尼群地平缓释胶囊在家犬体内的药动学与相对生物利用度

目的研究尼群地平缓释胶囊在家犬体内的药代动力学与相对生物利用度。方法用高效液相色谱法测定了 6条健康家犬口服尼群地平缓释胶囊 (受试制剂 )和尼群地平普通片 (参比制剂 )后不同时间点血浆中尼群地平的浓度 ,绘制血药浓度 -时间曲线 ,计算药代动力学参数及相对生物利用度。结果受试犬口服含尼群地平 4 0mg的受试制剂和参比制剂后 ,血浆中尼群地平的tmax分别为 (6 1 7± 1 60 )和 (1 4 6± 0 5 1 )h;cmax分别为 (3 4 3 8± 1 2 2 6)和 (45 6 5± 1 0 7 4 )nmol L ;用梯形法计算 ,AUC0～t分别为 (1 93 0 1± 1 0 0 5 1 0 6)和 (1 790 8± 94 2 8)nmol·h L。以AUC计算 ,与参比制剂相比 ,受试制剂中尼群地平的相对生物利用度平均为 (1 1 0 5 9± 2 3 60 ) %。将AUC0～t经对数转换后进行方差分析 ,结果表明 ,受试制剂与参比制剂相比 ,除个体间外 ,周期间与制剂间无显著性差异 (P >0 0 5 ) ,受试制剂AUC0～t的 90 %置信区间为参比制剂的 88 5 4 %～ 1 3 1 93 %。结论尼群地平缓释胶囊与国外普通片相比 ,在犬体内具有更长的作用时间 ,且相对生物利用度相近     

气固顶空色谱法测定植入用缓释氟尿嘧啶中环己烷

目的:测定植入用缓释氟尿嘧啶中环已烧残留量。方法:研碎供试品,置针管中于60℃保温作气固顶空平衡,顶空气以气相色谱法测定,氢焰检测器,SE-30固定相,柱温80℃。结果:方法的精密度RSD为2.8％,回收率为101.4％,10～110ng·mL~(-1)范围内线性良好,检出限为3.4ng·mL~(-1)。结论:为类似难溶性固体药物的有机溶剂残留量检测提供了可靠的方法。     

Drug release from reservoir pellets compacted with some excipients of different physical properties

The aim of the present study was to investigate the influence of the size and the porosity of excipient microcrystalline cellulose (MCC) particles on the densification and the deformation during compaction and the consequent effect on the drug release from reservoir pellets. Drug pellets consisting of salicylic acid and microcrystalline cellulose were prepared by extrusion-spheronisation and spray-coated with ethyl cellulose (ethanol solution). Excipient pellets of different size and porosity were prepared by extrusion-spheronisation or direct spheronisation. Five binary mixtures of reservoir pellets and excipient particles were prepared in the proportion 1:7 and lubricated. After compaction the reservoir pellets were retrieved and analysed to determine the intragranular porosity, surface area, shape and drug release. The reservoir pellets were shown to undergo extensive deformation and densification during compaction, resulting in a preserved or even prolonged drug release time. The mode of deformation of the reservoir pellets seems to be critical for the compression-induced change in drug release. Formation of large indents has a negative effect on the release time, while the use of small particles or small deformable agglomerates has a protective effect. We also hypothesize that the coating structure changes during compaction and the final structure of the coating is the net effect of two parallel processes, one reducing and one prolonging the drug transport time across the coating.     

Effect of intragranular porosity on compression behaviour of and drug release from reservoir pellets

In this study, reservoir pellets were prepared and their compression behaviour as well as the importance of their porosity for compression-induced changes in drug release was investigated. Pellets of three different porosities, consisting of microcrystalline cellulose and salicylic acid, were prepared by extrusion–spheronisation and spray-coated with ethyl cellulose (ethanol solution). Lubricated reservoir pellets were compressed and retrieved by deaggregation of the tablets. The retrieved pellets were analysed regarding porosity, thickness, surface area, shape and drug release. It was found that the coating did not significantly affect their compression behaviour. Compaction of pellets of high original porosity considerably affected densification and degree of deformation, whereas the effect on drug release was minor. For low porosity pellets the influence of compaction on drug release was appreciable, but only slight regarding densification and degree of deformation. In conclusion, the porosity of pellets is a potential factor that the formulator can use to optimize drug release and one that can affect the robustness of a formulation during manufacture. Moreover, the coating may be able to adapt to the densification and deformation of the pellets.     

