血塞通脉冲控释片的处方优化

目的:优化血塞通脉冲控释片的处方。方法:采用单因素试验考察片芯崩解剂种类、片芯崩解剂用量、包衣液组成和包衣增重百分率对药物累积释放率的影响;采用正交试验考察片芯崩解剂用量、包衣液组成、包衣增重百分率对释药时滞时间的影响,优化血塞通脉冲控释片的处方。结果:最佳处方为片芯崩解剂用量为15%,包衣增重百分率为9%,包衣液组成为Eudragit L100∶EC=1.5∶1(m/m);在该处方条件下,血塞通脉冲片的体外释药时滞为6 h左右,然后迅速脉冲式释药。结论:所选处方合理,制备的血塞通脉冲控释片能达到设计要求,体外试验可达到脉冲释药时滞效果。     

5-单硝酸异山梨酯脉冲控释片的家犬体内药动学

目的：考察5-单硝酸异山梨酯（IS-5-MN）脉冲控释片在家犬体内药动学特征及相对生物利用度。方法：采用随机化方法将家犬6条分成两组，以市售单硝酸异山梨酯片为对照制荆，交叉灌服自制IS-5-MN脉冲控释片和市售单硝酸异山梨酯片，采用气相色谱电子捕获法测定血药浓度，考察自制IS-5-MN脉冲控释片在体内的脉冲控释效果。结果：Ⅲ型（体外时滞为3h的脉冲片）IS-5-MN脉冲控释片在家犬体内的时滞为2．6h，市售IS-5-MN片的时滞为0．25h，而Cmax、AUC等两者无明显差异。结论：本研究制备的脉冲释放制剂为防治心血管疾病凌晨发作提供了一个良好的剂型选择，达到了设计要求。     

盐酸胺碘酮包衣脉冲片在犬体内的药动学研究

目的：建立测定盐酸胺碘酮包衣脉冲片在家犬体内血药浓度的方法,研究其药动学特征。方法：将家犬随机均分成盐酸胺碘酮包衣脉冲片组和普通片组,每日灌服200mg,1周后交叉实验,采用高效液相色谱法测定给药后24h内盐酸胺碘酮在2组家犬体内的血药浓度,并计算比较2组的药动学参数。色谱柱为Agilent C18,流动相为2%三乙胺（用磷酸调pH值至4.8）-乙腈（30：70）,柱温为25℃,检测波长为242nm。结果：盐酸胺碘酮检测浓度的线性范围为5～200μg·mL-1（r=0.9999）,提取回收率为91.62%～95.82%,RSD为1.83%～3.68%;盐酸胺碘酮在包衣脉冲片组和普通片组家犬体内的药动学参数分别为：t1/2为（17±1.68）、（18±2.16）h,tlag为（4.42±0.3）、（0.2±0.05）h,AUC0～24h为（298.4±32.5）、（278.4±24.8）μg·h·mL-1,cmax为（23.56±2.12）、（24.89±1.56）μg·mL-1,其中tlag有明显差异（P〈0.01）,而t1/2、cmax、AUC0～24h等无明显差异（P〉0.05）。结论：盐酸胺碘酮包衣脉冲片具有缓释作用,体内实验满足脉冲释药时滞效果。     

血塞通包衣脉冲控释片体外释药特性的研究

目的建立血塞通包衣脉冲片体外释放度测定方法,考察其体外释药特性。方法 RP-HPLC梯度洗脱法测定血塞通包衣脉冲控释片中的人参皂苷Rb1、人参皂苷Rg1、三七皂苷R1的含量;在模拟人胃肠溶出介质环境下,比较血塞通包衣脉冲控释片与普通片剂体外释药时滞和累积释药的脉冲效果。结果人参皂苷Rb1、人参皂苷Rg1在3.0⁶0μg,三七皂苷R1在0.860μg,三七皂苷R1在0.8¹6μg内与峰面积具有良好的线性关系,r值分别为0.999 8、0.999 4、0.999 6,低、中、高浓度平均回收率分别在99.0%16μg内与峰面积具有良好的线性关系,r值分别为0.999 8、0.999 4、0.999 6,低、中、高浓度平均回收率分别在99.0%⁹9.4%、99.1%99.4%、99.1%⁹9.3%、98.7%99.3%、98.7%⁹9.6%,RSD均<3.0%(n=3);体外释放度试验表明与血塞通普通片剂相比,血塞通包衣脉冲控释片释药时滞为5 h,体外累积释药>80%。结论血塞通包衣脉冲控释片在体外具有明显的脉冲释药特性,从而指导及优化处方作进一步研究。     

