pH值对富马酸比索洛尔化学稳定性及油水分配系数的影响

目的:研究pH值对富马酸比索洛尔(bisoprolol fumarate,BF)的化学稳定性及油水分配系数(P)的影响,为研制BF的粘膜给药液体制剂奠定基础。方法:采用HPLC法测定BF的浓度;在不同pH值下,分别测定BF在80℃下的降解百分率以及在25℃下正辛醇-水/缓冲液系统中的P值。结果:在所考察pH值范围内,随着pH的增加,BF的降解百分率逐渐减小,在pH大于4.0时,BF的降解速率趋于零。BF在正辛醇-水系统中的P值为0.23;在正辛醇-缓冲液系统中,pH为2.0～7.0范围时,药物的P值均小于1,在pH大于7.0时,P值显著增大。结论:pH值对BF的化学稳定性以及P值均有明显影响。选择适宜的pH值,对研制BF的粘膜给药液体制剂极其重要。     

HPLC-DAD-ESI-MS~n法研究红花注射液中羟基红花黄色素A和脱水红花黄色素B的稳定性及降解过程(英文)

红花是一种常用中药,红花注射液广泛地应用于临床治疗心脑血管疾病。本研究应用HPLC-DAD-ESI-MSn方法研究红花注射液中两种主要物质,羟基红花黄色素A和脱水红花黄色素B的稳定性及降解过程。考察了光照、温度、pH值对二者稳定性的影响。结果表明,羟基红花黄色素A和脱水红花黄色素B在温度大于60°C,pH≤3.0或>7.0时易发生降解且最终降解产物为对羟基桂皮酸,而光照对其影响不大。本研究应用LC-MS对其降解产物及降解过程进行推导,首次描述了两种物质的降解途径。此外ADP诱导的血小板凝集实验结果显示脱水红花黄色素B降解以后会大大降低红花注射液的抗凝活性。建议红花注射液生产及储存过程中应严格控制温度和pH值。     

pH值对盐酸林可霉素输液的影响

目的　考察不同pH条件对盐酸林可霉素输液的影响。方法　分别制备pH值为 6.0 ,6.5 ,7.0的林可霉素输液 ,于低温(4℃ )、高温 (60℃ )及强光照射 (45 0 0lx ,2 5℃ )等条件下考察了各输液的稳定性。HPLC测定了所考察样品的含量及降解产物等。结果　pH为 7.0样品的外观及澄明度度均不合格 ,高温 10d的含量下降 8%左右 ;而 pH为 6.0样品的外观、澄明度及药物含量、色谱降解产物均无明显变化 ;pH6.5样品的考察结果介于两者之间。HPLC含量方法回收率 :(99.8± 0 .8) % ;标准曲线 :Cmg/mL =1.84682 9X - 0 .0 85 5 2 6,r =0 .9996;最低检出限 :6ng。 结论　盐酸林可霉素输液的 pH为 6.0时 ,样品在强光、高温、低温等条件下均稳定。因此 ,输液的pH上限以 6.0为宜。     

pH值对盐酸吡硫醇水溶液稳定的影响

目的考察pH值对盐酸吡硫醇水溶液稳定性的影响.方法用恒温加速试验法,测定不同温度下不同pH值时盐酸吡硫醇降解的速率常数,得到不同pH值时的降解活化能及不同温度下的最稳定pH值.结果在不同温度下,当pH2时,盐酸吡硫醇水溶液相对最稳定;随着pH值升高,水溶液稳定性迅速降低.结论适当调整溶液的pH值可以显著改善盐酸吡硫醇的化学稳定性,为其制剂学研究提供了部分依据.     

pH值对右旋布洛芬体外透皮性能的影响研究

目的:研究pH值对右旋布洛芬(DI)体外透皮性能的影响,为其透皮给药制剂的开发提供实验依据。方法:建立DI的高效液相色谱分析方法,测定其在水和不同pH的磷酸盐缓冲液(PBS)中的平衡溶解度;用摇瓶法测定DI的正辛醇溶液在正辛醇饱和蒸馏水与不同pH的PBS中的表观油水分配系数;以稳态渗透速率(Js)和渗透系数(Ps)为评价指标,检测不同pH的PBS对DI体外透皮性能的影响。结果:32℃时,DI在水中难溶;在pH7.4的PBS中平衡溶解度、Js、Ps均最大,表观油水分配系数极小,分别为5421.6μg·mL-1、339.97μg·cm-2·h-1、0.063cm·h-1、0.17。结论:pH值对DI体外透皮性能有很大影响,pH7.4时DI有较高的溶解度、脂溶性及较理想的皮肤通透性。     

