复方硝酸咪康唑氢化可的松软膏的体外透皮吸收研究

目的建立HPLC法用以研究复方硝酸咪康唑氢化可的松软膏的透皮吸收。方法采用HPLC法同时测定硝酸咪康唑和氢化可的松的质量浓度,并对该方法进行验证。以Franz扩散池和体外小鼠皮进行体外渗透实验,评价制剂的体外透皮吸收效果。结果氢化可的松和硝酸咪康唑分别在0.10~12.51(r=0.999 5)和0.20~25.12mg·L-1(r=0.999 6)范围内线性关系良好;药物溶液室温放置72h稳定。软膏释药率在0.1%~10%范围内,氢化可的松与硝酸咪康唑的回收率分别为100.4%与100.1%。确定处方制剂与参比制剂36h内体外透皮吸收差异无统计学意义。结论 HPLC法可用以研究复方咪康唑氢化可的松软膏的体外透皮吸收。     

莫匹罗星软膏的质量评价

目的评价国内不同企业生产的莫匹罗星软膏的质量。方法按照现行质量标准检验结合探索性研究,包括对产品的有关物质、聚乙二醇含量、黏度、粒度、酸碱度、透皮吸收等的考察,综合评价产品质量及现行质量标准对产品质量的可控性。结果抽取的127批样品,按国家标准检验合格率为100.0%。探索性研究结果表明,酸碱度测定结果均近中性;6个生产企业样品杂质种类和水平相近;但黏度、粒度、透皮吸收等存在差异。结论目前莫匹罗星软膏总体质量较好;现行标准需进一步完善,建议增/修订有关物质检测方法;建议企业对莫匹罗星软膏剂的处方、工艺进行再评价。     

建立超高效液相色谱法测定莫匹罗星软膏含量

目的:建立莫匹罗星软膏含量测定超高效液相色谱法,提高检测效率。方法:采用超高效液相色谱法(Ultra performance liquid chromatography, UPLC),色谱柱为ACQUITY UPLC BEH C₁₈(2.1 mm×100 mm, 1.7μm);流动相为0.01 mol·L^-1磷酸二氢钠(1 mol·L^-1 NaOH调节pH至6.3)-乙腈(75∶25);检测波长为230 nm;流速为0.4 mL·min^-1。结果:建立了莫匹罗星软膏含量测定超高效液相色谱方法,此方法精密度好,准确度高,其线性范围为0.01～1 mg·mL^-1,R²为0.999 6。结论:相比于高效液相色谱(High Performance Liquid Chromatography, HPLC)法,本文所提方法更便捷高效,可有效地控制莫匹罗星软膏含量。     

复方成膜凝胶剂的体外透皮研究

摘 要 目的：制备复方成膜凝胶剂并对其进行体外释放和透皮吸收研究。方法: 采用新型成膜材料,制得复方成膜凝胶剂,对其进行体外释放度测定,采用Franz扩散池研究复方成膜凝胶剂的透皮吸收行为。结果: 复方成膜凝胶剂主要药效成分莫匹罗星和达克罗宁的体外释放度分别为81.34%和88.46%;透皮累积释放量分别为(192.73±0.45) μg·cm-2和(103.58±0.66) μg·cm-2;皮肤滞留量分别为(419.81±1.48) μg·cm-2和(212.07±1.81) μg·cm-2。结论: 药物释放接近完全,在透皮吸收试验中,约30.26%的莫匹罗星和32.53%的达克罗宁可以透过皮肤,约65.91%的莫匹罗星和66.59%的达克罗宁滞留于皮肤中,药物在局部发挥抑菌作用的同时还可以进入机体起到促进伤口愈合和镇痛的功效。     

