SM-1小粒径肠溶微丸的制备及体外评价

目的制备SM-1小粒径肠溶微丸,并优化其处方,以达到肠溶和便于小动物给药的目的。方法采用流化床空白丸芯上药法,在丸芯表面依次包覆含药层、羟丙基甲纤维素（HPMC）隔离层和丙烯酸树脂（EudragitL30D-55）肠溶层。以载药量、耐酸性及释放度为指标,对SM-1肠溶微丸的处方进行优化。结果隔离层增重8%,肠溶层增重15%的肠溶微丸粒径〈450μm（40目筛）,圆整度良好,载药量约为20%;在pH为2.0的盐酸溶液中2 h内肠溶衣层薄层完好,药物释放度〈4%;在pH为6.8的PBS溶液中,45 min内释放度均〉70%。结论采用流化床制备SM-1肠溶微丸工艺可行,重现性好,具有良好的肠溶特性,粒径〈380μm,可用于小动物给药。     

盐酸氟西汀肠溶片的研制

采用单因素法筛选了盐酸氟西汀肠溶片片芯、隔离层包衣液和肠溶衣包衣液的处方.结果表明,片芯中的关键辅料羟丙甲纤维素E50、羧甲淀粉钠和微晶纤维素的用量分别为5％、15％和25％,黏合剂宜采用5％淀粉浆.以5％欧巴代Y-1-7000水分散体对所得片芯包隔离衣层,增重为1％,再以5％聚丙烯酸树脂L30D-55(含5％单硬脂酸甘油酯和1％甘露醇)包肠溶衣层,增重为3％.所得制品在0.1 mol/L盐酸中2h累积释放率≤5％,在pH 6.8缓冲液中30 min释放完全.3批制品的体外释放曲线均与参比制剂(ProzacWeekly胶囊)相似,相似因子(f2)均大于50.     

盐酸维拉帕米脉冲控释片的制备及体外释放度研究

制备了渗透泵控释的盐酸维拉帕米片芯，依次包时滞衣层和控释衣层制得脉冲控释片。考察了时滞衣层增重和控释衣膜处方及增重对药物释放时滞和释放速率的影响，同时比较了制品在不同释放介质中的释药行为。结果显示，时滞衣层增重与脉冲控释片的释放时滞呈正相关（r=0．9959），但对药物的释放速率影响较小；控释衣膜中的致孔剂种类和用量及控释衣层增重对体外释药均有不同程度的影响；释药孔的数量对药物释放影响较小，但释药孔的减少可能会导致衣膜膨胀变形。脉冲控释片的体外释放不受介质pH的影响。     

尼群地平口服定时释药片的成型工艺考察

目的：研究尼群地平口服定时释药片的成型工艺。方法：以崩解时间为指标筛选片芯处方、工艺。应用薄膜包衣技术，采用羟丙基甲基纤维素（HPMC）为成膜材料，巴西棕榈蜡和蜂蜡混合物为阻滞剂制备尼群地平口服定时释药片，并考察巴西棕榈蜡和蜂蜡混合物用量、比例、片芯增重量、不同pH溶出介质和转篮转速对定时释药的影响。结果：经过筛选确定片芯处方为每片含尼群地平10mg，微晶纤维素（MCC）81mg，低取代羟丙基纤维素（L-HPC）9mg，硬脂酸镁0．5％；包衣混悬液处方为5％HPMC，3．5％巴西棕榈蜡，1．5％蜂蜡，0．5%PEG4000，0．5％吐温-80，89％水。结论：巴西棕榈蜡和蜂蜡混合物用量与比例，包衣层厚度，是影响定时释药的主要因素。巴西棕榈蜡和蜂蜡混合物用量越多，释药时滞越长；混合物总量不变，蜂蜡用量增大，释药时滞变长；包衣层厚度越厚，释药时滞变长。     

纳米碳酸钙肠溶生物黏附片的制备工艺研究

目的：研究纳米碳酸钙肠溶生物黏附片(NCaEBT)的制备工艺。方法：片芯处方筛选以HPMC K4M和CP 940的用量为考察因素,以Ca2+在1,4 h的累积释放度和黏附力为指标,采用星点设计-效应面优化法,确定片芯优化处方;对优化处方下制备的NCaEBT片芯以丙烯酸树脂Eudragit L100-55为肠溶液进行肠溶包衣,考察肠溶衣增重对NCaEBT的影响。结果：片芯处方筛选时以多元线性方程拟合的效果为佳,且具有较高的可信度,优化处方为片芯中HPMC K4M和CP 940的含量分别为15和27.5 mg,肠溶衣增重为片芯的10%。结论：本课题研制的NCaEBT体外试验能够实现肠定位、生物黏附和缓慢释放的特征,可用于开发成为驱铅治疗药物。     

扎托布洛芬缓释微丸的制备及释放特性

目的 以不同处方制备扎托布洛芬缓释微丸,考察包衣层处方对药物释放的影响及其释药特性.方法 采用空白丸芯流化床混悬液上药法制备扎托布洛芬载药微丸,以HPMC为隔离材料包隔离衣、以乙基纤维素水分散体为缓释材料,考察不同种类、用量的致孔剂以及包衣增重对药物释放行为的影响.结果 以10％ HPMC为致孔剂、缓释衣层包衣增重为4.5％时,制得的微丸具明显的缓释效果,其释放曲线符合一级动力学,且批内及批间重复性良好.结论 制得的扎托布洛芬缓释微丸具有较理想的体外缓释效果.     