TiO_2光催化降解水中盐酸左氧氟沙星

目的以锐钛型TiO_2为光催化剂,研究其对水中盐酸左氧氟沙星的光催化降解性能。方法采用单因素实验方法考察溶液pH值、TiO_2用量、药物初始浓度和金属离子对盐酸左氧氟沙星光催化降解的影响规律。结果当TiO_2用量为4.0 g·L~(-1)、药物初始质量浓度为6 mg·L~(-1),pH=7.0,光照反应10 min时,盐酸左氧氟沙星的降解率在96%以上;溶液中的Na~+、Zn~(2+)、Fe~(3+)对盐酸左氧氟沙星降解具有抑制作用,抑制作用从高到低的顺序为Fe~(3+)、Zn~(2+)、Na~+。结论锐钛型TiO_2能够有效地降解水中的盐酸左氧氟沙星药物。     

pH值对盐酸吡硫醇水溶液稳定性的影响

目的:考察pH值对盐酸吡硫醇水溶液稳定性的影响。方法:用恒温加速试验法,测定不同温度下不同pH值时盐酸吡硫醇降解的速率常数,得到不同pH值时的降解活化能及不同温度下的最稳定pH值。结果:在不同温度下,当pH2时,盐酸吡硫醇水溶液相对最稳定;随着pH值升高,水溶液稳定性迅速降低。结论:适当调整溶液的pH值可以显著改善盐酸吡硫醇的化学稳定性,为其制剂学研究提供了部分依据。     

pH对甘草次酸经皮渗透性的影响

目的考察介质的pH对甘草次酸经皮渗透性的影响。方法采用HPLC法测定甘草次酸在不同pH介质中的饱和溶解度,采用摇瓶法测定其在不同pH正辛醇/PBS缓冲液中的表观油水分配系数,采用体外Franz扩散池法考察不同pH的甘草次酸饱和溶液在离体小鼠皮上的经皮渗透性。结果 pH5.0～10.8时,甘草次酸饱和溶液的稳态透皮速率随pH升高而增大,而表观渗透系数随pH升高而减小。结论甘草次酸在介质中饱和时,可通过调节pH来改善甘草次酸的稳态透皮速率。     

苦参碱微乳水凝胶的质量评价及透皮研究

摘 要 目的：考察苦参碱微乳水凝胶（MBH）的质量及其透皮性能,为苦参碱制剂的研发提供依据。 方法: 在4℃条件下放置3个月,考察MBH的稳定性,主要观察MBH粒子外观、黏度、pH、苦参碱含量等指标的变化。以小鼠离体皮肤为模型,采用双室渗透扩散装置考察MBH的经皮渗透情况。以家兔为实验对象,考察MBH对正常皮肤和受损皮肤的刺激性。结果: 苦MBH在4℃条件下放置3个月后,其粒子外观、黏度、pH及苦参碱含量未发生明显变化。体外透皮实验表明,MBH对小鼠皮肤的渗透速率良好,单次或多次给药后无皮肤刺激性。结论:MBH具有良好的稳定性,透皮速率高,皮肤刺激性小,是一个具有开发应用前景的苦参碱经皮给药体系。     

顺铂水溶液稳定性研究

建立了高效液相色谱法 (HPLC)测定顺铂水溶液的稳定性 ,考察了pH值、氯化钠浓度、温度及光照对顺铂水溶液稳定性的影响 .由HPLC图谱表明 ,顺铂在不同 pH值水溶液中 ,产生不同的降解产物 ,说明其降解机制不同 .pH值在 4 0～ 6 0时 ,顺铂水溶液稳定性较好 ,氯化钠浓度在0 9%～ 1 5 %范围内顺铂较稳定 ,0 9%以下稳定性较差 ,顺铂水溶液对光十分敏感 .     

