甘草超滤液中甘草苷的络合萃取研究

目的 通过研究络合萃取剂组成变化对甘草超滤液中甘草苷萃取效果的影响,优选出适合于甘草苷萃取分离的络合萃取剂。方法 以甘草苷和甘草酸单次萃取率为指标,通过单因素实验,在考察多种二元混合络合萃取剂对甘草超滤液中指标成分萃取情况的基础上,采用U₅（5³）均匀设计优化含有2种络合剂的三元络合萃取剂,以期进一步提高甘草苷络合萃取效率,降低成本。结果 三元络合萃取剂中磷酸三丁酯（tributyl phosphate,TBP）对三烷基氧化膦（trialkyphosphine oxide,TRPO）络合萃取甘草苷没有协同萃取作用。优选15% TRPO+85%磺化煤油所组成的络合萃取剂甘草苷的单次萃取率为99.6%,甘草酸的单次萃取率为8.3%。结论 优选的络合萃取剂对甘草超滤液中甘草苷的萃取能力强、选择性高,可用于甘草超滤液中甘草苷的络合萃取。     

左旋多巴微囊漂浮片的处方优选

摘 要 目的： 优选左旋多巴微囊漂浮片的处方。方法: 高效液相色谱法测定左旋多巴与苄丝肼的含量,以漂浮片释放度得分为指标,采用正交试验优选左旋多巴微囊漂浮片的处方,并对其体外释药特性进行评价。结果: 建立的测定左旋多巴胃内漂浮片中左旋多巴与苄丝肼含量的高效液相色谱法,符合方法学要求。优化的微囊漂浮片处方组成为硬脂酸：主药：丙烯酸树脂：HPMC=2∶5∶2∶1,平均片重为550 mg。验证试验结果表明该微囊漂浮片具有漂浮、缓释、可分剂量使用等特性。结论: 优选出的复方左旋多巴微囊漂浮片处方合理,生产工艺稳定、可行。     

甲氧氯普胺口崩片的制备及体外溶出度考察

摘 要 目的： 制备甲氧氯普胺口崩片并优化处方,并对其体外溶出度进行考察。方法: 采用全因子试验设计,以填充剂配比（X₁）、崩解剂（X₂,%）用量为影响因素,以脆碎度（Y₁,%）、崩解时限（Y₂,s）、甲氧氯普胺在15 min的溶出度（Y₃,%）为片剂考察指标优化处方;并考察其在4种溶出介质中的溶出行为。结果: 甲氧氯普胺口崩片的最优处方组成为：填充剂甘露醇与微晶纤维素比例为2.5∶1、崩解剂占片重为6.5%。甲氧氯普胺口崩片在4种溶出介质中累积溶出度均大于80%。结论:甲氧氯普胺口崩片处方设计合理,制备工艺可行,质量可控。     

HPLC法同时测定妇炎愈合剂中芍药苷、丹参酮ⅡA的含量

摘 要 目的: 建立同时测定妇炎愈合剂中芍药苷、丹参酮Ⅱ_A的方法。方法: 应用高效液相色谱法测定,色谱柱为Agilent XDB C₁₈(250 mm×4.6 mm,5 μm)色谱柱;流动相为甲醇-0.2%磷酸溶液,梯度洗脱;流速为0.9 ml·min^-1,柱温35℃;检测波长230 nm（检测芍药苷）,268 nm(检测丹参酮Ⅱ_A)。结果:丹参酮Ⅱ_A、芍药苷的线性范围分别为0.516～2.581 μg（r=0.999 3）,0.364～1.819 μg（r=0.999 6）;平均加样回收率分别为96.4%（RSD=1.14%,n=5）,96.2%（RSD=1.04%,n=5）。结论:该方法简便易行、准确、重复性好,可用于妇炎愈合剂中芍药苷、丹参酮Ⅱ_A的含量测定。     

