Validation of a Flow-Through Diffusion Cell for Use in Transdermal Research

A flow-through finite-dose diffusion cell has been designed for use in transdermal drug delivery research. The diffusion cell consists of an upper donor chamber and a lower receiver compartment through which a continuous supply of fresh solvent flows. The flow is directed to an automatic fraction collector. To validate the flow-through cell, its performance was compared directly against that of a conventional single-reservoir Franz cell. Homologous alkyl p-aminobenzoates were diffused through dimethylpolysiloxane membranes, and permeability coefficients increased with increasing chain length, reaching a plateau at the butyrate ester for both types of cells. This behavior suggests a shift from membrane-controlled diffusion to boundary layer control. Permeation of the butyrate and valerate compounds was significantly faster when the flow-through cell was used, suggesting that better mixing is obtained through the flow-through cell design. Considering the advantages offered in terms of time and labor saved through its use, the flow-through cell with automatic fraction collector appears to be a viable alternative to the conventional Franz cell.     

两性霉素B微乳的制备及体外经皮渗透研究

 目的制备水包油型两性霉素B微乳,并对其进行体外经皮渗透性能考察。方法用相转变温度法制备两性霉素B微乳,用光散射粒度仪测定微乳的粒径,电子透射电镜观察微乳的形态。用药物渗透扩散仪进行两性霉素B透皮吸收研究,高效液相色谱法测定两性霉素B含量。结果用相转变温度法制备了Tween80和异丙醇重量比为1∶1,IPM和混合表面活性剂之比为1∶9,水含量64.6%,载药量为0.247%的两性霉素B微乳。所制微乳符合微乳特征,调节pH值有助于两性霉素B由分散介质向微乳表面转移。水性月桂氮酮对两性霉素B的促渗效果最好,pH值为5.12,月桂氮酮浓度为1%时,两性霉素B微乳经离体兔皮的JS为4.627μg·cm^-2·h^-1,经离体大鼠皮肤的JS为4.484μg·cm^-2·h^-1。结论开发微乳透皮给药制剂有望提高两性霉素B的疗效,降低其毒副作用。     

银杏内酯B柔性纳米脂质体的制备及体外透皮研究

目的：制备银杏内酯B(GB)柔性纳米脂质体，并对其体外透皮规律进行研究。方法：采用薄膜分散法制备银杏内酯B柔性纳米脂质体，并对其形态及粒径大小进行分析；采用改良的 Franz 扩散池进行体外透皮吸收试验，比较银杏内酯B醇溶液、银杏内酯B柔性纳米脂质体及普通银杏内酯B纳米脂质体的经皮累积渗透量及渗透速率。结果：此方法制得的脂质体平均包封率为(89.52±1.76)%，平均粒径为(208.3±25.49) nm，Zata电位为-49.2 mV。柔性纳米脂质体8 h的累积透过量为189.97 μg·cm^-2，8 h的渗透速率为23.75 μg·cm^-2·h^-1。结论：柔性纳米脂质体包封率较高，稳定性良好，可显著促进银杏内酯B的透皮吸收。     

中药透皮吸收促进剂的研究进展

中药透皮吸收促进剂具有起效快、效果好、副作用小、无污染等优点,总结近年来常用中药透皮吸收促进剂的研究进展,中药透皮吸收促进剂主要包括单一中药透皮吸收促进剂和含中药PE多元透皮吸收促进剂,并对存在的问题及今后的研究前景进行了思考和展望。     

Mechanisms of tolerance during treatment with nitroglycerin patches for 24 h

Objective: We examined the relationship between tolerance development, counterregulatory responses and arterial vasodilating effects evaluated by digital pulse plethysmography. Methods: Twenty patients with stable angina pectoris were exercise tested before, after 2 and after 24 h of open nitrate patch treatment. Results: The effects observed after 2 h of treatment on exercise duration, ST-segment depression, blood pressure and heart rate were lost in most individuals after 24 h. In contrast, the effects on the arterial pulse curves persisted after 24 h, with a mean change from baseline of 29%, compared to 33% at 2 h. After 24 h, a significant decrease in haematocrit and an increase in body weight were observed. The haematocrit changes correlated with the loss of clinical efficacy (r =0.57 for ST-segment depression, and r =0.54 for exercise duration). Conclusion: Clinical nitrate tolerance may be observed despite maintenance of the arterial vasodilating effects, and tolerance is more related to plasma volume expansion as a counterregulatory mechanism. Received: 28 February 1996/Accepted in revised form: 5 July 1996     

Calculation of Hydrolytic Rate Constants of Poly(ortho ester)s from Molecular Weights Determined by Gel Permeation Chromatography

