗透泵控释片在12h内可稳定释药,且释放完全。     

右旋雷贝拉唑钠肠溶微丸的制备及体外释放度考察

目的:制备右旋雷贝拉唑钠肠溶微丸,并考察其体外释放度。方法:采用流化床底喷包衣技术制备右旋雷贝拉唑钠上药微丸,再用HPMC E5包隔离衣,最后使用丙烯酸树脂L30D-55包肠溶衣,制成右旋雷贝拉唑钠肠溶微丸。并比较自研制剂与参比制剂体外释放度的相似性。结果:右旋雷贝拉唑钠肠溶微丸包衣处方为:HPMC E5隔离衣层增重为12.0%,丙烯酸树脂L30D-55肠溶衣层增重为45.0%,增塑剂用量为聚合物重量的8.0%。体外释放度结果显示,自研制剂和参比制剂f₂相似因子大于50,说明两种制剂体外释放行为相似。结论:制备的右旋雷贝拉唑钠肠溶微丸的释药行为较好,有望应用于工业生产。     

星点设计-效应面法优化阿昔莫司控释片处方研究

目的优化阿昔莫司控释片处方。方法以PEG4000的用量和包衣增重为考察因素,应用星点设计-优化面效应法优化阿昔莫司控释片处方。结果优化处方工艺参数为:包衣材料中PEG4000的用量为28.25%,包衣增重7.40%。结论本实验确定的处方方法合理,稳定可行。     

星点设计-效应面法优化复方氯雷伪麻缓释片的缓释片芯处方

目的:优化复方氯雷伪麻缓释片的缓释片芯处方。方法:以氯雷他定加入包衣层并包衣硫酸伪麻黄碱片芯制备复方氯雷伪麻缓释片。采用星点设计-效应面法优化硫酸伪麻黄碱片芯处方,以单硬脂酸甘油酯(GM)和羟丙甲纤维素(HPMC)K15M用量为考察因素,以硫酸伪麻黄碱1、6、12 h的累积释放度为指标,通过重叠等高线图确定优化处方,并进行处方验证。结果:氯雷他定与欧巴代包衣粉按1∶3比例混合包衣成为速释层;硫酸伪麻黄碱片芯作为缓释层,其处方为每100片(600 mg/片)含硫酸伪麻黄碱12 g、GM 16.72 g、HPMC K15M 20.95 g、微晶纤维素9.73 g、硬脂酸镁0.6 g。优化处方所制制剂中氯雷他定15 min的累积溶出度为87.2%,硫酸伪麻黄碱1、6、12 h的累积释放度分别为34.20%、74.32%、94.60%。结论:缓释片芯处方合理、可行,所制备的复方氯雷伪麻缓释片具有缓释作用。     

间尼索地平微孔渗透泵微丸的制备及释药机制研究

目的:制备间尼索地平微孔渗透泵微丸,并探讨其释药机制。方法:以磺丁基醚-β-环糊精(SBE-β-CD)为渗透压物质,采用挤出滚圆法制备丸芯,流化床包衣法包衣;以累积释放度为指标,通过单因素法考察增塑剂癸二酸二丁酯(DBS)用量、包衣增重、包衣液(醋酸纤维素的丙酮-异丙醇溶液)浓度对微丸释放的影响,优选包衣处方。按最优处方制备3批微丸并以累积释放度与时间进行零级、一级、Higuchi方程拟合来考察其释药特征。结果:增塑剂用量为15%,包衣增重为4%,包衣液浓度为1%;所制备的间尼索地平微孔渗透泵微丸12h内释药具有零级释放特征(r=0.9996,0.9995,0.9989),释放动力以渗透压为主。结论:该制备工艺稳定、重现性良好,12h内释药恒定。     

白术黄连微丸结肠靶向胶囊的制备及体外释放研究

目的 将中药"白术黄连方"制备成以胃溶微丸和肠溶微丸为基础的结肠靶向胶囊,优化其处方组成和制备工艺,考察其体外释放特性.方法 采用单因素实验和正交实验法优化微丸的处方组成和工艺参数.用挤出-滚圆技术制备素丸,流化床底喷方式进行包衣,考察隔离衣增重、肠溶衣中聚合物比例、增塑剂用量和包衣增重对肠溶微丸释放行为的影响,并对其...     