Elastic liposomes mediated transdermal delivery of an anti-hypertensive agent: propranolol hydrochloride

One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present investigation ultradeformable lipid vesicles, that is, elastic liposomes were prepared incorporating propranolol hydrochloride for enhanced transdermal delivery. Elastic liposomes bearing propranolol hydrochloride were prepared by conventional rotary evaporation method and characterized for various parameters including vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity, and in vitro drug release. In vitro flux, enhancement ratio (ER), and release pattern of propranolol hydrochloride were calculated for transdermal delivery. In vivo study conducted on male albino rats (Sprague Dawley) was also taken as a measure of performance of elastic liposomal, liposomal, and plain drug solution. The better permeation through the skin was confirmed by confocal laser scanning microscopy (CLSM). Results indicate that the elastic liposomal formulation for transdermal delivery of propranolol hydrochloride provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared to liposomes.     

Transdermal iontophoresis of insulin. Part 1: A study on the issues associated with the use of platinum electrodes on rat skin

We have studied the issues associated with the use of platinum electrodes for transdermal iontophoretic delivery of peptides, using insulin as a model peptide. Insulin permeation was studied using full-thickness rat skin by varying the donor solution pH as a function of electrode polarity. The stability of insulin under the iontophoretic conditions was studied using TLC, SDS-polyacrylamide gel electrophoresis and HPLC. Large pH shifts were observed during anodal iontophoresis (AI), when the donor solution pH was above the isoelectric point of insulin and in cathodal iontophoresis (CI), when the donor solution pH was below the isoelectric point of insulin. The direction and magnitude of electroosmotic flow was influenced by pH of the donor solution and the electrode polarity. On the other hand, the buffer used to maintain the pH governed the contribution of electrorepulsion to the overall transport of insulin. Electrochemical degradation of insulin was significant during AI at pH 7.4. Among the pH investigated, AI of insulin at pH 3.6 and CI at pH 8.35 were better, as the pH shift was relatively less and electrochemically more stable during iontophoresis as compared with other pH. In summary, the pH shift caused by platinum electrodes had a significant influence on the permeation and stability of insulin.     

胰岛素溶液化学稳定性研究

本文用反相高效液相色谱法(RP-HPLC)和高效液相凝胶层析法(GF-HPLC)研究了pH值对胰岛素溶液化学稳定性的影响。稳定性实验采用经典恒温法。实验结果表明pH值是影响胰岛素溶液化学稳定性的重要因素,在酸性溶液中降解反应速率随pH值的降低而增大;而在碱性溶液中则随pH值的降低而减小,即溶液pH值接近胰岛素等电点时其稳定性最好。胰岛素溶液加热降解反应规律符合一级动力学方程。     

VBE-1平衡溶解度和表观油水分配系数的测定及其酸碱稳定性的考察

目的：测定VBE-1的平衡溶解度和表观油水分配系数,并考察其酸碱稳定性,为药物的制剂设计提供实验依据。方法：采用平衡法和摇瓶法测定VBE-1在不同溶剂中的平衡溶解度以及在正辛醇-水/缓冲溶液中的表观油水分配系数,采用高效液相色谱法测定两者的浓度,并用紫外分光光度法考察VBE-1的酸碱稳定性。结果：VBE-1在PEG-400中的溶解度较大,为（677.47±48.09）g·L^-1。在pH4.0~8.0范围内,pH对VBE-1的表观油水分配系数有影响,表现出表观油水分配系数随着pH升高而降低的趋势。pH的升高会引起VBE-1颜色的改变,但此变化为可逆反应。结论：VBE-1具有一定的透过能力,可满足经皮给药的一般要求,其对pH较敏感,实验过程中应避免在强碱条件下操作。     

月桂酰吲达帕胺的电离常数及分配系数的测定

目的测定月桂酰吲达帕胺的电离常数(pKa)及分配系数。方法采用酸碱滴定法测定各不同体积比的丙酮-水溶液中药物半中和点时的pH值作为药物在该体积比的丙酮-水溶液中的pKa值,再外推至纯水中药物浓度无限稀释时的pKa值;采用HPLC配合摇瓶法测定药物的分配系数。结果月桂酰吲达帕胺的pKa为3.87,lgP值为3.190。结论月桂酰吲达帕胺为弱酸性亲脂性药物。     

Development of mesophasic microreservoir-based transdermal drug delivery system of propranolol

The mesophasic microreservoir comprises lyotrophic liquid crystals. The liquid crystals were prepared of Brij-35, cetosteryl alcohol and propranolol and evaluated for parameters viz. anisotropy, size and size distribution and drug entrapment efficiency. Subsequent to this liquid crystals based transdermal drug delivery system (TDS) was prepared by incorporating liquid crystals in previously prepared matrix based transdermal patch and evaluated for stability studies like temperature, humidity and aging. The system was also studied for tensile strength, moisture content, water vapor transmission, drug content, anisotropy and In vitro drug release studies.     

