吲哚美辛肠溶片的含量测定

吲哚美辛肠溶片是消炎镇痛类药,临床上广泛应用于类风湿性关节炎的治疗。中国药典1995年版规定,测定吲哚美辛肠溶片的含量需去除肠溶衣后进行。实验中我们发现由于吲哚美辛片的片芯小、肠溶衣薄,包衣与片心粘连在一起,很难准确无误地去除包衣。基于此,我们对吲哚美辛肠溶片按药典的含量测定法进行了去除包衣与否的对比试验。     

不同厂家吲哚美辛肠溶片的体外溶出度比较

目的 探讨不同厂家吲哚美辛肠溶片的体外溶出度情况.方法 采用转篮法进行体外溶出度试验,紫外分光光度法检测溶出介质中药物浓度,计算累积释放量,以威布尔分布拟合溶出参数,并对溶出参数进行统计分析.结果 各药厂生产的吲哚美辛肠溶片在酸性介质(0.1 mol/L的盐酸)中的溶出度均符合规定.但不同厂家的吲哚美辛肠溶片溶出度参数有差异.结论 为保证药品的质量稳定性,相同剂型的同类制剂其生产工艺、原辅料质量等应有统一的标准.     

尼群地平片溶出度测定

目的采用不同方法考察市售尼群地平口服片剂和软胶囊的溶出度 ,并提出尼群地平溶出度检查的标准。方法用含不同浓度的十二烷基硫酸钠 (SDS)醋酸盐缓冲液 (pH 4 5 )为溶出介质 ,采用紫外分光光度法检查 ,比较不同厂家尼群地平片和尼群地平软胶囊的体外溶出度。用相似因子法对片剂溶出度数据进行统计分析。结果用 0 3 %SDS醋酸盐缓冲液 (pH 4 5 ) ,除B片和D片之间的 (B片 D片 )相似因子F2 >5 0外 ,其余的F2 ≤ 5 0 ,可以显示出不同厂家生产的尼群地平片的溶出度差异。而用 0 1 %SDS醋酸盐缓冲液可以显示出尼群地平软胶囊与片剂的溶出度差异。结论不同厂家生产的尼群地平片的溶出度存在较大的差异 ,尼群地平片和软胶囊在溶出度方面整体存在较大差异 ,建议《中华人民共和国药典》规定尼群地平片剂的溶出度检查     

吲哚美辛-泊洛沙姆188固体分散体的制备

目的制备吲哚美辛-泊洛沙姆188固体分散体,提高吲哚美辛的溶出度。方法以泊洛沙姆188为载体,采用溶剂-熔融法制备固体分散体。用差示热分析(DTA)、扫描电子显微镜(SEM)考察药物在载体中的存在状态,并进行体外溶出度研究。结果吲哚美辛以微晶或无定形分散在载体中,药物的溶出度随载体比例增加而增加。结论制备的固体分散体吲哚美辛的溶出度和溶出速率显著提高。     

国产乙基纤维素水分散体用于吲哚美辛缓释小丸的包衣工艺研究

目的：研究国产乙基纤维素水分散体包衣吲哚美辛缓释小丸的包衣工艺.方法：以国产乙基纤维素水分散体为包衣材料,添加癸二酸二丁酯为增塑剂,设计正交试验,在流化床中以不同操作条件制备吲哚美辛缓释小丸,考察小丸的药物释放度,并用电镜观察了小丸表面特征.结果：采用合适的流化床包衣工艺,采用国产乙基纤维素水分散体包衣能够制得和市售品（有机溶剂包衣）释放性能相似的吲哚美辛缓释小丸.结论：包衣工艺参数能够明显影响缓释小丸的药物释放度和表面特征.     

不除肠溶衣测定吲哚美辛肠溶片的含量

目的:研究肠溶衣对吲哚美辛肠溶片含量测定的影响。方法:采用紫外分光光度法,并进行配对设计的t检验。结果:肠溶衣溶液在 310～340 nm范围内无吸收。P>0.05(n=5)。差别无显著性意义。结论:肠溶衣对吲哚美辛肠溶片的含量测定无干扰,可不除肠溶衣进行该片的含量测定。     

肠溶衣对测定吲哚美辛肠溶片含量的影响

目的 探讨肠溶衣对吲哚美辛肠溶片含量测定的影响.方法 用紫外分光光度法检测肠溶衣对吲哚美辛含量测定的影响,结果用配对设计t检验.结果 肠溶衣溶液在波长310～340 nm范围内无吸收.去除肠溶衣与未去除肠溶衣含量测定无显著差别.结论 肠溶衣对吲哚美辛肠溶片含量测定无影响,可不去除肠溶衣进行含量测定.     