Controlled Release Multiparticulate Beads Coated with Starch Acetate: Material Characterization,and Identification of Critical Formulation and Process Variables

The objectives of the present investigation were to prepare and characterize starch acetate (SA) with high degree of substitution (dS) and to study its prospect as film-forming agent in a controlled-release multiparticulate drug delivery system. As a part of the development process by quality by design, the objectives also included identification of critical formulation and process variables that affect the release of a drug. SA, a relatively new polymer, was characterized because it showed good film-forming properties. SA with dS 2.9 was synthesized from corn starch by paste disruption technique. It was compared with the raw material, starch, by Fourier transform infrared spectroscopy, X-ray diffraction, and molecular mass analysis. Viscosity of SA solution increased logarithmically with the polymer concentration. At higher polymer concentrations (1.5–5.0%), the solutions showed pseudoplastic behavior. Among the plasticizers tested, triacetin and triethyl citrate yielded free films with acceptable mechanical properties. The glass transition temperature (T_g) of the films could be well controlled by these plasticizers. Unplasticized film showed a T_g of 31.8°C. A trend was found that increase in triacetin concentration in SA films resulted in increase in permeability coefficient for tritiated water. Scanning electron microscopic photographs showed a clear and smooth plasticized film compared to rough unplasticized film. Dyphylline-loaded beads were coated with highly substituted SA to evaluate the main effects of the formulation and process variables on the release of the drug and to figure out the reliability of the screening design. A seven-factor, twelve-run Plackett-Burman screening design was used. The response variables were cumulative percent of drug released in 0.5, 1, 4, 8, and 12 hr. Quantitative evaluation of the design revealed that coating weight gain, plasticizer concentration, and post-drying temperature had greater influence on the drug release than the others. The main effects on drug release after 12 hr decreased in the following order: coating weight gain (?7.81), plasticizer concentration (4.96), postdrying temperature (?2.51), SA concentration (?0.80), inlet temperature (0.51), postdrying time (?0.31), and atomizing pressure (?0.28).     

Controlled release multiparticulate beads coated with starch acetate: material characterization, and identification of critical formulation and process variables

The objectives of the present investigation were to prepare and characterize starch acetate (SA) with high degree of substitution (dS) and to study its prospect as film-forming agent in a controlled-release multiparticulate drug delivery system. As a part of the development process by quality by design, the objectives also included identification of critical formulation and process variables that affect the release of a drug. SA, a relatively new polymer, was characterized because it showed good film-forming properties. SA with dS 2.9 was synthesized from corn starch by paste disruption technique. It was compared with the raw material, starch, by Fourier transform infrared spectroscopy, X-ray diffraction, and molecular mass analysis. Viscosity of SA solution increased logarithmically with the polymer concentration. At higher polymer concentrations (1.5-5.0%), the solutions showed pseudoplastic behavior. Among the plasticizers tested, triacetin and triethyl citrate yielded free films with acceptable mechanical properties. The glass transition temperature (Tg) of the films could be well controlled by these plasticizers. Unplasticized film showed a Tg of 31.8 degrees C. A trend was found that increase in triacetin concentration in SA films resulted in increase in permeability coefficient for tritiated water. Scanning electron microscopic photographs showed a clear and smooth plasticized film compared to rough unplasticized film. Dyphylline-loaded beads were coated with highly substituted SA to evaluate the main effects of the formulation and process variables on the release of the drug and to figure out the reliability of the screening design. A seven-factor, twelve-run Plackett-Burman screening design was used. The response variables were cumulative percent of drug released in 0.5, 1, 4, 8, and 12 hr. Quantitative evaluation of the design revealed that coating weight gain, plasticizer concentration, and post-drying temperature had greater influence on the drug release than the others. The main effects on drug release after 12 hr decreased in the following order: coating weight gain (-7.81), plasticizer concentration (4.96), postdrying temperature (-2.51), SA concentration (-0.80), inlet temperature (0.51), postdrying time (-0.31), and atomizing pressure (-0.28).     

