处方和工艺因素对氨茶碱魔芋胶骨架片体外释放度的影响

目的：考察处方和工艺因素对魔芋胶骨架片体外释放度的影响，评价魔芋胶作为新型载体材料用于缓释骨架片制备的可行性。方法：以氨茶碱为模型药物，采用粉末直接压片法和湿法制粒压片法制备魔芋胶骨架片，考察魔芋胶粒度、黏度和用量，填充剂种类，主药粒度，压片工艺，压片压力等对其体外药物释放的影响。结果：氨茶碱魔芋胶骨架片可缓慢释放药物；随魔芋胶粒度降低，骨架材料用量或主药粒度增加，药物释放减慢；与淀粉、微晶纤维素和乳糖相比，Eudragit L100作为填充剂，可明显延缓药物释放；压片工艺，压片压力和魔芋胶黏度对药物释放影响不大。结论：魔芋胶可作为一种新型载体材料用于缓释骨架片的制备，魔芋胶粒度、用量，主药粒度和填充剂种类是影响骨架片体外药物释放的主要因素。     

氨茶碱魔芋胶骨架片的释药机制研究

目的研究氨茶碱魔芋胶骨架片的体外释药机制。方法以氨茶碱为模型药物,采用粉末直接压片法制备氨茶碱魔芋胶骨架片,测定不同搅拌转速条件下骨架片的体外溶蚀度与释放度,分别采用零级方程和Peppas方程对释药过程中骨架片的溶蚀度和释放度数据进行处理。结果骨架片的溶蚀符合零级方程,溶蚀量随搅拌转速增加而增加;骨架片的药物释放为扩散和溶蚀协同作用,随搅拌转速增加或释药时间延长,骨架片释药过程中扩散释放所占比例下降,溶蚀释放所占比例增加。结论氨茶碱魔芋胶骨架片的释药机制为非Fick扩散,即药物扩散和骨架溶蚀协同作用。     

银杏叶提取物缓释片的制备

目的:探讨银杏叶缓释片的制备处方,并对其体外释放度进行评价。方法:以体外累积释放度为指标,通过单因素考察找出影响释放的主要因素,再采用正交设计筛选出最佳处方。结果:通过正交设计及体外释放度考察,得到制备银杏叶缓释片的最佳处方为主药55%,HPMC30%,EC10%,乳糖5%,硬脂酸镁0.5%。体外释药的规律符合Ritger-Peppas动力学模型。结论:粉末直接压片法制得银杏叶缓释片,体外释放度实验表明释药具有较好的缓释特性。     

复方葡萄籽原花青素亲水凝胶骨架片的制备工艺及其释放度的研究

目的:研究复方葡萄籽花青素骨架片的处方工艺及其体外释药行为。方法:通过单因素试验,确定影响释药效果的主要因素,进行正交设计,以原花青素中单体成分儿茶素体外累积释放度为依据,优选出最佳工艺。结果:所制缓释片无突释现象,缓释周期12 h。采用零级、一级、Higuchi及Peppas方程判断儿茶素的释药机制,表明儿茶素释放行为符合Higuchi模型,释放机制为骨架溶蚀机制。结论:该法制备的复方葡萄籽花青素骨架片制备工艺简单易行,具有良好的释放机制。     

阿魏酸钠胃漂浮缓释片的制备及体外释放

目的:制备阿魏酸钠胃漂浮片,评价其体外释药性能。方法:以羟丙基甲基纤维素(HPMC)为亲水性凝胶骨架,碳酸氢钠为起泡剂,采用粉末直接压片方法制备漂浮片,以释放度、漂浮性能以及外观作为考察指标,进行处方筛选,并考察了制备方法和HPMC规格对体外释药的影响。结果:优化处方持漂时间达8 h,8 h体外累积释放度达到62%,显著高于市售普通片体外释放度的49%。结论:优化处方的阿魏酸钠胃漂浮片具有起漂时间快、缓释效果明显的特点。     

去甲斑蝥素缓释片的处方优化及其体外释药特性研究

目的:优化去甲斑蝥素缓释片制备处方及考察其释药特性。方法:以羟丙基甲基纤维素(HPMC)为骨架材料制备去甲斑蝥素亲水凝胶缓释骨架片;以HPMC用量(A)、乳糖用量(B)、乙醇浓度(C)、乙醇用量(D)为因素,以体外释放度综合评分值为指标筛选缓释片的最佳处方并考察其累积释药率。结果:缓释片的最佳处方为A12g、B1.5g、C90%、D10mL;所制缓释片2、6、12h的累积释药率分别为(30.63±1.03)%、(51.70±1.51)%、(89.25±1.04)%,药物释放机制为扩散和骨架溶蚀的协同作用。结论:优化处方制备的去甲斑蝥素缓释片可以达到预期缓释效果。     