延胡索乙素胃漂浮微球的体外漂浮及释药特征评价

目的 制备延胡索乙素(tetrahydropalmatine,THP)胃漂浮微球,考察THP胃漂浮微球在不同条件下的体外漂浮性能与释药特征。方法 采用乳化溶剂挥发法制备THP胃漂浮微球,模拟胃肠道环境,通过直接观察法考察THP胃漂浮微球在0.1 mol·L^-1盐酸溶液、pH 3.0 PBS、pH 4.5醋酸缓冲液、pH 6.8 PBS释放介质,50,100,150 r·min^-1转速条件下的漂浮性能;采用转篮法考察THP胃漂浮微球在上述释放条件下的体外释放特征;以罗通定片为参比制剂,比较两者在模拟胃酸环境的体外释放特征;采用常见的动力学模型拟合延胡索乙素胃漂浮微球的释药曲线。结果 THP胃漂浮微球在不同介质中均能立即起漂,持漂12 h,漂浮率为100%;在4种释放介质中12 h累积释放度分别为(90.55±4.65)%,(81.48±5.92)%,(66.24±3.00)%,(51.93±2.35)%;在3种转速下,12 h累积释放度分别为(84.26±3.22)%,(90.55±4.65)%,(94.70±2.15)%。在模拟胃酸环境(0.1 mol·L^-1盐酸溶液)下,罗通定片0.5 h累积释放度为(78.31±11.01)%,2 h基本释放完全,而THP胃漂浮微球12 h内释药速度平稳而缓慢,无突释现象,且释药完全。结论 该研究制备的THP胃漂浮微球体外漂浮性能较好,具有较好的缓释效果,其体外释放行为符合Higuchi方程。     

升阳益胃颗粒的制备工艺研究

目的 优选升阳益胃颗粒的提取及成型工艺。方法 以甘草苷和芍药苷含量为指标,优选升阳益胃颗粒水提工艺并进行3次验证;以颗粒成品率和制粒可操作性为指标,优选润湿性和赋型剂,以160倍处方量投料中试生产3批产品。结果 升阳益胃颗粒提取工艺为水提3次,每次加8倍量水,煎煮30分钟;赋型剂为糖粉、糊精和可溶性淀粉,以低浓度乙醇制粒,颗粒剂成品率,甘草苷和芍药苷含量稳定。结论 优选的升阳益胃颗粒工艺稳定,可行。     

糖肝煎浓缩丸水提部分的提取工艺研究

摘 要 目的：优选糖肝煎浓缩丸水提部分的提取工艺参数。方法: 以芍药苷含量和浸膏得率作为评价指标, 芍药苷含量采用高效液相色谱法,色谱条件：色谱柱:WondaSil C₁₈柱(250 mm×4.6 mm,5 μm);流动相：乙腈-0.15%磷酸溶液(16∶84);流速：1.0 ml·min^-1;柱温:30℃;检测波长：230 nm。以加水量、煎煮时间和煎煮次数作为考察因素,采用正交设计法进行方差分析优选水提取工艺参数。 结果: 优选的提取工艺为加12倍量水,提取3次,每次1 h。结论:优选的提取工艺合理、稳定、可行,为糖肝煎浓缩丸提取工艺提供了试验依据。     

超临界CO2萃取优化肺痿颗粒中黄芪甲苷提取工艺的研究

目的 优化肺痿颗粒中黄芪甲苷的超临界CO₂萃取最佳工艺。方法 以黄芪甲苷的含量为指标,选取粉碎粒度、萃取时间、夹带剂浓度和夹带剂流速为影响因素,采用L₉（3⁴）正交试验法,优化提取工艺。结果 处方最佳提取工艺为粉碎粒度40目、提取时间1.5 h、夹带剂浓度95%乙醇和夹带剂流速10 mL?min^-1进行超临界萃取。结论 该优选工艺有效成分提取率高,条件可行,为肺痿颗粒工艺的优化提供科学依据。     

磷酸川芎嗪pH调控长时微孔渗透泵控释片的制备

目的 制备24 h长时释放磷酸川芎嗪微孔渗透泵控释片。方法 根据不同时间累积释放度考察药物体外释放情况;利用单因素考察和正交试验设计,筛选出最佳处方。结果 单因素考察找出对16 h内体外累积释放度影响较为显著的因素：pH调节剂（枸橼酸钠、酒石酸钠）用量、聚乙二醇-400（PEG-400）用量、柠檬酸三乙酯（TEC）用量、包衣增重。采用L₉（3⁴）正交试验的优化实验,直观分析结果得到最优处方：按照两个最佳处方进行中试放大试验制备3批样品,其体外累计释放度曲线拟合结果符合零级模型,拟合度好（r=0.995 0）,16 h累计释放度达85%以上。24 h释放结果批间相似因子（f₂）为84～97,重现性好。结论 该处方制备工艺简单有效,所制磷酸川芎嗪微孔渗透泵片在16 h内零级释放特征显著,并可达到24 h的长时控释释药。     