Influence of Plasticizer Level on the Drug Release from Sustained Release Film Coated and Hot-Melt Extruded Dosage Forms

In the current study, the influence of plasticizer level on drug release was investigated for solid dosage forms prepared by hot-melt extrusion and film coating. The properties of two highly water-soluble compounds, diltiazem hydrochloride (DTZ) and chlorpheniramine maleate (CPM), and a poorly water-soluble drug, indomethacin (IDM), were investigated in the melt extrudates containing either Eudragit® RSPO or Eudragit® RD 100 and triethyl citrate (TEC) as the plasticizer. In addition, pellets containing DTZ were film coated with Eudragit® RS 30D and varying levels of TEC using a fluidized bed coating unit. Differential scanning calorimetry (DSC) demonstrated that both CPM and IDM exhibited a plasticization effect on the acrylic polymers, whereas no plasticizing effect by DTZ on Eudragit® RSPO was observed. Thermogravimetric analysis (TGA) was used to investigate the thermal stability of the DTZ, Eudragit® RSPO and TEC at 140 °C, the maximum temperature used in the hot-melt extrusion process. The chemical stability of DTZ and IDM in the extrudate following hot-melt processing was determined by high pressure liquid chromatography (HPLC). Drug release rates of both DTZ and CPM from hot-melt extrudates increased with an increase in the TEC level in the formulations, while the release rate of DTZ from the Eudragit® RS 30D–coated pellets decreased with an increase in TEC in the coating dispersion. This phenomenon was due to the formation of a reservoir polymeric structure as a result of the thermal stress and shear stress involved in the hot-melt extrusion process regardless of the TEC level. In contrast, coalescence of the polymer particles in the film coating process was enhanced with higher levels of TEC, as demonstrated by scanning electron microscopy (SEM). The addition of TEC (0% to 8%) in the IDM hot-melt extrudate formulation had no influence on the drug release rate as the drug release rate was controlled by drug diffusion through the inside of the polymeric materials rather than between the polymer particles.     

奥沙西罗包衣控释片的制备及其质量评价

目的制备奥沙西罗包衣控释片,考察处方组成和工艺因素对制剂质量及体外释药行为的影响,并分析其释药机制。方法以乙基纤维素(EC-45cP)为骨架材料、乙基纤维素(EC-10cP)为成膜材料、聚乙二醇6000(PEG6000)为增塑剂,采用滚转包衣锅包衣,药物作为致孔剂控制药物释放,考察处方因素,片芯制备和包衣工艺等对制剂质量及体外释放行为的影响。结果片芯骨架材料用量、致孔剂用量、增塑剂用量、包衣厚度等因素对药物释放有明显影响。制剂体外释药行为符合零级动力学方程。结论薄膜包衣法制得奥沙西罗控释片,调整处方组成可获得12 h平稳释药的制剂。     

Influence of plasticizer level on the drug release from sustained release film coated and hot-melt extruded dosage forms

In the current study, the influence of plasticizer level on drug release was investigated for solid dosage forms prepared by hot-melt extrusion and film coating. The properties of two highly water-soluble compounds, diltiazem hydrochloride (DTZ) and chlorpheniramine maleate (CPM), and a poorly water-soluble drug, indomethacin (IDM), were investigated in the melt extrudates containing either Eudragit RSPO or Eudragit RD 100 and triethyl citrate (TEC) as the plasticizer. In addition, pellets containing DTZ were film coated with Eudragit RS 30D and varying levels of TEC using a fluidized bed coating unit. Differential scanning calorimetry (DSC) demonstrated that both CPM and IDM exhibited a plasticization effect on the acrylic polymers, whereas no plasticizing effect by DTZ on Eudragit RSPO was observed. Thermogravimetric analysis (TGA) was used to investigate the thermal stability of the DTZ, Eudragit RSPO and TEC at 140 degrees C, the maximum temperature used in the hot-melt extrusion process. The chemical stability of DTZ and IDM in the extrudate following hot-melt processing was determined by high pressure liquid chromatography (HPLC). Drug release rates of both DTZ and CPM from hot-melt extrudates increased with an increase in the TEC level in the formulations, while the release rate of DTZ from the Eudragit RS 30D-coated pellets decreased with an increase in TEC in the coating dispersion. This phenomenon was due to the formation of a reservoir polymeric structure as a result of the thermal stress and shear stress involved in the hot-melt extrusion process regardless of the TEC level. In contrast, coalescence of the polymer particles in the film coating process was enhanced with higher levels of TEC, as demonstrated by scanning electron microscopy (SEM). The addition of TEC (0% to 8%) in the IDM hot-melt extrudate formulation had no influence on the drug release rate as the drug release rate was controlled by drug diffusion through the inside of the polymeric materials rather than between the polymer particles.     