HPLC测定他克莫司软膏体外透皮吸收

目的 建立规格为0.03%的他克莫司软膏体外透皮接收液中药物的HPLC测定方法,研究0.03%他克莫司软膏的体外透皮量。方法 采用Diamonsil C18色谱柱（250 mm×4.6 mm,5μm）;流动相：乙腈-水-磷酸（700∶300∶1）;流速：1.0 mL.min 1;检测波长：215 nm。体外透皮实验采用改良的Franz直立式扩散池,透皮屏障采用实验用离体乳猪皮。将自制软膏与市售软膏的透皮结果进行对比分析,分别在设定的不同时间点取样测定透皮接收液中他克莫司的浓度,计算累积透皮量。结果 他克莫司的标准曲线方程为A=16 310.263C＋3 629.783（r=0.999 97）,线性范围为2.088-20.88μg.mL 1,平均回收率为99.10%。累积透皮量与时间呈良好的线性关系,自制软膏与市售软膏的透皮结果无显著性差异。结论 该检测方法操作简便,快速准确,是考察他克莫司软膏体外透皮性能的理想方法。     

0.1%他克莫司软膏的体外透皮吸收研究

目的：建立0.1%他克莫司软膏体外透皮接收液中药物的HPLC测定方法,研究0.1%他克莫司软膏的体外透皮量。方法：采用Kromasil 100-5 C18色谱柱（250mm×4.6mm,5μm）;流动相：乙腈-水-磷酸（690∶310∶1）;流速：1.0ml/min;检测波长：215nm。体外透皮实验采用自制改良的Franz直立式扩散池,使用实验用离体乳猪皮作为透皮屏障。将自制凝胶与市售凝胶的透皮结果进行对比分析,分别在设定的1h、2h、4h、6h、8h、12h时间点取样测定透皮接收液中他克莫司的浓度,计算累积透皮量。结果：他克莫司的标准曲线方程为A=17408.1203×C＋555.4604（r=0.9995）,线性范围为2.036～20.36μg/ml,平均回收率为99.15%。结果表明,累积透皮量与时间呈现良好的线性关系,自制乳膏与市售乳膏的透皮结果无显著性差异（P〉0.05）。结论：本检测方法操作简便,快速准确,是考察他克莫司软膏的体外透皮性能比较理想的方法。     

局部氧疗配合莫匹罗星软膏治疗婴儿尿布皮炎的疗效分析

目的观察局部氧疗配合外涂莫匹罗星软膏治疗婴儿尿布皮炎的效果。方法将60例尿布皮炎患儿随机分为观察组和对照组,两组患儿经一般护理后,对照组直接外涂莫匹罗星软膏,而观察组经一般护理后,先用氧气吹皮损部位后再外涂莫匹罗星软膏,1个疗程后观察两组疗效。结果观察组的总有效率为96.7%,对照组的总有效率为76.7%,2组疗效比较差异有统计学意义(P<0.05)。结论局部氧疗配合莫匹罗星软膏治疗婴儿尿布皮炎,能加快红肿消退,促进炎症吸收,加速创面愈合,从而缩短病程。     

岩藻黄质水凝胶透皮贴剂体外释放度及透皮率的测定

目的研究不同吸收促进剂对岩藻黄质水凝胶透皮贴剂体外释放度及透皮率的影响。方法采用HPLC法测定岩藻黄,Ultimate色谱柱(250mm×4.6mm,5μm),流动相为乙腈-水(70%~100%、100%~100%、100%~70%),检测波长为449nm,流速为1.0mL/min,进样量20μL。采用Franz透皮扩散池,以离体小鼠腹部皮肤为透皮屏障,3%薄荷醇、3%氮酮、1%,3%,5%油酸为吸收促进剂,测定岩藻黄质透皮贴剂透皮率,考察各类促渗剂对岩藻黄质经皮吸收的影响。采用《中国药典》释放度测定法第三法测定岩藻黄质水凝胶透皮贴剂体外释放度,释放介质为60%乙醇–生理盐水。结果各类吸收促进剂对岩藻黄质水凝胶透皮贴剂的经皮渗透均有一定的促进作用,以5%油酸最为显著。岩藻黄质水凝胶透皮贴剂的体外释放行为比较符合零级方程,J=11.785μg·cm-2·h-1。结论以亲水性高分子材料为基质,5%油酸为吸收促进剂,制成岩藻黄质水凝胶贴剂,为其药代动力学和临床研究研究提供依据。     