盐酸利多卡因长效局部注射剂的制备及质量控制

摘 要 目的：制备盐酸利多卡因长效局部注射剂,并建立其质量控制方法。方法: 采用透明质酸钠凝胶为注射剂基质,并以聚乙二醇(PEG)为交联剂增强其缓释性能,制备盐酸利多卡因长效局部注射凝胶剂,建立HPLC法测定药物含量。采用透析袋法考察盐酸利多卡因长效局部注射凝胶剂的体外累积释放度。结果:最佳处方：注射剂凝胶基质透明酸钠含量为1%,交联剂PEG4000含量为0.07%,反应温度为60℃,主药含量为20 mg·ml^-1。以交联透明质酸钠为凝胶基质的注射剂在120 h的累积释放度达95%以上,以非交联透明质酸钠为凝胶基质的注射剂在120h时已释放完全。结论:该盐酸利多卡因长效局部注射凝胶剂制备工艺简单可行,且明显具有缓释作用,其质量控制方法简便可靠。     

马钱子碱双层渗透泵控释片的研制及处方优化

目的 制备马钱子碱双层渗透泵控释片,通过正交试验优化处方,并探讨最佳处方的释药机制。方法 以累积释放度及释药曲线是否呈线性作为评价指标,单因素试验考察PEO N750、PEO Coagulant和致孔剂PEG 4000用量以及包衣增重对马钱子碱双层渗透泵控释片体外释药情况的影响。设计正交试验优化马钱子碱双层渗透泵控释片处方,并对最佳处方体外释药行为进行模型拟合。结果 正交试验结果表明,PEO N750用量对马钱子碱双层渗透泵控释片体外释药行为有显著性影响（P<0.05）,最佳处方：PEO N750 175 mg,PEO Coagulant 65 mg,PEG 4000用量为11%,包衣增重7%。马钱子碱双层渗透泵控释片最佳处方在12 h内释药速率恒定,12 h内累积释放度达93.14%。结论 研制的马钱子碱双层渗透泵控释片在12 h内具有明显的零级释放特征,可有效控制马钱子碱缓慢、恒速释放。     

阿魏酸钠胃内漂浮片的制备及体外释放机制考察

目的优化阿魏酸钠胃内漂浮片的制备工艺,并对其体外释药机理进行研究。方法以HPMC K4M为亲水性凝胶骨架,十六醇为助漂剂,NaHCO3为产气剂,采用星点设计-效应面法对处方进行优化,并通过方程拟合探讨释药机制。结果优化得到最优处方,所制得胃内漂浮片均能在1 min内起漂,持续漂浮10 h。结论采用星点设计-效应面法优化的处方预测性良好,并且所制得的胃内漂浮片具有良好的漂浮和控释能力。     

尼莫地平微粉化物双层渗透泵控释片的制备

目的 制备尼莫地平微粉化物双层渗透泵控释片。方法 以尼莫地平为模型药物,将微粉化增溶技术应用于控释双层渗透泵剂型中,设计并制备体外控释12 h的尼莫地平双层渗透泵片,采用相似因子法（f₂）对不同处方释药行为的相似性进行评价,并对处方进行优化。结果 成功制备了尼莫地平微粉化物双层渗透泵控释片,零级释放特征明显,符合渗透泵的释药机制。结论 将微粉化增溶技术与控释双层渗透泵技术相结合,显著提高了难溶性药物尼莫地平的体外释放,成功制备了控释制剂。     

美沙拉嗪肠溶缓释片的制备与体外释放度考察

目的 制备美沙拉嗪肠溶缓释片,考察其体外释放。方法 以体外释放相似因子（f₂）为主要评价指标,通过单因素处方筛选和正交试验设计得到最优处方,重现三批,比较自制美沙拉嗪肠溶缓释片与参比制剂的体外释放行为。 结果 片芯中羧甲基纤维素钠（CMC 7HXF PH）用量为45 mg,羧甲淀粉钠（CMSNa）用量为35 mg;肠溶包衣层中Eudragit L100和Eudragit S100以2:3的比例联用,包衣增重为6%。自制肠溶缓释片与参比制剂的相似因子f₂值均大于50。 结论 自制美沙拉嗪肠溶缓释片与参比制剂体外释放相似,处方工艺稳定可重现,可用于美沙拉嗪肠溶缓释片的制备。     

Formulation development and optimization of bilayer tablets of aceclofenac

Objective: The objective of the present study was to develop bilayer tablets of aceclofenac that are characterized by initial burst drug release followed by sustained release of drug.

Methods: The fast-release layer of the bilayer tablet was formulated using microcrystaline cellulose (MCC) and HPMC K4M. The amount of HPMC E4M (X₁) and MCC (X₂) was used as independent variables for optimization of sustained release formulation applying 3² factorial design. Three dependent variables were considered: percentage of aceclofenac release at 1 h, percentage of aceclofenac release at 12 h, and time to release 50% of drug (t_50%). The composition of optimum formulation of sustained release tablets were employed to formulate double layer tablets.