西罗莫司单层高分子渗透泵控释片的制备及其体外释放特性研究

目的:制备西罗莫司单层高分子渗透泵控释片并考察其体外释放特性。方法:通过对片芯组成中的释药载体聚氧乙烯(PEO)的分子量、用量,促渗剂种类及氯化钠(NaCl)用量,包衣液中的聚乙二醇400(PEG400)用量,衣膜增重等设计单因素试验进行初步筛选,在此基础上以NaCl用量、衣膜增重、PEG400用量为因素,以释药方程的相关系数r为评价指标设计正交试验,考察并优化制剂处方及工艺,同时对其体外释放特性进行评价。结果:以PEO(Mw20000)30mg、NaCl70mg为片芯辅料,PEG4000.14g为包衣材料,衣膜增重12mg时制得的片剂最优,其零级释放特征显著,r=0.9954。结论:该制剂制备工艺简单,在体外可近恒速缓慢释放药物。     

Tablet film-coating with amylose-rich maize starch.

The purpose of the present study was to investigate an aqueous-based amylose-rich maize starch (Hylon VII) film-coating process of tablets performed by a side-vented pan coating system. Three formulation or process parameters of potential importance, including the plasticizer concentration (X(1)), the temperature of coating pan (X(2)) and the spray rate of the coating solution (X(3)), were evaluated using a central composite face-centred experimental design. Only a few process-related limitations associated with the aqueous film coating of Hylon VII were observed, and, in general, the coated tablets were of fairly good quality. At low spray rates, the temperature of the coating pan did not affect the roughness of the coated tablets. At higher spray rates, higher temperature gave smoother films. As regards surface quality and smoothness, a plasticizer concentration (i.e., a 1:1 mixture of sorbitol and glycerol) of approximately 65% of the polymer weight, seems to be suitable for the present formulations. The dissolution of all Hylon VII-coated tablets in an acidic medium was rapid, more than 75% of the drug (theophylline) dissolved within 15 min. On the basis of the present results, it can be concluded that amylose-rich maize starch (Hylon VII) may be considered as an aqueous film-coating agent to be used for pharmaceutical purposes and in established film-coating processes.     

流化床颗粒包衣法制备替米沙坦氢氯噻嗪片

目的 采用流化床颗粒包衣法制备替米沙坦氢氯噻嗪片,并对其稳定性进行考察。方法 采用流化床一步造粒工艺制备替米沙坦颗粒,然后将替米沙坦颗粒进行不同包衣增重后与氢氯噻嗪以及合适的辅料混合,用普通旋转压片机进行压片制备替米沙坦氢氯噻片,并利用正交试验设计,优化替米沙坦氢氯噻嗪片处方;用HPLC进行含量和杂质检测,通过加速试验和长期试验考察片剂稳定性和溶出度。结果 该方法制备的替米沙坦氢氯噻嗪片质量稳定。羧甲基淀粉钠外加用量20.4 mg、氢氧化钠用量8.5 mg溶出指标最为理想,最终优化的处方与原研制剂溶出特征一致。结论 以流化床颗粒包衣法制备的替米沙坦氢氯噻嗪片质量稳定,工艺较双层片简单,具有可行性。     

灰色绝对关联度在盐酸普萘洛尔延迟缓释微丸处方优化中的应用

目的:探讨灰色绝对关联度在盐酸普萘洛尔延迟缓释微丸处方优化中的应用.方法:采用正交试验设计考察盐酸普萘洛尔延迟缓释微丸处方优化中的4个因素,以灰色绝对关联度为处方优化指标来优化处方.结果:最优处方为:内层致孔剂用量为12％,外层包衣增重为35％,外层包衣材料中Aquacoat ECD-30和Eduragit L30D-55配比为1∶1,内层包衣增重为10％、结论:根据最优处方制备的盐酸普萘洛尔延迟缓释微丸达到预期的体外释放,故灰色绝对关联度可作为缓控释制剂处方优化指标.