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。     

丹皮酚结肠靶向片的大鼠结肠靶向性评价

目的:研究丹皮酚结肠靶向片剂在大鼠体内定位释药性能。方法:特制适合大鼠口服给药的3mm结肠定位包衣小片,通过相似性因子2评价包衣小片和包衣大片释放曲线的相似性,以小片代替大片进行体内释放评价,考察结肠靶向包衣片剂在大鼠胃、肠道中的释放性能。结果:特制包衣小片的隔离层、时滞层、肠溶层分别增重1.6%、7.3%、9.7%时,释放曲线与包衣大片大致相同,2为53,丹皮酚结肠靶向片75%的药物释放在小肠后端、盲肠以及结肠段,胃及小肠前、中段仅有少量释放。结论:丹皮酚结肠靶向片剂基本达到了结肠定位释药的效果。     

氢溴酸高乌甲素脉冲释放片的研究*

目的以氢溴酸高乌甲素为模型药物研究脉冲释放片剂并同时考察用包衣的方法制备脉冲给药系统的可行性.方法以氢溴酸高乌甲素为模型药物,制备适宜的片芯;以乙基纤维素和丙烯酸树脂Ⅱ号的乙醇溶液包衣,采用滚转包衣法,制备氢溴酸高乌甲素脉冲释放片剂.通过体外释放度实验,考察片芯和衣层对片剂释药行为的影响.结果片芯处方、包衣层厚度及包衣处方对氢溴酸高乌甲素脉冲释放片的释药行为均有影响.结论通过调整片芯中崩解剂的用量、包衣层的厚度和组成,可以得到具有不同释药时滞的氢溴酸高乌甲素片剂.     

雷贝拉唑钠肠溶片制备及其溶出度测定简

目的 制备雷贝拉唑钠肠溶片.方法采用处方筛选对其片芯各组分组成,隔离衣、肠溶衣处方及包衣增重进行了考察,并采用溶出度测定确定处方.结果 所优选的处方具有肠溶功能.结论 片芯中羟丙基纤维素、低取代纤维素是其主要影响因素,肠溶衣包衣增重为12%或18%时药物具有较好的抗酸力,可达到肠道给药的目的,但随着肠溶衣包衣增重的增加药物释放有减缓的趋势.     

硝苯地平缓释片释放度研究

目的建立硝苯地平缓释片的释放度试验方法，对5个厂家生产的硝苯地平缓释片的含量和释放度进行测定。方法以0．5％吐温-80水溶液（900mL）作为溶出介质，采用桨法测定溶出度，转速为100r／min，温度为（37．0±0．5）℃；用反相高效液相色谱法测定含量，测定波长为333nm。结果用建立的方法可以准确地测定各厂家硝苯地平缓释片的释放度，不同厂家生产的硝苯地平缓释片释放速度差别较大。结论对不同厂家生产的硝苯地平缓释片释放度进行检查，有助于控制产品质量。     

依托度酸缓释片释放度研究

依托度酸缓释片以ｐＨ７．５磷酸盐缓冲液（ＵＳＰ２３版）为释放介质,采用桨法,转速１００ｒ／ｍｉｎ进行释放度测定。紫外分光光度法以２７８为检测波长,本法线性关系良好。     

琥乙红霉素缓释片释放度研究

目的建立琥乙红霉素缓释片体外释放研究分析的硫酸显色法。方法以900 mL经脱气处理的0.1 mol/L盐酸溶液为释放介质,转速为75 r/min,75%的硫酸溶液为显色剂,采用紫外-可见分光光度法于482 nm波长处对琥乙红霉素缓释片的释放度进行测定。结果琥乙红霉素显色后质量浓度在40～72μg/mL范围内与吸收度呈良好线性关系(r=0.999 9);平均回收率为99.75%,RSD为0.76%;12 h内3批样品的释放量均在标示量的90%以上。结论该方法操作简便、准确可靠,可用于琥乙红霉素缓释片释放度的测定,为质量标准的制订提供了依据。     

盐酸安非他酮缓释片的含量测定及释放度研究

目的 建立盐酸安非他酮缓释片的含量测定方法并测定其释放度。方法 采用紫外-可见分光光度法测定盐酸安非他酮缓释片的含量及释放度,测定波长为251 nm。结果 线性范围在4.895～16.316μg·ml^-1,r=0.9999;盐酸安非他酮缓释片的平均回收率为99.4%,RSD为0.69%。结论 本法简便、准确、结果满意。     

