非洛地平-美托洛尔复方透皮贴剂的基础处方优化

以贴剂外观和黏性为指标，通过正交设计考察非洛地平和美托洛尔的投料量、复合压敏胶材料Eudragit E PO和Eudragit RL PO重量比、增塑剂（PEG 400）和交联剂（琥珀酸）用量等因素对贴剂质量的影响。优选的基础处方为：非洛地平和美托洛尔投料量分别为2％和20％、Eudragit E PO-Eudragit RL PO为5：5（w／w）、PEG 400和琥珀酸用量分别为10％和12％。结果表明，该处方制备的贴剂外观良好，黏性适宜，药物体外释放速率和稳态透皮速率较高。     

非洛地平/美托洛尔复方贴剂体外透皮特性及皮肤刺激性考察

目的 制备非洛地平/美托洛尔复方透皮贴剂,考察其对离体兔皮的经皮渗透性及对家兔皮肤的刺激性.方法 采用改良的Franz透皮扩散装置,以离体兔皮为渗透屏障,NS-乙醇(6040)为接受液,用HPLC法同时测定经皮渗透液中两药浓度并计算其渗透动力学参数.通过皮肤刺激性试验法考察该贴剂对家兔皮肤的刺激性.结果 非洛地平/美托洛尔复方透皮贴剂中非洛地平和美托洛尔48h内均以零级动力学经兔皮转运,并具一定同步性;该贴剂对家兔皮肤无刺激性.结论 非洛地平/美托洛尔复方透皮贴剂缓释长效特征明显,药物体外经皮渗透性较好且稳定,符合经皮给药系统应对皮肤无刺激性的设计要求.     

白芷香豆素黏胶分散型贴剂的制备及体外经皮渗透研究

目的 制备白芷香豆素黏胶分散型贴剂,考察其离体皮肤渗透性和物理性状,筛选贴剂处方,提高白芷香豆素的透皮吸收速率。方法 将白芷香豆素分散于尤特奇压敏胶中,采用流涎工艺制备黏胶分散型贴剂。用Franz扩散池进行乳猪离体皮肤渗透实验,用HPLC测定欧前胡素的含量,考察了白芷香豆素含量、促渗剂的种类和用量、压敏胶的种类和用量、工艺参数对药物稳态透皮速率和贴剂的物理性状的影响。结果 优选出最佳处方为：药物含量1.0 mg·cm^-2,Eudragit E100 9 mg·cm^-2,油酸0.6 mg·cm^-2;固化时间为40 min,稳态透皮速率达到0.82 μg·cm^-2·h^-1。结论 制得的黏胶分散性白芷香豆素贴剂有较高的经皮渗透速率和较好的物理性状,优选出的处方及工艺稳定、可行。     

非洛地平-美托洛尔复方贴剂经不同动物皮肤的药物渗透性

目的制备非洛地平-美托洛尔复方透皮贴剂并研究经不同动物皮肤的体外药物渗透特性。方法采用改良的Franz透皮扩散装置,分别以离体小鼠、大鼠和兔皮肤为渗透屏障,生理盐水-乙醇(60:40)为接受液,用HPLC同时测定经皮渗透液中两药物的浓度,并计算渗透动力学参数。结果贴剂中,非洛地平和美托洛尔48 h内均以零级动力学经不同动物皮肤转运,并具一定同步性,动物皮肤对药物渗透性依次为:小鼠>大鼠>兔。结论非洛地平-美托洛尔复方透皮贴剂缓释长效特征明显,药物体外经皮渗透性稳定,各指标均可满足治疗血药浓度的要求。     

复方葛根透皮贴剂的制备工艺研究

目的:优化复方葛根经皮给药系统的制剂处方,确定最佳制备工艺。方法:采用单因素试验确定以流涎法制作骨架型复方葛根经皮给药系统的最佳制备工艺。采用均匀实验设计,以葛根素、川芎嗪和丹参酮ⅡA的24 h累积体外透皮总量和透皮速率为考察指标优选复方葛根透皮贴剂的最佳处方。结果:确定制剂处方中含量分别为PVA4.41%、PVP 31.30%、甘油2.16%、压敏胶3.63%、氮酮5.09%、丙二醇2.50%。最佳制备工艺为基质混合加10倍水搅拌均匀,药物以10倍量80%乙醇溶解,与上述基质混合均匀,以流涎法制备贴剂。结论:该制备工艺科学合理,质量稳定,是复方葛根透皮贴剂的最佳制备工艺。     