4-氨基吡啶凝胶骨架缓释片的制备及体外释放

目的:制备4-氨基吡啶(4-aminopyridine,4-AP)亲水凝胶骨架缓释片。方法:以羟丙甲纤维素的规格、处方用量及乳糖处方用量为因素设计正交试验,以体外释放度为考察指标,优化4-AP凝胶骨架片的处方,并进行批内和批间体外释放度验证试验。采用Origin软件对筛选出的最优处方释放度进行Weibull曲线拟合。考察体外释放条件对药物释放的影响。结果:优化处方为HPMC规格为K100LV,处方用量为54%,乳糖的处方用量为16%。所制得4-AP凝胶骨架片可持续释药12 h,批内释放均一性及批间重复性均良好。Weibull模型拟合方程得出药物释放符合一级速率过程。体外释放条件考察结果表明,转速对药物的释放有影响,而释放介质的种类和测定装置则无显著性影响。结论:所选4-AP凝胶骨架缓释片制备工艺可行,重复性好,有明显的缓释特性。     

愈创甘油醚缓释片的研究

目的研究1天给药2次的愈创甘油醚骨架型缓释片。方法以HPMC为骨架材料,采用正交试验设计,考察HPMC的不同型号和不同用量对释放度的影响,筛选出最佳处方。结果体外释放度实验表明,缓释片比普通片释药时间延长,其体外释放行为符合Higuchi(r=09915)方程。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。     

盐酸奥昔布宁微孔渗透泵控释片的制备及其处方优化

目的:制备盐酸奥昔布宁微孔渗透泵控释片,考察其体外释放度,并筛选出最佳处方。方法:以体外累积释放度为评价指标,分别考察渗透泵片的促渗剂含量,致孔剂含量以及包衣增重的改变对其体外释放的影响,采用响应面法优化处方,从而确定出最佳处方。结果:该控释片的体外释药由渗透压驱动的,片芯促渗剂的含量,致孔剂的用量,包衣增重对于释药行为有显著影响。结论:中心复合设计法优化的处方制备的控释片释放度符合要求,药物释药行为符合零级释放。     

包衣处方和工艺对对乙酰氨基酚缓释微丸释放度的影响

目的研究包衣处方和工艺对离心法制备的膜控型缓释微丸的体外释药行为的影响。方法以对乙酰氨基酚为模型药,采用BZJ-360型离心造粒包衣机以液相层积法制备含药丸芯,以微丸的体外释放度为考察指标,分别用单因素考察和正交试验的方法来探讨包衣处方、工艺因素对缓释微丸的释药特征的影响,并筛选出最佳水平,通过对药物释放度曲线的药动学模型拟合确定微丸的缓释机制。结果以丙烯酸树脂(Eudragit RS PO∶RL PO=10∶1)为包衣材料,包衣增重为10%,聚合物浓度为6%时包衣微丸在pH 6.2的磷酸盐缓冲液中呈现良好的缓释效果,释药机制主要是以膜控为主的扩散作用,骨架溶蚀也起到了一定的协同作用。结论该技术制备的对乙酰氨基酚缓释微丸包衣均匀,操作简便,质量可靠,可工业化生产。     

Box-Behnken响应面法优化去氧氟尿苷缓释片处方及其体外释放机制研究

目的 响应面法优化去氧氟尿苷骨架片处方,并进行体外释放机制研究。方法 以羟丙甲纤维素(HPMC K4M)为骨架材料,结合其他辅料混合均匀,以直接压片法制备去氧氟尿苷骨架缓释片。通过Box-Behnken响应面法(Box-Behnken design-response surface methodology, BBD-RSM)对处方进行优化,研究优化处方的体外释药规律,并进行数学模型拟合。结果 优化处方的去氧氟尿苷骨架缓释片体外释放性能良好,可持续释药24h,药物释放符合Ritger-peppas模型。结论 通过BBD-RSM建立的模型可用于去氧氟尿苷骨架缓释片的处方优化,优化处方达到去氧氟尿苷缓释骨架片设计要求。     