The effects of dimenhydrinate, cinnarizine and transdermal scopolamine on performance

We assessed the influence of dimenhydrinate, cinnarizine and transdermal scopolamine on the ability to perform simulated naval crew tasks. The effect of single doses of dimenhydrinate, 100 mg, cinnarizine, 50 mg, and one transdermal scopolamine patch on psychomotor performance was evaluated using a double-blind, placebo-controlled, randomized, crossover design in three separate studies. A total of 60 young naval crew (20 for dimenhydrinate, 15 for cinnarizine and 25 for transdermal scopolamine) underwent a battery of computerized and paper and pencil performance tests, and filled out a questionnaire on side-effects and well-being self-assessment. Dimenhydrinate significantly impaired decision reaction time and auditory digit span. Most of the subjects who took dimenhydrinate also reported a subjective decrease in well-being and general performance abilities. Cinnarizine and transdermal scopolamine did not affect performance abilities. Cinnarizine was free of significant side-effects. Dry mouth was the only significant side-effect of transdermal scopolamine. These findings could be explained by the well-known sedative properties of dimenhydrinate and not by a specific effect on any particular cognitive or motor function. Our results suggest that dimenhydrinate, 100 mg, adversely affects psychomotor function, whereas single doses of cinnarizine, 50 mg, and transdermal scopolamine appear to be free of side-effects on performance and seem to be a preferable anti-seasickness drug for use by a naval crew.     

盐酸左旋多巴甲酯水溶液稳定性研究

目的考察pH值对盐酸左旋多巴甲酯水溶液稳定性的影响。方法采用经典恒温加速试验法，考察不同温度下不同pH值对盐酸左旋多巴甲酯稳定性的影响，测定水解速率常数，活化能及最稳定时的pH值。结果在不同温度下，当pH=3．0时，盐酸左旋多巴甲酯水溶液最稳定；当pH〉3时，随着pH值升高，水溶液的稳定性降低。结论适当调整溶液的pH值，可以改善盐酸左旋多巴甲酯的化学稳定性。     

Transdermal Controlled Delivery of Propranolol from a Multilaminate Adhesive Device

The feasibility of transdermal controlled delivery of propranolol was investigated by conducting in vitro skin permeation studies using rabbit pinna (ear) skin. A new multilaminate adhesive device which is capable of releasing propranolol in a controlled fashion over a 24-hr period had been developed and was evaluated transdermally using rabbit pinna skin. Skin permeation of propranolol from the device was found to be controlled by the stratum corneum during the early phase of permeation and then by the adhesive device during steady-state permeation. The rabbit pinna skin was shown to be a good animal model for studying the transdermal permeation of propranolol from the device, when compared to human cadaver skin.     

Optimized transdermal delivery of ketoprofen using pH and hydroxypropyl-beta-cyclodextrin as co-enhancers.

The role of pH and pK(a) of ionizable drugs in transdermal delivery has been well documented by the pH partition hypothesis. Similarly the role of pH in complexation has also been addressed by many studies. Reports contrary to the well believed theory that both molecular encapsulation by hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and transdermal delivery are considered a phenomenon of unionized drug species prompted investigation into the combined effect of pH and HP-beta-CD on transdermal delivery of ketoprofen. In order to optimize the delivery of ketoprofen, solubility studies and permeation studies were conducted in vitro at pH 3.0, 4.5 and 6.0 at various concentrations of cyclodextrin. The stability constants for unionized and ionized drugs were calculated. The solubility of the ionized complex of the drug was 2.5 fold greater than the unionized complex. The flux increased linearly with increasing HP-beta-CD concentration at all the pH values. However, the increase was significant at pH 6.0 where the drug is predominantly in the ionized state. The flux of the ionized drug at 10% w/v HP-beta-CD concentration was enhanced to an order of approximately eight times compared to the intrinsic permeability of the unionized drug. The study shows that at higher pH, HP-beta-CD can be utilized to achieve greater transdermal flux of ketoprofen.