甲睾酮凝胶剂的制备与含量测定

目的:制备甲睾酮凝胶剂,并建立其含量测定方法。方法:以甲睾酮为主药,卡波姆940、67%乙醇、肉豆蔻酸异丙酯等为基质,制备凝胶剂;采用高效液相色谱法测定甲睾酮的含量。结果:所制制剂为澄清透明凝胶;甲睾酮检测浓度的线性范围为2.0～8.0μg·mL-1,平均回收率为99.84%,RSD=0.62%(n=5)。结论:该制剂制备工艺可行,含量测定方法具有较好的专属性和精确度。     

不同基质及促渗剂对奥氮平贴剂体外透皮吸收的影响

目的:研究不同基质及促渗剂对奥氮平贴剂体外透皮促渗作用的影响.方法:采用不同基质及促渗剂制备奥氮平贴剂;采用卧式双室扩散池,以离体大鼠皮肤为模型,通过HPLC法测定药物浓度,拟合奥氮平透皮吸收的累积透过量和透过速率.结果:由Duro-Tak 87-4098型压敏胶制备的贴剂具有较好的稳态渗透速率,5%薄荷脑+10%肉豆蔻酸异丙酯合用对奥氮平促渗效果明显,促渗倍率达5.86倍.结论:奥氮平在以5%薄荷脑+10%肉豆蔻酸异丙酯为促渗剂,Duro-Tak 87-4098型压敏胶为基质时具有较好的透皮吸收.     

不同基质及促渗剂对氢溴酸高乌甲素凝胶经皮渗透的影响

［摘要］目的 研究不同凝胶基质及促渗剂对氢溴酸高乌甲素经皮吸收的影响. 方法 分别用羟丙基甲基纤维素和卡波姆934作为凝胶基质制备氢溴酸高乌甲素凝胶,并加入月桂氮卓酮或油酸作为经皮吸收促进剂,采用TK－12A型透皮扩散池测定并比较其吸收速率. 结果 与羟丙基甲基纤维素凝胶比较,以卡波姆934作为凝胶基质的氢溴酸高乌甲素其经皮渗透效果较好. 加入3%月桂氮卓酮+乙醇作为复合促渗剂能显著促进氢溴酸高乌甲素卡波姆凝胶中药物的吸收,3%油酸对药物的经皮渗透影响不大. 结论 氢溴酸高乌甲素在以3%月桂氮卓酮和乙醇为复合促渗剂,卡波姆为基质的凝胶剂中具有较好的经皮渗透效果.     

白藜芦醇三甲醚乳胶体外经皮渗透研究

目的制备白藜芦醇三甲醚(BTM)乳胶,考察载药量、促渗剂及其组合对BTM经皮渗透性的影响,评价药物透皮给药的可行性。方法以卡波姆940为凝胶基质制备BTM乳胶,选用改良Franz扩散池,以离体乳猪腹部皮肤为屏障进行体外经皮渗透实验,用HPLC-UV法测定各时间点接收室中药物浓度,计算经皮渗透动力学参数。结果载药量由1%增加到2%时,BTM 24 h单位面积渗透量增加1倍,2%与4%乳胶渗透量没有统计学差异(P>0.1)。促渗剂均可显著促进BTM透皮吸收,其透皮速率为:2%香叶醇>2%肉豆蔻酸异丙酯>2%油酸>2%氮酮>2%橙花叔醇>无促渗剂;香叶醇的浓度大小对BTM的透皮吸收无明显影响(P>0.05);与单用2%香叶醇相比,促渗剂联用(2%香叶醇+2%丙二醇、2%香叶醇+2%肉豆蔻酸异丙酯)未显示出显著协同促渗作用(P>0.05),而2%香叶醇+2%异丙醇则显示弱拮抗促渗作用(P<0.05)。结论常用促渗剂均能不同程度促进BTM经皮渗透,载药量为2%、促渗剂为2%香叶醇时,BTM体外透皮可达最大吸收。但BTM体外透皮吸收具有饱和性,该结果为BTM经皮给药研究提供了基础。     