结肠定位释药双氯芬酸钠包衣片体内外相关性

目的研制时间依赖型口服结肠定位释药双氯芬酸钠包衣片。方法用释放度测定法研究双氯芬酸钠包衣片体外释放行为 ,用HPLC法测定包衣片在家犬体内的血药浓度 ,并计算出相关参数 ,进行体内外相关性考察。结果体外平均延迟释放时间为 4～ 5h时 ,体内平均时滞为 3～ 6h ,达到预期结果。结论本文研制的双氯芬酸钠片有进一步开发的价值     

盐酸胺碘酮包衣脉冲片的制备及体外释放度的研究

目的研制盐酸胺碘酮包衣脉冲片,并考查体外释放特性。方法以盐酸胺碘酮为模型药物,制备合适的片芯;以乙基纤维素和丙烯酸树脂L100的乙醇溶液包衣,滚转包衣技术制备盐酸胺碘酮脉冲释放片,采用正交实验优化其制剂工艺,并进行体外溶出度测定。结果片芯崩解剂的用量为8%,包衣增重量为12%,包衣组成Eud-ragit L100-EC=2∶1即能达到设计要求,按照优化后处方制备的脉冲片的体外释药时滞为(6.11±0.18)h。结论本脉冲片处方设计和工艺方法可行,体外试验满足脉冲释药时滞效果。     

盐酸维拉帕米脉冲释放片家犬体内的药动学及生物利用度

目的：比较盐酸维拉帕米脉冲释放片与其片芯在家犬体内的药动学特征及生物利用度。方法：采用拉丁方设计,将家犬6只随机分为2组,交叉口服Ⅳ型脉冲片和片芯,以片芯为对照制剂,考察体内脉冲效果。结果：Ⅳ型脉冲片在家犬体内的时滞为4h,而Cmax、AUC等无明显差异,达到设计要求。结论：本研究制备的脉冲释放制剂为防治心血管疾病的凌晨发作提供了一个良好的剂型选择。     

盐酸维拉帕米脉冲释放片体内外释药特性

目的：研究盐酸维拉帕米脉冲释放片体内外释药特性。方法：用干法压制包衣技术制备盐酸维拉帕米脉冲释放片，调整包衣中致孔剂用量，通过体外释放度试验考查时滞，并用HPLC法测定家兔血药浓度，考查体内外时滞的相关性。结果：体内外时滞基本相符。结论：可用体外时滞预测体内的时滞。     

盐酸曲马多控释片的制备及犬体内生物利用度研究

目的制备盐酸曲马多控释片,研究其在犬体内的相对生物利用度.方法以乙酸纤维素为包衣材料,以聚乙二醇400为致孔剂,制备每日给药2次的盐酸曲马多控释片;用HPLC法测定家犬单剂量交叉经口给药200 mg市售普通片和自制控释片后血浆中盐酸曲马多的浓度.结果犬体内普通片与控释片的AUC0～∞分别为(10 230.6±4-2 312.1)和(10 808.8±1 794.3)ng·h·mL-1;Cmax分别为(1 670.6±252.3)和(812.7±4-94.3)ng·mL;Tmax分别为(2.0±0.4)和(7.5±1.9)h.结论自制控释片在犬体内具有良好的控释效果,相对生物利用度为(107.0±8.2)%;体内外相关性良好.     

双氯芬酸钠脉冲控释微丸的研究

目的制备双氯芬酸钠脉冲控释微丸（DS-PRP）并考察体内外释药特性。方法采用水溶胀性材料为内包衣溶胀层，乙基纤维素水分散体为外包衣控释层制备DS-PRP，考察影响其体外释药的因素，并进行体内药代动力学研究。结果溶胀层材料类型、溶胀层和控释层包衣厚度、释放介质中十二烷基硫酸钠（SDS）的加入对DS-PRP的释药时滞和释药速率有显著影响，在0.1％ SDS溶液中释药时滞t_0.1为3.1 h，体内释药时滞tlag为2.8　h，与DS丸芯的相对生物利用度为（91±1２）%。结论DS-PRP在体内外均具有脉冲释药特性。     