广藿香酮透皮贴剂成型工艺探讨

目的:制备广藿香酮透皮贴剂并优化其处方。方法:通过单因素考察,筛选透皮贴剂的压敏胶基质组成及载药量,采用均匀设计法筛选贴剂透皮促进剂。结果:采用压敏胶A为控释骨架和压敏胶材料,载药量为4%。透皮促进剂最优组合为月桂氮芯卓酮-油酸-丙二醇为6%∶5%∶5%。药物从压敏胶层恒速释放。结论:所研制的透皮贴剂具有理想的释药特性。     

非洛地平-美托洛尔复方经皮给药系统的制备及其兔体内生物利用度

制备了非洛地平-美托洛尔复方经皮给药系统，并研究其药剂学性质及经兔皮肤给药的药代动力学和生物利用度。先建立了同时测定贴剂和经皮渗透液中非洛地平与美托洛尔含量的RP-HPLC方法，以考察贴剂的药物体外稳态透皮速率和经皮渗透机制，并进行质量控制和评价；再以高灵敏度的GC-ECD方法分别测定非洛地平和美托洛尔的血药浓度，研究贴剂经皮给药后在兔体内的药代动力学和生物利用度。结果显示，该给药系统的复方药物体外透皮转运具有零级动力学特征，其含量均匀度检查符合2005版中国药典规定，稳定性好；经皮给药的血药浓度明显较口服平稳，且波动性小，达峰时间推后，持效时间延长，非洛地平与美托洛尔的相对生物利用度分别为275.37%和189.76%。以上结果表明，非洛地平-美托洛尔复方经皮给药系统具有明显缓释特征，可较长时间维持稳定有效的血药浓度。     

非洛地平-美托洛尔复方经皮贴剂单次给药降压作用研究

目的评价非洛地平-关托洛尔复方经皮贴剂的降压作用。方法研制非洛地平-关托洛尔复方透皮给药系统，并将其应用于高血压大鼠，进行药效学评价。结果单次给药后，3个剂量组对收缩压、舒张压和心率的影响均呈剂量依赖性降低，分别与空白对照组和灌胃给药组比较，均有显著性差异（P〈0．05）。结论非洛地平-美托洛尔复方透皮贴剂的降压效果确切，降压作用平稳，持续时间长；其降压作用强度和持续时间具有剂量依赖性，降压效果优于非洛地平和美托洛尔的口服给药。     

白头翁素贴片的制备与体外经皮渗透试验

目的制备白头翁素贴片，为白头翁素经皮制剂的开发提供依据。方法采用Eudragit E100为骨架材料，流涎工艺制备骨架型贴片。以HPMC醇性凝胶为储库递质，EVA为控释膜，热封法制备储库型贴片。采用TK 6A型透皮扩散仪，用人皮进行体外渗透实验；采用高效液相色谱法测定各时间点接受室中药物浓度，求算经皮渗透的相关参数。结果白头翁素骨架型贴剂经皮给药的稳态透皮速率［(1.72±0.02) mg·(cm2) 1·h 1］是其饱和水溶液的1.47倍，是储库型贴剂的2.30倍。结论白头翁素骨架型贴剂制备简单，具有较高的经皮渗透速率，有望开发成一种新型的经皮给药制剂。     

驻极体氟尿嘧啶凝胶贴剂的制备研究

目的 制备并优化驻极体氟尿嘧啶凝胶贴剂及考察贴剂的相关性质。方法 通过预实验筛选黏合剂和保湿剂,采用正交设计优化处方,用补偿法测量驻极体贴剂的电荷储存稳定性,用透皮扩散仪和HPLC仪研究药物的体外透皮作用。结果 贴剂基质的最佳配比为PAAS∶明胶∶PVA∶高岭土∶CMC-Na∶保湿剂=0.2∶0.7∶0.5∶0.7∶0.2∶12;制备的贴剂具有良好的电荷储存稳定性;驻极体和3%氮酮均能有效地促进药物释放,且两者有协同促渗作用。结论 按最佳条件制备了质量优良的驻极体氟尿嘧啶凝胶贴剂,该贴剂对皮肤无刺激性,且该贴剂的药物释放行为优于一般的凝胶贴剂。     

Eudragits: role as crystallization inhibitors in drug-in-adhesive transdermal systems of estradiol.