香叶木苷凝胶剂的制备及体外释药特性研究

目的:筛选香叶木苷凝胶剂的最优处方,并考察其体外释药特性。方法:以卡波姆940为基质制备香叶木苷凝胶剂;以累积释放率为考察指标,卡波姆940、乙醇、丙三酮用量以及pH值为考察因素设计L9(34)正交试验,优化香叶木苷凝胶剂的处方并验证。以香叶木苷软膏剂为参照,采用透析袋扩散法考察按最优工艺所制香叶木苷凝胶剂的体外释药特性。结果:香叶木苷凝胶剂最优处方为卡波姆940 1.5 g、乙醇15 m L、丙三醇8 g、pH 6。按最优处方所制凝胶剂呈黏稠状棕黄色半固体,涂展性良好;释药2 h时的平均累积释放率为(12.67±0.12)%。体外释药试验结果显示,香叶木苷凝胶剂在12 h内释放较快,然后逐渐放缓,12、24 h时的累积释放率分别为(71.93±0.42)%、(80.47±0.54)%,其释药符合Higuchi方程;香叶木苷软膏剂释放较慢,12、24 h时的累积释放率分别为(41.74±0.18)%、(62.63±0.59)%,其释药符合一级方程。结论:成功优化了香叶木苷凝胶剂的处方;所得香叶木苷凝胶剂释药性良好。     

正交试验优化复方粉背雷公藤凝胶剂处方

目的:优化复方粉背雷公藤凝胶剂处方。方法:以成型性、光泽度、均匀度、黏度、pH、涂展性、稳定性等组成的综合评分(总分15.0分)为指标,以卡波姆940、丙二醇、三乙醇胺及药材提取液等在处方中的用量为考察因素,设计正交试验优化复方粉背雷公藤凝胶剂处方,并进行验证试验。结果:优化处方为卡波姆940 1.0 g、氮酮2.0 g、亚硫酸氢钠0.4 g、提取液50 m L、丙二醇10g、三乙醇胺1.0 g,加水至100 g。验证试验结果显示所制凝胶综合评分均值为14.8(RSD=1.35%,n=3)。结论:优化处方所制复方粉背雷公藤凝胶成型性好,质量符合要求。     

左氧氟沙星凝胶的制备及质量控制

目的:制备左氧氟沙星凝胶剂并制定质控标准.方法:以卡波姆940为基质,三乙醇胺为中和剂制成凝胶剂;采用反相高效液相色谱法测定凝胶中左氧氟沙星的含量.结果:含量测定线性回归方程为A=7.51×104C 3.71×104(r=0.999 9),线性范围4.0～20μg·ml-1.平均回收率99.7%,RSD0.57%.结论:该凝胶剂处方合理,质量稳定,适于临床应用.     

基质pH及促渗剂对阿昔洛韦水凝胶贴剂体外透皮性能的影响

分别制备了基质pH为5.0、6.0、7.5的不含促渗剂的阿昔洛韦水凝胶贴剂,在基质pH 6.0的处方中加入不同浓度的月桂氮革酮、Ⅳ.甲基吡咯烷酮(NMP)、薄荷醇、吐温-80、聚乙二醇(PEG)400作为促渗荆,以考察基质pH及促渗剂对阿昔洛韦透过离体小鼠皮肤的影响.结果表明,基质pH升高,阿昔洛韦的透皮速率增大.与不含促渗剂的基质pH6.0处方组对照,NMP、PEG 400单用不能提高阿昔洛韦的渗透速率,4%的吐温-80、薄荷醇和月桂氮革酮均可提高阿昔洛韦的经皮渗透.     

蛇床子素凝胶剂的处方优选研究

目的优化蛇床子素凝胶剂的处方。方法采用Franz扩散池,以离体大鼠腹部皮肤为透皮屏障,用高效液相法测定接受液中蛇床子素的含量,考察不同浓度卡波姆、不同促渗剂单用及合用对经皮渗透的影响,以透皮速率Jss为指标优化蛇床子素凝胶剂处方,并对蛇床子素凝胶剂物理性质进行表征。结果 0.5%卡波姆的透皮速率较高;几种不同的促渗剂对蛇床子素凝胶剂透皮吸收具有促进作用,促渗剂单用考察中,氮酮:3%>5%>1%,油酸:5%>1%>10%,冰片:3%>5%>1%,合用考察中:5%异丙醇+3%冰片>5%,2%异丙醇+3%氮酮>3%氮酮+5%油酸。结论 5%异丙醇与3%冰片合用后,促渗效果较二者单用表现明显的协同作用,为蛇床子素经皮给药制剂处方设计提供依据。     

正交设计石榴鞣花酸凝胶剂处方配比的研究

目的 采用正交设计法对石榴中鞣花酸凝胶处方配比进行优化。方法 采用正交分析法,以丙二醇、卡波姆-940以及凝胶pH水平作为影响因素,评估指标为凝胶剂鞣花酸均匀性、外观形状、涂展性以及离心性,通过筛选选出最优配比。结果 1.5%的卡波姆-940、15%的丙二醇以及控制凝胶pH在4.0～5.0范围内其各项指标达到最优。结论 经过正交设计优化后的凝胶剂其工艺方法简单且稳定可靠,具有生产可行性。     