醋氯芬酸缓释片和普通片体内外释药行为的相关性研究

目的对比研究醋氯芬酸缓释片和普通片的体外释放行为和Beagle犬体内的药动学,分析体内、体外释药行为的相关性。方法以紫外分光光度法测定两药的体外释放度,利用反相高效液相色谱法测定不同时间Beagle犬血浆中药物浓度,用DAS2.0统计软件计算有关药动学参数,Loo-Riegelman法计算体内吸收百分数,并对体内外相关性进行评价。结果醋氯芬酸缓释片体外恒速释放14h累积释放百分率在95%以上,普通片和缓释片的主要药动学参数达峰时间（tmax）为（2.833±1.169）h和（12.800±0.980）h,血浆半衰期（t1/2）为（2.650±0.261）h和（6.859±6.029）h,峰浓度（Cmax）为（23.457±8.881）μg/mL和（5.674±1.903）μg/mL,药时曲线下面积（AUC0-∞）为（113.171±16.529）μg.h/mL和（128.295±118.601）μg.h/mL,且体内外相关性较好。结论醋氯芬酸缓释片血药浓度平稳,与普通片相比可较长时间保持有效血药浓度。     

Pharmacokinetics and bioavailability of acyclovir sustained-release tablets in dogs.

The pharmacokinetics and bioavailability of acyclovir sustained-release tablets in dogs were investigated. Blood concentrations of acyclovir were determined by RP-HPLC after a single oral dose of two kinds of acyclovir tablets given separately to 6 beagle dogs. The main pharmacokinetics parameters of the acyclovir sustained-release tablet were as follows: T1/2, Tmax and Cmax were 4.10 +/- 0.20 h, 4.05 +/- 0.54 h and 6.90 +/- 0.68 [microg x ml(-1), respectively. MRT was 9.02 +/- 0.44 h. Using acyclovir standard tablet as control, relative bioavailability of the acyclovir sustained-release tablet was 152.2 +/- 49.90%. According to the two-tailed t-test, there was a distinct difference in the data for Tmax, Cmax and AUC between acyclovir sustained-release tablets and acyclovir standard tablets, and the absorbability of acyclovir sustained-release tablets was much better than that of the acyclovir standard tablets.     

Fast-disintegration oral tablets having sustained release property

Fast-disintegrating (FD) tablets containing nicorandil-loaded dry emulsions were prepared and their controlled-release properties were examined and compared with the plain FD tablets (FD tablets without dry emulsions) and commercial tablets. The dry emulsions were prepared with myristyl alcohol and stearyl alcohol and their property was modified by mixing the ratio of the two alcohols. Disintegration time of the prepared FD tablets was sufficiently fast (i.e., 12 to 23 s). In vitro release of nicorandil from the FD tablets containing the dry emulsions was sustained over 6 h, while that from plain FD and commercial tablets was complete within 5 min. In vivo absorption of nicorandil from the tablets was evaluated by oral administration in beagle dogs. FD tablets containing dry emulsions showed a similar AUC, lower Cmax, and delayed Tmax compared to the plain FD and commercial tablets. These results suggest that the dry emulsion-loaded FD tablets can be utilized to improve the sustained-release property of active drugs.     

尼可地尔口腔速溶片的研究

目的　制备尼可地尔口腔速溶片以提高其生物利用度和改善药物的苦味。方法　用croscarmellosesodium ,D-甘露醇和乳糖制备直径为6mm(崩解时限为12s)和10 mm(崩解时限为23s)的尼可地尔口腔速溶片。对其崩解性能、硬度、药物释放度、体内吸收及口感性能进行了考察。结果　压力在1.37×10⁸ Pa以上,甘露醇-乳糖比为9∶1,croscarmellosesodium的添加量为1% - 4%时,口腔速溶片的崩解时间较市售片缩短了1/3,且能达到一定的硬度。对Beagle犬经口服给药后,测得血药浓度与市售片相同,AUC ,C_max,T_max值无明显差异。口腔速溶片有长效和掩盖药物苦味的作用,同时甜味剂对掩盖药物苦味有相加作用。结论　口腔速溶片为快速崩解型片剂,与市售片等效,适合老龄和小儿患者服用     