A transdermal steroidal delivery system usually contains a high concentration of drug to obtain high drug fluxes. The present investigation involved the development of drug-in-adhesive transdermal systems of estradiol using synthesized acrylate copolymer (EA) of 2-ethylhexyl acrylate and acrylic acid. The effect of several variables such as varying drug polymer ratios, effect of Eudragit RL PO and Eudragit E PO and effect of drying temperatures on prevention of drug crystallization in the formulation matrix was investigated. The systems free from drug crystals were evaluated and compared with a marketed formulation with respect to its skin permeation profile. The optimized formulation was also subjected to accelerated stability testing. Eudragit RL PO and Eudragit E PO were found to be effective as crystallization inhibitors in the transdermal matrix systems tested. Formulations fabricated with Eudragit E PO gave transparent systems with good film properties and a higher skin permeation profile as compared to that of the marketed system. Higher temperature and humidity conditions facilitated the formation of drug crystals, whereas no crystals were observed in the formulation matrix at 23+/-0.5 degrees C and at 30+/-1 degrees C for the period of 6 months studied.     

Novel biomaterial for transdermal application: in vitro and in vivo characterization

The objective of the present study was to evaluate a novel film forming biomaterial for its potential application in the preparation of unilaminate transdermal adhesive matrix systems. The biomaterial, Damar Batu (DB), was tried alone and in combination with Eudragit RL100 as a matrixing agent in the preparation of transdermal patches. Developed transdermal patches of Diltiazem hydrochloride (DH) were evaluated for thickness uniformity, weight uniformity, folding endurance and drug content. USP dissolution apparatus V was used for in vitro drug release studies. Modified Franz diffusion cell used for permeation study using excised human cadaver skin. Total 6 formulations were developed and on the basis of in vitro drug release and in vitro skin permeation profile F5 composed of DB: Eudragit RL100 (60:40) and carrying 20 %w/w DH was selected as an optimized formulation for in vivo study. The in vivo study results showed that F5 achieved the Cmax of about 269.76 ± 1.52 ng/mL in 6 h and sustained the release of the drug till 24 h. The skin irritation study results proved that the novel biomaterial is non-sensitizing and non-irritating. Drug-polymer interaction study carried out to check the compatibility of drug and polymer showed the intactness of the drug in the formulation proving the compatibility of the polymer. It can be proposed from the outcome of the present study that by applying suitable adhesive layer and backing membrane, DB: Eudragit RL100 (60:40) transdermal patches can be of potential therapeutic use.     

非洛地平和美托洛尔联用大鼠经皮给药的协同降压作用

目的：研究非洛地平和美托洛尔联用经皮给药对自发性高血压大鼠的协同降压作用，为其复方经皮给药系统的研制提供药理学依据。方法：50只自发性高血压大鼠随机分为10组（均为单次给药）：空白对照组，非洛地平-美托洛尔剂量分别为1-10、3—30、9—90mg／kg的复方透皮贴剂治疗组，非洛地平剂量分别为1、3、9mg／kg和美托洛尔剂量分别为10、30、90mg／kg的单方透皮贴剂治疗组。以无创性尾套法测定给药后大鼠的血压和心率，评价两药联用的协同降压作用。结呆：非洛地平和美托洛尔联用经皮给药对收缩压和舒张压的降低作用均显著高于两药各自单用（P〈0．05），对心率有降低作用但显著低于单用美托洛尔（P〈0．05）。单方与复方药物经皮给药对血压及心率的作用强度和持续时间均具有剂量依赖性（P〈0．05）。结论：作用机制不同的非洛地平和美托洛尔联用，协同和互补作用明确，该透皮给药复方制剂可以提高血压控制率、治疗安全性和病人用药依从性。     