复方血竭凝胶基质成型工艺分析

目的研究制定复方血竭凝胶基质成型工艺,确定适宜的基质及其配比。方法在查阅文献及预实验的基础上确定复方血竭凝胶基质的种类及用量范围,以制剂的均匀性、凝固性、手感、色泽、耐热、耐寒情况等方面作为考察指标进行综合评分,采用L9（34）正交实验优选其基质的配比。结果优选的复方血竭凝胶基质配比为：卡波姆940 1%,甘油30%,三乙胺醇15%,氮酮、乙醇适量。结论研制的复方血竭凝胶具有良好的涂展性,主药含量高、稳定性好。通过制剂成型工艺为中药复方血竭凝胶的进一步开发奠定了良好的基础。     

Effects of vehicles and enhancers on transdermal delivery of clebopride

The effects of vehicles and penetration enhancers on the skin permeation of clebopride were evaluated using Franz type diffusion cells fitted with excised rat dorsal skins. The binary vehicle system, diethylene glycol monoethyl ether/isopropyl myristate (40/60, w/w), significantly enhanced the skin permeation rate of clebopride. The skin permeation enhancers, oleic acid and ethanol when used in the binary vehicle system, resulted in relatively high clebopride skin permeation rates. A gel formulation consisting of 1.5% (w/w) clebopride, 5% (w/w) oleic acid, and 7% (w/w) gelling agent with the binary vehicle system resulted in a permeation rate of 28.90 microg/cm2/h. Overall, these results highlight the potential of clebopride formulation for the transdermal route.     

酮咯酸氨丁三醇凝胶剂体外经皮渗透研究

目的：考察凝胶剂作为酮咯酸氨丁三醇透皮给药载体的可行性。方法：制备卡波姆940药物凝胶，采用Franz扩散池用离体大鼠皮肤进行体外经皮渗透实验，以HPLC法测定渗透介质中药物含量并求算累积渗透量及稳态透皮速率。结果：以1．0％卡波姆940为凝胶基质，以硼砂溶液调节凝胶的pHN6．0时所制备的凝胶为最佳凝胶基质。3％的月桂氮革酮及5％的丙二醇均可以显著提高凝胶中药物的经皮渗透，且两者联用存在协同作用。结论：本实验的凝胶基质可为生产提供参考依据。     

Feasibility studies of dermal delivery of paclitaxel with binary combinations of ethanol and isopropyl myristate: role of solubility, partitioning and lipid bilayer perturbation

In the current investigation, paclitaxel (PCL) delivery into the different layers of skin, vehicle optimization and relationship between vehicle composition and the relative contribution of solubility, partition and diffusion towards drug transport has been outlined. Saturation solubility of PCL was determined in ethanol (EtOH), isopropyl myristate (IPM) and their binary combinations, and partition studies performed to study the probability of skin depot formation. Epidermal and dermal partitioning was carried from PCL saturated vehicles. Skin permeation of PCL was studied using the rat skin. FT-IR has been utilized to study the skin barrier perturbation, and the localization of PCL and isopropyl myristate (IPM) in epidermis. High K(app) value in mineral oil/buffer indicated the tendency of PCL to form a reservoir in skin, and an inverse relationship between PCL solubility in different solvent systems and partitioning into epidermis was found. Maximum K(epidermis) for PCL was observed with IPM, while PCL in EtOH/IPM (1:1) showed high partitioning into dermis. Maximum flux of PCL was observed with EtOH/IPM (1:1). For lipophilic drug like PCL modulation of vehicle seems to be effective approach to increase the permeability across the skin. With a binary combination of EtOH/IPM (1:1) higher concentration of PCL can be delivered to deeper layer of skin whereas with IPM higher concentration of PCL could be localized in the epidermis. While engineering the delivery vehicle selection of solvents should be such that one of them is miscible in both hydrophilic and lipophilic phase like ethanol and another should be lipophilic in nature (IPM in this case) so that an optimum balance between 'push-pull' and 'blending' effect can be achieved.     