诺氟沙星胃漂浮缓释片犬体内药动学及生物等效性研究

目的:研究诺氟沙星胃漂浮缓释片与普通片在犬体内的药动学特点及生物利用度。方法:将6只家犬随机分成2组,采用2种制剂双周期随机交叉自身对照实验设计方案,分别灌服400mg诺氟沙星胃漂浮缓释片(1片)或普通片(4片),于服药前和服药后0.5、1、2、3、4、6、8、10、13、16、24h分别取股静脉血,采用反相高效液相色谱法测定犬体内的血药浓度,用3p97药动学程序拟合,计算药动学参数并评价生物等效性。结果:诺氟沙星普通片和胃漂浮缓释片的Cmax分别为(3.51±0.57)、(2.51±0.55)μg.mL-1,tmax分别为(1.79±0.65)、(3.72±0.48)h,AUC0～24分别为(21.10±3.14)、(21.31±4.32)μg.h.mL-1,平均滞留时间分别为(5.68±0.51)、(7.71±0.67)h,胃漂浮缓释片相对生物利用度为103.5%。结论:诺氟沙星胃漂浮缓释片与普通片相比平均滞留时间延长,缓释效果更好,且2种制剂具有生物等效性。     

Factors affecting the absorption of nilvadipine from disintegration-controlled matrix tablet in dogs

The purpose of this study was to investigate the pharmacokinetics of nilvadipine (NiD) from disintegration-controlled matrix tablets (DCMT). A further purpose was to clarify biological factors that affect the absorption of NiD from DCMT. Two DCMT formulations, which released approximately 80% of NiD in 6 h (DCMT-M) and 10 h (DCMT-S) in vitro, were prepared and compared with immediate-release (IR) tablets. The T(max) and mean residence time from DCMT-M and DCMT-S were significantly longer than those from IR tablets in fasted dogs. The area under the plasma concentration-time curve (AUC) (0-infinity) from DCMT-M in both fed and fasted dogs and IR tablets were comparable in both fed and fasted dogs, indicating complete drug release and absorption without food effect. In contrast, the AUC from DCMT-S was significantly lower than the AUC from IR tablets in fasted dogs. The AUC from DCMT-S increased in fed dogs, but it was still lower than the AUC from IR tablets. In vivo absorption profiles calculated by deconvolution method suggested that the duration of drug absorption from DCMT-S was prolonged from 6 h in fasted condition to 8 h in fed condition, suggesting longer gastro-intestinal (GI) transit time in fed condition allowed longer drug release duration from DCMT-S. Regional drug absorption was also evaluated using NiD solution. The results indicated NiD was almost completely absorbed from canine jejunum, ileum and colon, indicating drug permeation is not a rate-limiting factor of NiD absorption. Therefore, limited GI transit time is the primary factor that affects the drug release from DCMT and subsequent NiD absorption.     

头孢丙烯分散片在Beagle犬体内的药动学和相对生物利用度研究

目的建立高效液相色谱（HPLC）法测定犬血浆中头孢丙烯的质量浓度,研究头孢丙烯分散片在Beagle犬体内的药动学和相对生物利用度。方法 12只Beagle犬双周期随机交叉单剂量口服500mg头孢丙烯分散片和普通片剂,洗净期为1周,采用HPLC法测定血浆中头孢丙烯的质量浓度。结果分散片与普通片的体内过程基本一致,其主要药代动力学参数峰浓度（Cmax）分别为（48.7±4.2）μg/mL和（51.1±3.3）μg/mL,达峰时间（Tmax）分别为（1.5±0.3）h和（2.0±0.4）h,半衰期（t1/2）分别为（1.2±0.3）h和（1.6±0.4）h,0～24h药-时曲线下面积（AUC0-24）分别为（188.9±27.5）μg/（h·mL）和（208.2±34.3）μg/（h·mL）。结论头孢丙烯分散片口服后吸收迅速,平均相对生物利用度为90.7%。     

替硝唑果胶骨架型结肠定位缓释片在犬体内药动学研究

目的 研究替硝唑果胶骨架型结肠定位缓释片在犬体内药动学.方法 采用双周期交叉试验设计,6只健康Beagle犬分别服用受试制剂或参比制剂,用HPLC法测定Beagle犬血浆中药物浓度.结果 受试、参比制剂在犬体内的血药浓度变化符合二室模型,其主要药动学参数：Tmax分别为（7.0±0.92）和（2.0±0.31）h;Cmax分别为（66.97±5.9）和（112.2±7.4）μg/L;AUC0-t分别为（1243.88±25.67）和（1523.84±27.89）mg·h/L;AUC0-∞分别为（1277.18±30.58）和（1548.67±20.89）mg·h/L,受试制剂的相对生物利用度为82.47%.结论 本法准确、灵敏,适用于替硝唑果胶骨架型结肠定位缓释片的药动学研究.