奥昔布宁透皮贴剂的制备及其体外透皮性研究

目的：制备奥昔布宁透皮贴剂,并对其体外透皮性进行研究。方法：以奥昔布宁为主药,聚丙烯酸树脂E100为辅料,制备奥昔布宁透皮贴剂。采用高效液相色谱法,比较不同渗透促进剂（3％、5％氮酮,5％、10％、15％三醋酸甘油酯,5％、10％肉豆蔻酸异丙酯）对奥昔布宁透皮贴剂的稳态透皮速率（z）的影响,选出最佳渗透促进剂;采用正交试验法,以上和初黏力、持黏力为指标．考察增塑剂癸二酸二丁酯、交联剂丁二酸用量和载药量对贴剂透皮性的影响,优化最佳处方。结果：最佳渗透促进剂为15％三醋酸甘油酯;最优处方为增塑剂25％、交联剂6％、载药量25％;制备的奥昔布宁透皮贴剂的体外为6．24gg／（cm2·h）,初黏力为22号钢珠,持黏力为81min。结论：制备的奥昔布宁透皮贴剂具有良好的透皮性。     

Novel Biomaterial for Transdermal Application: In vitro and In vivo Characterization

The objective of the present study was to evaluate a novel film forming biomaterial for its potential application in the preparation of unilaminate transdermal adhesive matrix systems. The biomaterial, Damar Batu (DB), was tried alone and in combination with Eudragit RL100 as a matrixing agent in the preparation of transdermal patches. Developed transdermal patches of Diltiazem hydrochloride (DH) were evaluated for thickness uniformity, weight uniformity, folding endurance and drug content. USP dissolution apparatus V was used for in vitro drug release studies. Modified Franz diffusion cell used for permeation study using excised human cadaver skin. Total 6 formulations were developed and on the basis of in vitro drug release and in vitro skin permeation profile F5 composed of DB: Eudragit RL100 (60:40) and carrying 20 %w/w DH was selected as an optimized formulation for in vivo study. The in vivo study results showed that F5 achieved the Cmax of about 269.76?±?1.52?ng/mL in 6?h and sustained the release of the drug till 24?h. The skin irritation study results proved that the novel biomaterial is non-sensitizing and non-irritating. Drug-polymer interaction study carried out to check the compatibility of drug and polymer showed the intactness of the drug in the formulation proving the compatibility of the polymer. It can be proposed from the outcome of the present study that by applying suitable adhesive layer and backing membrane, DB: Eudragit RL100 (60:40) transdermal patches can be of potential therapeutic use.     

Mucoadhesive fenretinide patches for site-specific chemoprevention of oral cancer: enhancement of oral mucosal permeation of fenretinide by coincorporation of propylene glycol and menthol

The objective of this study was to enhance oral mucosal permeation of fenretinide by coincorporation of propylene glycol (PG) and menthol in fenretinide/Eudragit RL PO mucoadhesive patches. Fenretinide is an extremely hydrophobic chemopreventive compound with poor tissue permeability. Coincorporation of 5-10 wt % PG (mean J(s) = 16-23 μg cm?2 h?1; 158-171 μg of fenretinide/g of tissue) or 1-10 wt % PG + 5 wt % menthol (mean J(s) = 18-40 μg cm?2 h?1; 172-241 μg of fenretinide/g of tissue) in fenretinide/Eudragit RL PO patches led to significant ex vivo fenretinide permeation enhancement (p < 0.001). Addition of PG above 2.5 wt % in the patch resulted in significant cellular swelling in the buccal mucosal tissues. These alterations were ameliorated by combining both enhancers and reducing PG level. After buccal administration of patches in rabbits, in vivo permeation of fenretinide across the oral mucosa was greater (～43 μg fenretinide/g tissue) from patches that contained optimized permeation enhancer content (2.5 wt % PG + 5 wt % menthol) relative to permeation obtained from enhancer-free patch (～17 μg fenretinide/g tissue) (p < 0.001). In vitro and in vivo release of fenretinide from patch was not significantly increased by coincorporation of permeation enhancers, indicating that mass transfer across the tissue, and not the patch, largely determined the permeation rate control in vivo. As a result of its improved permeation and its lack of deleterious local effects, the mucoadhesive fenretinide patch coincorporated with 2.5 wt % PG + 5 wt % menthol represents an important step in the further preclinical evaluation of oral site-specific chemoprevention strategies with fenretinide.     