非诺贝特体外溶出度考察及其微粉化制剂的研究

目的考察不同厂家非诺贝特固体制剂体外溶出度以及微粉化对非诺贝特溶出度的影响。方法分别以 40 % (φ)乙醇溶液、5 0 % (φ)乙醇溶液、5g/L十二烷基硫酸钠溶液、1 0g/L十二烷基硫酸钠溶液为溶出介质 ,对 4种市售非诺贝特固体制剂的体外溶出度进行考察。采用球磨机制备微粉化非诺贝特 ,对其溶出度进行测定。结果 1 0 g/L十二烷基硫酸钠溶液中微粉化制剂的溶出速率明显快于其余 3种非微粉化制剂 ,初步探讨了非诺贝特固体制剂体外溶出度标准。用相似因子法对自制微粉化胶囊和法国生产的微粉化胶囊的溶出实验数据进行统计分析 ,结果表明两者溶出行为相似 ,相似因子f2 =72 4(5 0≤f2 ≤ 1 0 0 )。结论不同厂家非诺贝特固体制剂的溶出度差异较大 ,微粉化工艺能显著提高非诺贝特的溶出度     

呋喃妥因缓释微丸的人体内药物动力学研究

采用高效液相色谱法测定单剂量口服呋喃妥因缓释微丸 (NF PE)和市售肠溶包衣片(NF TA)后的尿药浓度 ,研究该药缓释微丸的药动学参数和生物利用度 ,并考察其体内外相关性 .结果表明 :呋喃妥因缓释微丸相对于肠溶包衣片的生物利度为 130 2 5 % ;供试品呋喃妥因缓释微丸和对照品肠溶包衣片的消除速率常数分别为 0 44 98h-1、0 82 0 2h-1,前者的消除半衰期(t1/ 2 )及平均滞留时间 (MRT)均较后者有所延长 ;该药体内吸收率与体外溶出度相关性显著 (r =0 972 4) .     

共聚维酮对交联聚维酮改善溶出度作用的影响

目的考察共聚维酮对交联聚维酮改善溶出度作用的影响。方法以头孢呋辛酯、阿苯达唑和吲哚美辛为模型药,采用直接压片工艺制备片剂,以溶出度为主要评价指标,考察交联聚维酮和共聚维酮用量对难溶性模型药物溶出度的影响。结果共聚维酮的加入,可以在超级崩解剂交联聚维酮用量不变甚至减少的情况下,较大的提高头孢呋辛酯和阿苯达唑的溶出度,而对吲哚美辛的溶出度无显著影响。结论共聚维酮可以显著增强交联聚维酮对某些药物溶出度的改善作用。     

羟丙基甲基纤维素酞酸酯假胶乳的制备及应用于消炎痛肠溶包衣片的质量评价

实验制备了肠溶辅料羟丙基甲基纤维素酞酸酯（ＨＰＭＣＰ）假胶乳水性分散液，并以消炎痛片为底物，分别采用ＨＰＭＣＰ假胶乳及ＨＰＭＣＰ有机溶媒包衣液制备其肠溶薄膜包衣片。考察并比较了两种包衣系统的消炎痛包衣片的崩解时限、抗胃液性能及在人工肠液中的释药动力学。实验结果表明：两种包衣系统均能使包衣片产生良好的肠溶性；包衣片在人工胃液中的药物泄漏率均符合ＵＳＰⅩⅫ要求；经统计学检验两种包衣系统的不同包衣水平间的体外累积释药Ｔｄ值，均无显著性差异（Ｐ＞０．５），说明在一定包衣增重范围内，衣膜对包衣片释药速度影响不大。     

Use of enteric polymers for production of microspheres by extrusion-spheronization

To simplify the manufacture of enteric dosage forms, incorporation of enteric polymers into the matrix of phenylbutazone microspheres produced by extrusion-spheronization was compared to the coating of cores. The effect of different polymers, cellulose acetate phthalate (CAP), hydroxypropylmethyl cellulose phthalate (HPMCP) and Eudragit L100-55 and the amount of granulating liquid were evaluated for the effect of selected physical properties and drug release behavior. Using the enteric polymers in the microsphere cores showed a similar pattern of release to the coated spheres with no notable difference in drug release behavior being observed between the dosage forms. The microspheres with Eudragit L100-55 in the matrix were less friable and disintegration times were much closer to the coated microspheres than formulations including the other polymers. Variation of the amount of Eudragit L100-55 in the cores allowed optimization of disintegration and drug release profiles.     