Skin permeation of testosterone and its ester derivatives in rats

To establish the optimum conditions for improving the transdermal delivery of testosterone, we studied the relationship between the lipophilicity of testosterone ester derivatives and the rat skin permeation rate of testosterone. We performed a rat skin permeation study of testosterone and its commercially available ester derivatives, testosterone hemisuccinate, testosterone propionate and testosterone-17beta-cypionate, using an ethanol/water co-solvent system. The aqueous solubility and rat skin permeation rate of each drug, saturated in various compositions of an ethanol/water system, was determined at 37 degrees C. The aqueous solubility of testosterone and its ester derivatives increased exponentially as the volume fraction of ethanol increased up to 100% (v/v). The stability of testosterone propionate in both the skin homogenate and the extract was investigated to observe the enzymatic degradation during the skin permeation process. Testosterone propionate was found to be stable in the isotonic buffer solution and in the epidermis-side extract for 10h at 37 degrees C. However, in the skin homogenate and the dermis-side extract testosterone propionate rapidly degraded producing testosterone, implying that testosterone propionate rapidly degraded to testosterone during the skin permeation process. The steady-state permeation rates of testosterone in the ethanol/water systems increased exponentially as the volume fraction of ethanol increased, reaching the maximum value (2.69+/-0.69 microg cm(-2)h(-1)) at 70% (v/v) ethanol in water, and then decreasing with further increases in the ethanol volume fraction. However, in the skin permeation study with testosterone esters saturated in 70% (v/v) ethanol in water system, testosterone esters were hardly detected in the receptor solution, probably due to the rapid degradation to testosterone during the skin permeation process. Moreover, a parabolic relationship was observed between the permeation rate of testosterone and the log P values of ester derivatives. Maximum flux was achieved at a log P value of around 3 which corresponded to that of testosterone (log P = 3.4). The results showed that the skin permeation rate of testosterone and its ester derivatives was maximized when these compounds were saturated in a 70% ethanolic solution. It was also found that a log P value of around 3 is suitable for the skin permeation of testosterone related compounds.     

Effect of hydrophobic permeation enhancers on the release and skin permeation kinetics from matrix type transdermal drug delivery system of ketotifen fumarate

Ketotifen fumarate is effective in low doses in the treatment of bronchial asthma particularly of allergic origin. However, it is substantially metabolized in the liver when administered orally. Hence transdermal patches of combination of ethylcellulose/polyvinylpyrrolidone and Eudragits RS 100/RL 100 were prepared and their drug release kinetics and skin permeation profiles were evaluated. However, the skin permeation profiles were found to be low and subtherapeutic. Hence three hydrophobic biocompatible substances, viz, isopropyl myristate, isopropyl palmitate and linoleic acid and also combination of isopropyl myristate and linoleic acid were used as permeation enhancers in the film. It was found that isopropyl myristate and linoleic acid combination and isopropyl myristate alone produced promising results compared to isopropyl palmitate and linoleic acid.     

Design and Evaluation of a Monolithic Drug-in-Adhesive Patch for Testosterone Based on Styrene–Isoprene–Styrene Block Copolymer

The purpose of the present study was to design and evaluate a monolithic drug-in-adhesive patch with a novel pressure-sensitive adhesive (PSA) matrix based on styrene–isoprene-styrene (SIS) block copolymer. Testosterone was selected as the model drug. The orthogonal array design for ternary mixtures was employed to optimize the amounts of SIS, C-5 hydrocarbon resin, and liquid paraffin. The drug release percentage, water vapor permeability, adhesive properties were chosen as response variables. The patch formulation was optimized by investigating the effects of the drug loading capacity, the type, and amount of permeation enhancer on the adhesive properties and skin permeation. The compositions of the optimal matrix were: 120 g of SIS copolymer, 120 g of C-5 hydrocarbon resin, 60 g of liquid paraffin. An optimized formulation with maximum skin permeation and acceptable adhesive properties was developed incorporating 2% testosterone and 6% isopropyl myristate. No significant differences for in vitro release, skin permeation, and in vivo absorption were observed between the optimal formulation and Testopatch®. The stability evaluation showed that the patches were stable at 25°C/60% relative humidity for 6 months. The result indicated that SIS copolymer was a suitable and compatible polymer for the development of PSA. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2221–2234, 2013     

介质和有机酸对来曲唑体外经皮透过性的影响(英文)

采用水平双室扩散池,以离体鼠皮为透过屏障,考察介质和有机酸对来曲唑体外经皮透过性的影响。在肉豆蔻酸异丙酯(IPM)中加入乙醇后能明显地增加来曲唑的经皮透过量,尤其以含有20%(w/w)乙醇的IPM混合溶液促进作用最为显著。在此溶液系统中,加入的有机酸和来曲唑形成了复合物明显地增加了来曲唑的经皮透过性。由于加入有机酸的结构不同,因此其对来曲唑经皮通透具有不同的促进作用。本实验的结果表明在含有20%乙醇的IPM溶液系统中加入有机酸是促进来曲唑经皮透过性更为有效的方法。