吡喹酮脂质体凝胶的研制及其体外透皮扩散研究

目的：研制吡喹酮（PQ）的脂质体凝胶（PQ—LG）,并对其体外释药特性进行考察。方法：薄膜分散法制备PQ脂质体,以泊洛沙姆-407为凝胶基质,研制PQ—LG。采用均匀设计对PQ—LG的处方及制备工艺进行优化,对其体外主要性质进行考察,并采用鼠皮为吸收屏障,对其体外透皮透皮速度及程度进行评价。结果：PQ—LG的最佳处方及工艺条件为：类脂／药物为20：1,pH为6．5,蒸发温度为45℃,水化时间为30min。体外性质表明PQ—LG外形圆整,平均粒径为（866．6±18．8）nm,平均包封率（ER）为74．33±1．95％（n=3）;体外透皮实验表明PQ．LG的透皮累积透过量Q符合Higuehi方程：Q=34．15t1/2 2．76（r=0．9948）,与PQ凝胶相比,Q及稳态透皮速率J均有明显提高（P〈0．05）。结论：PQ—LG具有制备简单,质量理想,透皮吸收好等特点,值得进一步进行体内研究。     

酒石酸美托洛尔缓释微丸的制备及处方因素考察

目的：选用Eudragit RS 30 D与Eudragil RL30D两种包衣材料，制备日服2次的酒石酸美托洛尔缓释徽丸，并对其处方因素进行考察。方法：采用Glatt流化床底喷溶液上药法制备载药微丸，考察缓释聚合物Eudragit RS 30D与Eudragit RL 30D的不同质量配比（2：3，7：3和9：1）、聚合物包衣增重（10％，20％和30％）以及增塑利嗣量（10％，20％和40％）和放置时间对药物释放的影响。结果：当Eudragit RS 30D与Eudragit RL 30D的质量比为9：1，聚合物包衣增重为20％，增塑剂用量为20％时，药物的释放行为符合中国药典对缓释制剂释放度的相关规定。结论：通过调整Eudragit RS 30D与Eudragit RL 30D之间的比例，或提高聚合物包衣增重等手段，能使酒石酸美托洛尔载药徽丸具备较理想的缓释效果。     

伊曲康唑固体脂质纳米粒的制备

目的:制备伊曲康唑固体脂质纳米粒,并考察其理化性质.方法:采用乳化-低温固化法制备伊曲康唑固体脂质纳米粒(ITZ-SLN);在脂质、表面活性剂等辅料和主药用量的单因素考察基础上,以包封率为评价指标,采用正交试验设计,优化处方组成和制备工艺;用低温超速离心法测定包封率,透射电镜观察形态,激光粒径分析仪测定粒径和ξ电位.结果:脂质、表面活性剂和主药的用量对ITZ-SLN包封率均有不同程度的影响.以优化处方制备的伊曲康唑固体脂质纳米粒为类球形实体,粒径分布比较均匀,平均粒径为dav=(118.2±15.00)nm,ξ电位(-37.06±0.53)mV,包封率(92.11±1.60)%.结论:乳化-低温固化法制备伊曲康唑固体脂质纳米粒工艺可行.     

Eudragit-based transdermal delivery system of pentazocine: Physico-chemical, in vitro and in vivo evaluations

The present study was aimed to develop a matrix-type transdermal formulation of pentazocine using mixed polymeric grades of Eudragit RL/RS. The possible interaction between drug and polymer used were characterized by FTIR, DSC and X-RD. X-RD study indicates a change of state of drug from crystalline to amorphous in the matrix films prepared. The matrix transdermal films of pentazocine were evaluated for physical parameters and in vitro dissolution characteristic using Cygnus' sandwich patch holder. Irrespective of the grades of Eudragit polymer used, the thickness and weight per patch were similar. In vitro dissolution study revealed that, with an increase in the proportion of Eudragit RS (slightly permeable) type polymer, dissolution half life (t(50%)) increases and dissolution rate constant value decreases. Selected formulations were chosen for these pharmacokinetic studies in healthy rabbits. The relevance of difference in the in vitro dissolution rate profile and pharmacokinetic parameters (C(max), t(max), AUC((s)), t(1/2,) K(el), and MRT) were evaluated statistically. In vitro dissolution profiles (DRC and t(50%)) and pharmacokinetic parameters showed a significant difference between test products (P?相似文献