不同透皮吸收促进剂对左旋肉碱透皮特性的影响

目的:选择适宜的透皮吸收促进剂增加左旋肉碱的透皮百分率。方法:使用改良Franz体外释药装置,用RP-HPLC法检测接收液中左旋肉碱的浓度,计算药物的透皮累积释放量,采用滞留时间法求算经皮渗透相关系数,考察不同用量的丙二醇、尿素、氮酮对左旋肉碱的促透作用。结果:左旋肉碱的溶液在体外透皮释放试验中有透皮吸收。不同种类及不同用量的吸收促进剂对左旋肉碱的促透作用不同,且随着透皮时间的延长,促透量显著增加。3种透皮吸收促进剂中尿素和丙二醇的促透作用较好,氮酮的促透作用稍差。结论:透皮吸收促进剂能够增加左旋肉碱的透皮百分率,其中2.5%的丙二醇促透作用最强。     

莫匹罗星软膏在贮存过程中的主要降解产物研究

目的：对莫匹罗星软膏在贮藏过程中的主要降解产物进行研究。方法：取样品分别置于30℃、40℃恒湿箱中,放置6个月,分别于0、1、2、3、6个月取样进行有关物质检查。色谱条件：色谱柱为C18;流动相A为0.05mol/L磷酸二氢钠溶液（pH6.6）-乙腈（80∶20）,流动相B为乙腈;柱温为25℃;流速为1.0ml/min;检测波长为229nm;进样量为20μl。结果：样品的莫匹罗星杂质D[1]和杂质E[1]含量明显升高,其他杂质含量无明显变化;结论：莫匹罗星软膏在贮存过程中的主要降解产物为杂质D和杂质E。     

两种渗透促进剂对药物透皮吸收的作用

本文主要研究了两种渗透促进剂氮酮和卖泽对亲脂性药物硝苯吡啶、炎痛喜康和亲水性药物扑热息痛、苯呋心安通过小鼠皮肤渗透性的影响。将药物与促进剂一起制成油性软膏、选择适宜的释放液进行体外释放试验,从而计算出药物的稳定状态流量(J),以说明药物渗透性的大小。结果表明:两种促进剂都能增加药物的皮肤渗透性,促进剂浓度的选择由具体药物确定。     

Effects of glycerol on the in vitro percutaneous absorption of all-trans retinoic acid

The nature of the receptor solution plays an important role in in vitro percutaneous absorption of highly lipophilic compounds having limited solubility. In vitro permeation studies of a lipophilic compound, all-trans retinoic acid (RA), through the rat dorsal skin were performed with the presence of glycerol (0-20% v/v) in the receptor solution, and the results were compared with those with the presence of albumin (4%). The results showed that an addition of glycerol (20%) into the receptor solution significantly increased the permeation rate of RA through the rat dorsal skin (0.0068 +/- 0.0041 vs. 0.0014 +/- 0.0010 microg/cm2/hr). It was also found that RA tends to accumulate in the lipophilic layer, and its log P value between the epidermis and the receptor solution significantly decreased with the presence of glycerol (20%) (1.48 +/- 0.14 vs. 2.45 +/- 0.21). An addition of glycerol, an osmotherapeutic agent, in the physiological receptor solution seemed to enhance the percutaneous absorption of RA by affecting the partition coefficient of RA.     

In vitro skin absorption and drug release - a comparison of six commercial prednicarbate preparations for topical use.

Reconstructed human epidermis is a useful tool for in vitro skin absorption studies of chemical compounds. If this may hold true also for topical dermatics, we investigated the glucocorticoid prednicarbate applied by two sets (innovator and generic) of cream, ointment and fatty ointment using the commercially available EpiDerm model. Moreover, stability and local tolerability of the preparations as well as drug release were studied, to estimate an influence on prednicarbate absorption and metabolism. While release ranked in the order cream相似文献   

Effects of Glycerol on the In Vitro Percutaneous Absorption of All-Trans Retinoic Acid