吲哚美辛肠溶片处方工艺对释放度的影响

通过对吲哚美辛肠溶片处方及工艺的改进，如添加适量乳糖和十二烷基硫酸钠及PVP、控制原药细度、修改包衣工艺等措施，解决了原产品存在的释放度低及其在贮存期间释放下降的问题，使吲哚美辛肠溶片释放工增加，稳定性提高。     

吲哚美辛肠溶滴丸的研制及其体外释药研究

研制吲哚关辛（IDM）肠溶滴丸,并考察其体外释药特性。方法：选用PEG6000为基质,用正交试验筛选IDM滴丸的最佳处方及工艺,并采用聚丙烯酸树脂Ⅱ为肠溶材料对其进行包衣,制备IDM肠溶滴丸。转篮法对其体外释药特性进行考察,并与市售IDM肠溶片进行比较。结果：筛选出IDM滴丸最佳制备条件为：IDM与总基质的质量比为1：3,滴速为65滴／min,滴制温度为90℃,冷凝液温度为5℃。IDM肠溶滴丸及市售IDM肠溶片在酸性介质中几乎不释药,而在pH为6.8的磷酸盐缓冲液中,IDM肠溶滴丸的释药速度显著高于市售肠溶片（P〈0．05）。结论：IDM肠溶滴丸具有明显肠溶效果,同时可加快IDM在肠道中的释放速度,值得进一步研究。     

Influence of water soluble additives and HPMCP on drug release from sureleaseê-coated pellets containing tamsulosin hydrochloride

The objective of this study was to investigate the influence of various water-soluble additives and HPMCP as an enteric polymer into Surelease for the developement of oral controlled release system containg tamsulosin hydrochloride. The drug loaded pellets were coated with only Surelease or Surelease containing HPMC, PEG 4000, mannitol and HPMCP (20% w/w). In case of HPMC and PEG 4000 as additives into Surelease film, the rapid drug release was observed in pH 1.2 while the higher drug release was achieved by adding HPMCP into Surelease as well as by increasing the amount of HPMCP (10, 20, and 30% w/w) in pH 7.2. The incorporation of HPMCP into Surelease showed pH-denpendent drug release due to its pH-dependent nature. Therefore, the incorporation of HPMCP into Surelease based on aqueous coating formulation is an effective way to develop oral controlled release delivery systems containing tamsulosin hydrochloride.     

Development of an enteric coating formulation and process for tablets primarily composed of a highly water-soluble, organic acid.

The purpose of this study was to define coating conditions for the enteric coating of a highly water soluble, acidic tablet core. Acidic tablet cores containing a marker drug were separated into three groups and seal coated to coverage levels of 0% (uncoated, white), 1% (yellow), and 3% (tan) weight gains. By employing a 'color coding' scheme, the different seal coated tablets could be coated simultaneously to reduce the number of experiments and eliminate potential differences that may exist during separate coating processes. In addition, an allotment of each coded tablet type was sequentially numbered with a marker pen, weighed, and recorded in order to identify the precise level of enteric coating as well as to monitor the variability of a given coating operation. The tablets were coated with five Eudragit((R)) L30D-based enteric formulations containing different amounts of plasticizer (10-20 parts) and talc (10-50 parts). During each enteric coating process, a predetermined amount of labeled tablets were removed after attaining 6, 8, and 10% weight gains. The labeled tablets were re-weighed, sorted, and then tested using USP disintegration and dissolution methods. Weight gain measurements of individual tablets indicated low coating variability (6.2% RSD) during the enteric coating processes. Dissolution results revealed that all enteric coat formulations inhibited drug release for 2 h in 0.1 N HCl. In contrast, it was found that tablets without a seal coat failed the USP disintegration test. In addition, seal coated tablets exhibited ca. 1.5-5 fold greater drug release at most intermediate sampling time points in phosphate buffer, pH 6.8, than tablets without a seal coat, suggesting that the dissolution of the latter was delayed by the generation of an acidic microenvironment at the interface of the enteric coat/acidic tablet core. Prior to enteric coating an acidic, highly water soluble substrate, a seal coat barrier should be applied to prevent retardation in drug release. A simple strategy utilizing color coding and tablet marking can be employed to test the effect of a seal coat, evaluate enteric coating formulations and process with minimal experimentation and analyses.     