氧化苦参碱胃内滞留缓释片的研制

目的：为延长苦参素的作用时间，降低肠道菌群的降解作用，便于给药，制成苦参素胃内滞留缓释片。方法：以HPMC为骨架材料，十六醇为助漂剂，碱式碳酸镁为产气剂，制备了一天给药两次的胃内滞留型缓释片，并进行体外累积释放度测定。结果：体外释药符合Higuchi方程，r=0．9864，体外释药量与释药时间具有良好的相关性，3个取样点及累积释放百分率分别为：1h20％。45％、2h35％～60％、8h75％以上，且起漂时间不超过5min。结论：该缓释片处方工艺简单，适合工业化生产；缓释效果明显。     

盐酸恩丹西酮包芯缓释片的研制

目的　研制盐酸恩丹西酮包芯缓释片。方法　采用HPMC为骨质材料,通过正交设计试验优选最佳处方和工艺,考察释放介质pH值对缓释片释药特性的影响。结果及结论　释放介质pH值对盐酸恩丹西酮包芯缓释片释药影响较大,在酸性介质及中性蒸馏水中 2 4h释药完全(≥ 95 %),在 pH6 8磷酸盐缓冲液中释药不完全( <4 5 % ),0～ 14h体外释放符合零级动力学过程。     

洛伐烟酸双层缓释片的制备及释放度考察

目的分别采用进口与国产羟丙基甲基纤维素 (HPMC)作为骨架材料制备洛伐烟酸缓释双层片 ,并比较国内外HPMC的缓释作用。方法用紫外分光光度法测定该制剂缓释层中烟酸的释放度 ,并用相似因子法和Chow′s法对溶出试验数据进行统计分析。结果使用国产HPMC制得的缓释片及进口HPMC制得的缓释片与国外市售片Niaspan的释放行为完全相似 ,相似因子分别为F2 =87 6和F2 =89 2 (5 0≤F2 ≤ 10 0 )。结论缓释片处方设计合理 ,工艺简单 ,用国产HPMC代替进口HPMC作为凝胶骨架材料完全可行     

西替伪麻缓释片制备工艺及体外释药研究

目的：探讨西替伪麻缓释片的制备工艺及体外释药特性。方法：筛选最佳处方，采用湿法制粒，并制备双层西替伪麻缓释片。建立释放度检测方法，以HPLC法测定盐酸西替利嗪与盐酸伪麻黄碱含量，采用不同方程拟合自制片释放曲线，根据相似因子法计算并比较自制片与进口片的释药行为。结果：用25％HPMC K4M制得缓释片，其释药曲线可用一级方程动力学拟合，相似因子法算得f2为73．64，表明自制片与国外进口片的释药行为相似。结论：HPMC用量为25％时所制西替伪麻缓释片具良好的释药效果。     

复方双嘧达莫缓释片含量及有关物质水杨酸的测定

目的建立复方双嘧达莫缓释片双嘧达莫和阿司匹林含量及有关物质水杨酸的测定方法。方法采用反相高效液相色谱法测定片剂中双嘧达莫和阿司匹林的含量和有关物质游离水杨酸的限量。结果平均回收率为双嘧达莫100.1%,RSD为1.01%;阿司匹林99.13%,RSD为1.26%。水杨酸最低检测限为0.0025mg。结论测定方法可用于控制复方双嘧达莫缓释片的质量。     

苯扎贝特缓释微丸胶囊的研制及体内外评价

目的:研制苯扎贝特缓释微丸胶囊。方法:采用离心造粒技术制备苯扎贝特缓释微丸胶囊;以体外释药和犬的药代动力学参数进行评价。结果:微丸得率86.5%,载药量87.8%;体外释放曲线符合一级方程,相似因子f2为74.23;自制缓释微丸胶囊单剂量犬口服给药后的tmax(3.7±0.5)h,cmax(36.36±0.98)μg/mL,AUC0-∞(337.83±7.29)μg.h/mL;苯扎贝特缓释片(参比片)的tmax(4.1±0.4)h,cmax(39.66±0.94)μg/mL,AUC0-∞(327.27±8.97)μg.h/mL。结论:以进口的缓释片为参比片,自制的苯扎贝特缓释微丸胶囊具有良好的缓释作用;相对生物利用度为(103.3±2.8)%,两种制剂生物等效。