法莫替丁生物黏附缓释片释放机制研究

目的探讨法莫替丁生物黏附缓释片的释药机制及影响因素。方法以羟丙基甲基纤维素（HPMC）为骨架材料，卡波姆为生物黏附材料，乳糖为辅料制备生物黏附缓释片，运用Ritger-Peppas方程释放指数n值，评价HPMC、卡波姆和乳糖对释药速率的影响。结果生物黏附片的释药速率随HPMC、卡波姆含量增高而减慢，乳糖可以加快释药速率，经处方筛选优化后制备的法莫替丁生物黏附缓释片的释放，是Fick扩散和凝胶骨架溶蚀两种机制的协同作用结果。结论HPMC、卡波姆和乳糖均可影响法莫替丁生物黏附片中主药的释放，生物黏附缓释片的释药过程可用Ritger—Peppas方程进行描述。     

盐酸安非他酮缓释片的含量测定及释放度研究

目的建立盐酸安非他酮缓释片的含量测定方法并测定其释放度。方法采用紫外-可见分光光度法测定盐酸安非他酮缓释片的含量及释放度,测定波长为251 nm。结果线性范围在4.895~16.316μg.ml-1,r=0.9999;盐酸安非他酮缓释片的平均回收率为99.4%,RSD为0.69%。结论本法简便、准确、结果满意。     

Clinical Evaluation of Modified Release and Immediate Release Tacrolimus Formulations

The science of drug delivery has evolved considerably and has led to the development of multiple sustained release formulations. Each of these formulations can present particular challenges in terms of clinical evaluation and necessitate careful study to identify their optimal use in practice. Tacrolimus is an immunosuppressive agent that is widely used in organ transplant recipients. However, it is poorly soluble, has an unpredictable pharmacokinetic profile subject to important genetic polymorphisms and drug-drug interactions, and has a narrow therapeutic index. For these reasons, it represents an agent that could benefit from modified release formulations to overcome these limitations. The objective of this review is to discuss the clinical evaluation of immediate and modified release tacrolimus formulations in renal transplant recipients. Clinical trials from early development of immediate release tacrolimus to formulation-specific post-marketing trials of modified release tacrolimus formulations are reviewed with an emphasis on key elements relating to trial design end endpoint assessment. Particular elements that can be addressed with formulation alterations, such as pharmacokinetics, pharmacogenomics, and toxicity and corresponding clinical evaluations are discussed. In addition, current knowledge gaps in the clinical evaluation of immediate and modified release tacrolimus formulations are discussed to highlight potential avenues for the future development of different tacrolimus formulations with outcomes relevant to the regulators, the transplant community, and to transplant recipients. This review shows that new formulations may alter tacrolimus bioavailability, alleviate certain adverse events while potentially enhancing patient convenience.     

卡托普利缓释制剂的释放研究

本文采用紫外分光光度法研究了卡托普利骨架片和微丸的释放过程，结果表明骨架片的体外释放符合Higuchi方程，而微丸符合零级动力学，并分别求得了释放速度方程及释放参数。两者均达到了显著的缓释效果。     

Pharmacokinetics of Coadministration of Guanfacine Extended Release and Methylphenidate Extended Release

Background

α₂-Adrenoceptor agonists are used adjunctively to psychostimulants in treating attention-deficit/hyperactivity disorder (ADHD) when psychostimulants alone do not sufficiently reduce symptoms. However, data on the pharmacokinetic profiles and safety of combination treatments in ADHD are needed.

Objective

The primary objective of this study was to evaluate the pharmacokinetic profiles of guanfacine extended release (GXR) and methylphenidate hydrochloride (MPH) extended release, alone and in combination.

Study Design

This was an open-label, randomized, three-period crossover, drug–drug interaction study.

Setting

The study was conducted at a single clinical research center.

Participants

Thirty-eight healthy adults were randomized in this study.

Interventions

Subjects were administered single oral doses of GXR (Intuniv^®; Shire Development LLC, Wayne, PA, USA) 4 mg, MPH (Concerta^®; McNeil Pediatrics, Titusville, NJ, USA) 36 mg, or GXR and MPH combined.

Main Outcome Measures

Guanfacine, dexmethylphenidate (d-MPH), and l-methylphenidate (l-MPH) levels were measured with blood samples collected predose and up to 72 h postdose. Safety evaluations included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms (ECGs).

Results

Thirty-five subjects completed the study. Analyses of the 90 % confidence intervals (CIs) for the geometric mean ratios of the maximum plasma concentration (C_max) and area under the concentration–time curve extrapolated to infinity (AUC_∞) values for guanfacine and d-MPH following administration of GXR or MPH alone or combined met strict bioequivalence criteria (90 % CIs within the interval of 0.80–1.25). Overall, combining GXR and MPH did not alter the pharmacokinetic parameters of either medication. Sixteen subjects (42.1 %) had at least one TEAE. The most commonly reported TEAEs included headache and dizziness following GXR, MPH, and GXR and MPH combined. Two subjects had clinically significant abnormalities in ECG results following coadministration: both events were mild and resolved the same day.

Conclusions

In this short-term, open-label study of healthy adults, coadministration of GXR and MPH did not result in significant pharmacokinetic drug–drug interactions. No unique TEAEs were observed with coadministration of GXR and MPH compared with either treatment alone.