Results: The results indicate that X₁ and X₂ significantly affected the release properties of aceclofenac from sustained release formulation. The double layer tablets containing fast-release layer showed an initial burst drug release of more than 30% of its drug content during first 1 h followed by sustained release of the drug for a period of 24 h.

Conclusion: The double layer tablets for aceclofenac can be successfully employed as once-a-day oral-controlled release drug delivery system characterized by initial burst release of aceclofenac for providing the loading dose of drug.     

A Floating Controlled-Release Drug Delivery System: In Vitro-in Vivo Evaluation

A novel floating controlled-release drug delivery system was formulated in an effort increase the gastric retention time of the dosage form and to control drug release. The buoyancy was attributed to air and oil entrapped in the agar gel network. A floating controlled-release 300-mg theophylline tablet having a density of 0.67 was prepared and compared in vitro and in vivo to Theo-dur. The in vitro release rate of the floating tablet was slower. In vivo scintigraphic studies for a floating and a heavy nonfloating tablet, under fasting and nonfasting conditions, showed that the presence of food significantly increased the gastric retention time for both tablets, and tablet density did not appear to make a difference in the gastric retention time. However, the positions of the floating and nonfloating tablets in the stomach were very different. Bioavailability studies in human volunteers under both fasting and nonfasting conditions showed results comparable to those with Theo-dur. The floating controlled-release theophylline tablet maintained constant theophylline levels of about 2 mg/mL for 24 hr, which may be attributable to the release from the agar gel matrix and the buoyancy of the tablet in the stomach.     

Lack of In Vivo/In Vitro Correlations for 50 mg and 250 mg Primidone Tablets

Purpose. To determine if large differences in the in vitro dissolution profiles for primidone tablets would result in significant bioavailability differences. Methods. Two separate bioavailability studies were conducted. The first study used 18 healthy subjects and compared the bioavailability of an old 50 mg tablet formulation, a new 50 mg tablet formulation, and a suspension containing 50 mg/ml of primidone. The second study enrolled 24 subjects who were to receive a new 250 mg tablet formulation, two lots of an old 250 mg tablet formulation and a 250 mg tablet from a second manufacturer. In vitro dissolution was conducted over 90 minutes, using USP 23 Apparatus 2 at 50 rpm, with 900 ml of water. Results. Dissolution at 90 minutes for the old and new 50 mg tablets was approximately 20% and 100%, respectively. The dissolution of the four 250 mg tablets ranged from approximately 30% to 100%. The 50 mg tablet that dissolved slower had a longer Tmax and a 14% lower Cmax than the more rapidly dissolving tablet, but the AUC(0–) values differed by only 3%. Only nine subjects completed the 250 mg study because of side effects. The differences in Cmax and AUC(0–) among the four 250 mg tablets were less than 7%. Conclusions. Even though there were large differences in the in vitro dissolution of the 50 mg and the 250 mg primidone tablets, the two 50 mg tablets were shown to be bioequivalent, as were the four 250 mg tablets.     

Design,Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology

The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 3² full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D_{1 h,}D_{6 h}) and time required to 90% drug release (t_90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.     

Development of gastroretentive drug delivery system for cefuroxime axetil: In vitro and in vivo evaluation in human volunteers

The objective of this investigation was to develop the cefuroxime axetil sustained-release floating tablets to prolong the gastric residence time and compare their pharmacokinetic behavior with marketed conventional tablets (Zocef). The floating tablets were developed using polymers like HPMC K4M and HPMC K100M alone, and polymer combination of HPMC K4M and Polyox WSR 303 by effervescent technique. Tablets were prepared by slugging method and evaluated for their physical characteristics, in vitro drug release, and buoyancy lag time. The best formulation (F10) was selected based on in vitro characteristics and used in vivo radiographic and bioavailability studies in healthy human volunteers. All the formulations could sustain drug release for 12 h. The dissolution profiles were subjected to various kinetic release models and it was found that the mechanism of drug release followed Peppas model. The in vivo radiographic studies revealed that the tablets remained in stomach for 225±30 min. Based on in vivo performance, the developed floating tablets showed superior bioavailability than Zocef tablet. Based on in vivo performance significant difference was observed between C_max, t_max, t_1/2, AUC_0–∞, and mean residence time of test and reference (p<0.05). The increase in relative bioavailability of test was 1.61 fold when compared to reference.     

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.