Box-Behnken效应面法筛选聚氧乙烯骨架缓释片处方和释药机制的研究

目的：优化聚氧乙烯骨架片的处方并对释药机制进行研究。方法：以水溶性药物酒石酸美托洛尔为模型药物,釆用药物与聚氧乙烯等辅料混合均匀后直接压片的方法制备聚氧乙烯骨架片。以药物释放数据的零级方程拟合度R₀²和处方在1小时和24小时的累积释药百分率Q_1h、Q_24h为评价指标。用Box-Behnken效应面法筛选最优处方。获得最优处方的释放数据进行Higuchi equation、Korsmeyer equation、Peppas-Sahlin equation方程拟合。结果：优化处方是：酒石酸美托洛尔100 mg、聚氧乙烯170 mg、卡波姆65 mg、碳酸钠102 mg,按照该处方制备的酒石酸美托洛尔聚氧乙烯骨架片,对应的评价指标测得值与预测值的偏差小于5%。经验方程拟合和各种方法验证了骨架片的药物释放是扩散和溶蚀的协同作用。结论：利用Box-Behnken效应面法筛选酒石酸美托洛尔聚氧乙烯骨架片的处方的主方法是有效可行的,模型的预测值与理论值相符。药物的释放机制是扩散和溶蚀的协同作用。     

琥珀酸去甲文拉法辛缓释片的制备及体外释药特性研究

目的 制备琥珀酸去甲文拉法辛(desvenlafaxine succinate,DVS)缓释片,确定最佳处方及制备工艺,并进行体外释放特性研究。方法 建立紫外分光光度法测定DVS缓释片的体外释放度,以体外释放度为评价指标,通过单因素考察,确定DVS缓释片的最佳处方及制备工艺。结果 最佳处方及工艺：以HPMC K15M为骨架材料,用量50%;MCC为填充剂;硬脂酸镁为润滑剂,用量8%;湿法制粒后,以70 kN的压力压片。制备的DVS缓释片体外释放行为良好,可持续释药24 h,符合试验要求。结论 DVS缓释片的制备工艺稳定可靠,体外释放度测定方法简便易行。     

酮咯酸氨丁三醇控释片的制备工艺研究及处方优化

目的:采用双层渗透泵技术制备酮咯酸氨丁三醇控释片,并应用Box-Behnken设计-效应面法获得优化处方.方法:以药物累积释放度为考察指标,采用单因素试验筛选片芯处方和包衣处方;选择2 h、16h药物累积释放度和0～16 h释药曲线的相关系数为优化指标,含药层聚氧乙烯(PEON10)用量、聚乙二醇(PEG-4000)用...     

应用Box-Behnken效应面法优化替硝唑胃漂浮片处方

目的:应用Box-Behnken效应面法优化替硝唑胃漂浮片处方。方法:采用Box-Behnken设计试验,考察羟丙基甲基纤维素(HPMC)、卡波姆及海藻酸钠三者在处方中的用量对缓释片的漂浮性能和释药性能的影响,通过二项式方程拟合因素与响应值之间的数学关系以优化处方,对体外释药数据进行方程拟合,探讨其释药机制。结果:优化处方为HPMC30%、卡波姆14%、海藻酸钠18%,优化处方的实测值与预测值之间比较接近;药物的释放模型符合Higuchi方程(r=0.9879),释药机制为骨架溶蚀与药物扩散双重作用。结论:通过Box-Behnken效应面法建立的模型可用于替硝唑胃漂浮片处方的优化。     

琥珀酸 S-美托洛尔缓释片的研制及体外释放特征探讨

目的：研制琥珀酸S-美托洛尔24 h缓释片,考察其体外释放特征,并对其体外释放机制进行初步研究。方法以羟丙基甲基纤维素（ HPMC）为骨架材料制备缓释片,以单因素试验法对缓释片释放因素进行考察,采用正交试验设计选择最佳处方,并对优化处方的释药机制进行探讨。结果最优处方以K100M和K15M规格HPMC的混合物作为骨架材料,质量分数各占总质量的20％,微晶纤维素为填充剂,质量分数占总质量的50％。制备的琥珀酸S-美托洛尔缓释片释放规律符合Ritger-Peppas方程曲线,释药行为是药物扩散和骨架溶蚀协同作用。结论琥珀酸S-美托洛尔缓释片处方合理,有良好的24 h体外释药行为,处方工艺基本满足设计要求。     

Design and characterization of colon-specific drug delivery system containing paracetamol microsponges