4-氨基水杨酸钠结肠定位包衣片的制备及释放度测定

目的:以多层包衣法制备4-氨基水杨酸钠口服结肠定位系统,并考察其释放度,评价包衣工艺的稳定性。方法:用渗透型和肠溶型丙烯酸树脂依次包衣,制备pH、时间双重依赖的4-氨基水杨酸钠口服结肠定位包衣片;采用紫外分光光度法测定包衣片在不同pH条件下的释放度及3批包衣片在pH=7.4介质中的累积释放度,计算并比较释放参数T50、Td、T80、m。结果:包衣片在pH=6.5介质中12h释药量小于5%,有明显时滞;在pH=7.0、pH=7.4介质中12h内释药量均大于80%,无时滞效应;3批包衣片溶出度参数之间比较均无显著性差异(P>0.05)。结论:以渗透型和肠溶型丙烯酸树脂依次包衣制备的4-氨基水杨酸钠口服结肠定位包衣片具备理想的定位与缓释功能,包衣工艺稳定,重现性好。     

无时滞非达霉素肠溶片的制备及溶出评价

目的: 制备无时滞非达霉素肠溶片,考察其溶出特性。方法: 采用湿法制粒工艺,通过正交实验进行片芯优化,以甲基丙烯酸与丙烯酸乙酯共聚物为肠溶包衣材料,制备非达霉素肠溶片,以体外释放度为指标,考察其溶出行为。结果: 片芯中羟丙甲纤维素和交联羧甲基纤维素钠的用量分别为1.2%和4.5%,微晶纤维素和淀粉的比例为3:1,肠溶层共聚物的比例为50%时,制备的非达霉素肠溶片在pH1.0盐酸中2h释放度小于10%,在pH4.5醋酸盐缓冲液中可以崩解释放,在pH6.8磷酸盐缓冲液中快速释放,10min释放度大于60%。结论: 制备的非达霉素肠溶片与普通肠溶片相比无时滞效应,有望进行工业化生产。     

Compression of pellets coated with various aqueous polymer dispersions

Pellets coated with a new aqueous polyvinyl acetate dispersion, Kollicoat SR 30 D, could be compressed into tablets without rupture of the coating providing unchanged release profiles. In contrast, the compression of pellets coated with the ethylcellulose dispersion, Aquacoat ECD 30, resulted in rupture of the coating and an increase in drug release. Plasticizer-free Kollicoat SR coatings were too brittle and ruptured during compression. The addition of only 10% w/w triethyl citrate as plasticizer improved the flexibility of the films significantly and allowed compaction of the pellets. The drug release was almost independent of the compression force and the pellet content of the tablets. The inclusion of various tabletting excipients slightly affected the drug release, primarily because of a different disintegration rate of the tablets. The core size of the starting pellets had no influence on the drug release. Pellets coated with the enteric polymer dispersion Kollicoat 30 D MAE 30 DP [poly(methacrylic acid, ethyl acrylate) 1:1] lost their enteric properties after compression because of the brittle properties of this enteric polymer. Coating of pellets with a mixture of Kollicoat MAE 30 DP and Kollicoat EMM 30 D [poly(ethyl acrylate, methyl methacrylate) 2:1] at a ratio of 70/30 and compaction of the pellets resulted in sufficient enteric properties.     

盐酸帕罗西汀肠溶缓释片的制备及体外释放研究

目的制备盐酸帕罗西汀肠溶缓释片,并对其体外释放度进行考察。方法采用HPMC K100LV和HPMC K4M作为骨架材料,以水乳糖为填充剂制备盐酸帕罗西汀缓释片芯,再使用Eudragit L30D-55包肠溶衣,制成盐酸帕罗西汀肠溶缓释片,并采用f_2相似因子法评价自制制剂和参比制剂在释放介质中的体外释放行为。结果体外释放度实验显示,自制制剂和参比制剂的f_2相似因子值大于50。结论制备的盐酸帕罗西汀肠溶缓释片的释药行为与参比制剂的体外释放行为相似。