The nature of the receptor solution plays an important role in in vitro percutaneous absorption of highly lipophilic compounds having limited solubility. In vitro permeation studies of a lipophilic compound, all-trans retinoic acid (RA), through the rat dorsal skin were performed with the presence of glycerol (0–20% v/v) in the receptor solution, and the results were compared with those with the presence of albumin (4%). The results showed that an addition of glycerol (20%) into the receptor solution significantly increased the permeation rate of RA through the rat dorsal skin (0.0068±0.0041 vs. 0.0014±0.0010 μg/cm²/hr). It was also found that RA tends to accumulate in the lipophilic layer, and its log P value between the epidermis and the receptor solution significantly decreased with the presence of glycerol (20%) (1.48±0.14 vs. 2.45±0.21). An addition of glycerol, an osmotherapeutic agent, in the physiological receptor solution seemed to enhance the percutaneous absorption of RA by affecting the partition coefficient of RA.     

两种卡泊三醇软膏的体外经皮吸收比较

目的:比较两种不同厂家生产的卡泊三醇软膏(样品A和样品B)的体外透皮吸收情况,并与卡泊三醇搽剂进行比较。方法:采用改良Franz扩散池,小型猪离体皮片分别涂样品A、B和卡泊三醇搽剂(以主药计均为5μg),于给药后2、4、6、8、10、12 h吸取接收液,药物接触的皮片用稀释剂提取。采用高效液相色谱法测定接收液和提取液中卡泊三醇的含量,计算卡泊三醇的皮片保留量、透过百分率和吸收百分率。结果:样品A、B和卡泊三醇搽剂中卡泊三醇在皮片内的保留量分别为(1 519.07±655.88)、(605.83±235.33)、(2 897.29±723.89)ng/g;吸收百分率平均值分别为3.21%、1.25%、6.69%,三者比较差异具有统计学意义(P<0.05);透过百分率均低于0.36%。结论:样品A、B的经皮行为具有明显差异,其中样品A的生物利用度较好。     

Influence of limonene and laurocapram on percutaneous absorption of nonsteroidal anti-inflammatory drugs.

The promoting effect of cyclic monoterpenes, 1% limonene (CAS 5989-27-5) and 1% cineole (CAS 470-82-6), on percutaneous absorption of nonsteroidal anti-inflammatory drugs was investigated in the rats. Compared with 1% laurocapram, drug absorption from the gel ointments was significantly more enhanced by addition of 1% limonene, while without any enhancer only ibuprofen penetrated across the skin in the limited amount. When using formulation with propylene glycol or 50% propylene glycolethanol solution, instead of carboxyvinyl polymer gel, percutaneous absorption significantly decreased and neither limonene nor cineole or laurocapram were capale to promote percutaneous absorption of flufenamic acid to sufficient serum level. Cineole and limonene were also evaluated in permeation experiments in vitro. Enhancement ability of limonene in the gel oinment was approximately 5 times higher comparing with enhancement ratio of cineole, while in 100% propylene glycol enhancement ability of both cyclic monoterpenes was equal. Good correlation was observed between in vivo and in vitro experiments. Evaluation of solubility proved that in the gel ointment simulated as water-ethanol solution were relatively best condition for percutaneous absorption of flufenamic acid when comparing with propylene glycol or 50% propylene glycol-ethanol solution.     

固体脂质纳米粒作为水杨酸经皮给药载体的研究

目的 考察固体脂质纳米粒作为经皮给药载体对水杨酸经皮吸收的促渗透作用.方法 采用薄膜超声法制备水杨酸固体脂质纳米粒,以改良的Franz扩散池考察其体外透皮特性;并与水杨酸软膏剂比较,考察其促渗作用.结果 制备的水杨酸固体脂质纳米粒均匀圆整,包封率为46.4%,体外透皮特性优于普通软膏剂,24 h后皮肤药物累积透过量为654.3 μg/cm2,皮肤中药物残留量为22.99 μg,均分别显署高于软膏剂组(128.0 μg/cm2和0.84 μg,P<0.05).结论 固体脂质纳米粒作为水杨酸经皮给药载体,可有效促进药物透皮吸收和增加药物在皮肤中储留量,而且可延缓药物的释放,从而有效提高药物疗效及患者依从性.