Purpose. To obtained rate constants from weight-averaged (M_w) or z-averaged (M_z) molecular weights for polymers of Schule-Flory distribution and undergoing random scission. These constants were compared with those obtained by parallel ¹HNMR studies. Methods. The hydrolysis of two poly(ortho ester)s were followed by ¹HNMR and gel permeation chromatography (GPC). Results. Equations to convert number-averaged (M_n), M_w and M_z into fraction of backbone remaining (f_c) were derived. First-order hydrolytic rate constants of two poly(ortho ester)s; DETOSU-HD and DETOSU-CDM were calculated using these relationships. The rate constants calculated from ¹HNMR, M_z and M_w were 0.215, 0.218 and 0.182 hr^–1, respectively, for DETOSU-CDM and 0.152, 0.086 and 0.038 hr^–l for DETOSU-HD. The large discrepancy in the rates determined by ¹HNMR and GPC in the latter case was attributed to that the detector response (refractive index) of the monomers was lower than that of the high molecular weight polymer. The difference is small in the case of DETOSU-CDM, and the rates calculated from GPC data were comparable or nearly identical to that obtained from ¹HNMR data. Conclusions. Although GPC can yield rapid and valuable kinetic data for the degradation of biodegradable polymers, the system, however, must be carefully calibrated to account for the variations in Mark-Houwink coefficients and in the response of the mass detector between the high and low MW polymers.     

酵母抽提物超滤制备海藻糖工艺条件的优化

利用响应面分析法对影响酵母抽提液中总氮截留率和海藻糖透过率的主要因素进行分析,优化超滤工艺,得到最佳超滤条件:料液质量浓度10 g／dL,料液温度42℃,操作压力0.31MPa,在最佳超滤条件下得到酵母抽提物蛋白质截留率96.5%,海藻糖透过率94.8%,所得RSA图可直观地反映各因素与蛋白氮截留率和海藻糖透过率的关系.     

Cyclic hormonal replacement therapy after the menopause: Transdermal versus oral treatment

Summary In an open, randomized, comparative, between-patient trial, 45 postmenopausal women were treated for 4 months with cyclical transdermal oestradiol 0.05 mg per day or oral conjugated equine oestrogens 0.625 mg per day, in both cases, plus, medroxyprogesterone acetate 10 mg per day on the last 8 days of each cycle. Similar relief from postmenopausal symptoms was obtained with both treatments. Post-treatment histological evaluation of the endometrium did not reveal neoplastic or hyperplastic change in any patient.Early follicular-phase plasma oestradiol levels were observed only after transdermal oestradiol. There was a significant reduction in serum total cholesterol and LDL cholesterol in both treatment groups, with no difference between treatments, whereas serum triglyceride levels were decreased only by transdermal oestradiol. Plasma calcium and phosphorus fell significantly and serum intact parathyroid hormone rose significantly, with no difference between the therapies. No significant changes were observed in clotting factors.Transdermal oestradiol appears to be an effective and safe hormonal replacement therapy, and this route of administration may be responsible for the more useful action of the drug on serum lipids and plasma oestradiol levels.     

An alkylpolyglucoside surfactant as a prospective pharmaceutical excipient for topical formulations: The influence of oil polarity on the colloidal structure and hydrocortisone in vitro/in vivo permeation

There is a growing need for research into new skin- and environment-friendly surfactants. This paper focuses on a natural surfactant of an alkylpolyglucoside type, which can form both thermotropic and lyotropic liquid-crystalline phases. The aim of this study was to relate some physicochemical properties (characterised by polarisation and transmission electron microscopy, thermal analysis and rheology) of the three formulations based on cetearyl glucoside and cetearyl alcohol, to the results of in vitro and in vivo bioavailability of hydrocortisone (HC). The three formulations contained oils of different polarity (medium chain triglycerides: MG, isopropyl myristate: IPM and light liquid paraffin: LP), respectively. In vitro permeation was followed through the artificial skin constructs (ASC), while the parameters measured in vivo were erythema index: EI (using instrumental human skin blanching assay), transepidermal water loss (TEWL) and stratum corneum hydration (SCH). The vehicles based on cetearyl glucoside and cetearyl alcohol showed a complex colloidal structure of lamellar liquid-crystalline and lamellar gel-crystalline type, depending on oil polarity. Rheological profile of the vehicle was directly related to the in vitro profile of the HC permeation. In vivo results suggested that the vehicle with MG retarded the HC permeation, whereas less polar IPM and non-polar LP enhanced it. It is suggested that the enhancement is achieved either by a direct interaction with lipid lamellae of the SC or indirectly by improving skin hydration.

There were no adverse effects during in vivo study, which indicates a good safety profile of this alkylpolyglucoside surfactant.     

聚芳醚砜薄膜的气体透过行为

研究了一系列聚芳醚砜的Ｈ２、ＣＯ２、Ｏ２、Ｎ２和ＣＨ４气体透过性能，讨论了其气体透过的温度依赖性。与双酚Ａ聚砜（ＰＳＦ）相比，几种新型聚芳醚砜的气体透过系数和气体选择系数同时有所提高。通过聚合物的分子链段活动性和自由体积数据系列变化，讨论了气体透过速率与分子结构的关系。