The present work was aimed at designing microsponge based colon specific drug delivery system containing paracetamol. Eudragit S-100 based microsponges containing drug in varying amounts were prepared using quasi-emulsion solvent diffusion method. The microsponges were prepared by optimizing various process parameters. DSC and FTIR studies indicated compatibility of the drug in various formulations. Shape and surface morphology of the microsponges were examined using scanning electron microscopy. The formulations were subjected to in vitro release studies and the results were evaluated kinetically and statistically. The in vitro release data showed a bi-phasic pattern with an initial burst effect. In the first hour drug release from microsponges was found to be between 18-30%. The cumulative percent release at the end of 12(th) hour was noted to be between 74-98%. The release kinetics showed that the data followed Higuchi model and the main mechanism of drug release was diffusion. The colon specific tablets were prepared by compressing the microsponges followed by coating with pectin: hydroxypropylmethyl cellulose (HPMC) mixture. In vitro release studies exhibited that compression coated colon specific tablet formulations started releasing the drug at 6(th) hour corresponding to the arrival time at proximal colon. The study presents a new approach for colon specific drug delivery.     

In vitro characterization and release study of Ambroxol hydrochloride matrix tablets prepared by direct compression

A series of either hydrophilic or hydrophobic polymers were used to prepare controlled release Ambroxol hydrochloride (AMX) matrix tablets by direct compression. Both the compatibility and flow properties of AMX/polymer mixtures were investigated. The effect of the amount and type of polymer on the physical properties and in vitro drug release was studied and compared to commercially available Ambroxol(?) SR capsules. A kinetic study of the release profile of AMX from the prepared matrix tablets was performed. All excipients used in the study were compatible with the model drug. AMX/drug mixtures containing sodium alginate (NA) and hydroxypropylmethyl cellulose (HPMC) showed better flow properties than other polymers used in the study. The in vitro drug release studies showed that matrix tablets formulae containing 10% HPMC (S7) or a combination of 30% NA and 5% HPMC (Ah) exhibited a higher ability to control the release of AMX. The kinetic study revealed that a diffusion controlled mechanism prevailed except when carbopol was used. Formula Ah followed a non-fickian diffusion mechanism similar to Ambroxol(?) SR capsules. Both formulae S7 and Ah could be considered as potential candidates for formulation of AMX controlled release matrix tablets.     

左卡尼汀胃漂浮缓释片的制备及体外评价

目的:应用Box-behnken效应面法优化左卡尼汀胃漂浮缓释片处方,并评价其体外漂浮和释放特性.方法:以粉末直接压片法制备片剂.采用单因素法筛选出主要影响因素,即硬度、HPMC用量及碳酸氢钠用量,以漂浮性能和不同时间点释药性能为评价指标,通过Boxbehnken设计实验优化处方,对体外释药数据进行方程拟合,并结合扫描电子显微镜对溶出前后片剂表面形态的观察,探讨其释药机理.结果:优选处方为每片含HPMCK100M 29.7％,碳酸氢钠5.0％,十八烷醇15.0％,硬度为4 kg· mm-2.体外释药符合Makoid-Banakar模型,药物的释药机制为骨架溶蚀与药物扩散双重作用.结论:Box-behnken效应面法可用于左卡尼汀胃漂浮缓释片处方优化,且制备工艺简单,优化处方具漂浮缓释作用.     

Once-daily propranolol extended-release tablet dosage form: formulation design and in vitro/in vivo investigation.

The purpose of this study was to develop and optimize the propranolol once-daily extended release formulations containing HPMC, Microcrystalline cellulose (MCC) and lactose. In vitro studies, the response surface methodology and multiple response optimization utilizing the polynomial equation were used to search for the optimal formulation with specific release rate at different time intervals. The constrained mixture experimental design was used to prepare systematic model formulations, which were composed of three formulation variables: the content of HPMC (X(1)) MCC (X(2)) and lactose (X(3)). The drug release percent at 1.5, 4, 8, 14 and 24 h were the target responses and were restricted to 15-30, 35-55, 55-75, 75-90 and 90-110%, respectively. The results showed that the optimized formulation provided a dissolution pattern equivalent to the predicted curve, which indicated that the optimal formulation could be obtained using response surface methodology. The mechanism of drug release from HMPC matrix tablets followed non-Fickian diffusion. In the vivo study, the MRT was prolonged for matrix tablets when compared with commercial immediate release tablets. Furthermore, a linear relationship between in vitro dissolution and in vivo absorption was observed in the beagle dogs.