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     

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.     

左金微乳凝胶与水凝胶体外释放和经皮渗透特性的研究

目的:研究、比较左金微乳凝胶、水凝胶体外释放和经皮渗透特性,探讨微乳凝胶对药物释放及透皮性能的影响。方法:采用改良Franz扩散池,以凝胶中小檗碱、巴马汀、吴茱萸碱、吴茱萸次碱等4种生物碱为评价指标,采用HPLC方法测定接收液中上述4个成分含量。结果:吴茱萸次碱的体外释放速率水凝胶高于微乳凝胶,而吴茱萸碱释放速率微乳凝胶高于水凝胶,其余两个成分体外释放无明显差异。微乳凝胶中吴茱萸碱、巴马汀、小檗碱的经皮渗透速率比水凝胶分别提高了10倍、36倍、26倍,提示微乳凝胶具有明显的经皮渗透优势。两种凝胶中四个指标成分的体外释放和经皮渗透行为均符合零级方程。吴茱萸次碱较为特殊,其在水凝胶中透皮速率比微乳凝胶高1.6倍。结论:微乳凝胶能显著增强药物成分的经皮渗透能力。     

Addition of Transdermal or Inhaled Long-Acting β 2-Agonists in Adult Asthmatic Patients Treated with Inhaled Corticosteroids: Switchover Study from Tulobuterol Patch to Salmeterol Dry Powder Inhaler

Sixty-four patients with persistent asthma receiving 200 to 800 μ g of fluticasone propionate daily were enrolled in this switchover study. The patients applied a tulobuterol patch 2 mg every 24 hours for 4 weeks followed by inhalation of salmeterol 100 μ g bid for 4 weeks. The mean values for morning and evening peak expiratory flow improved significantly compared with baseline during the 4 weeks of tulobuterol patch treatment. Further improvement was seen on switching to salmeterol treatment, which was significant even in the first week, and continued until the final week of the study. Use of salmeterol alone resulted in a significant increase in the percentage of forced expiratory volume in 1 second %FEV1 from baseline, with 51% of patients feeling that the treatment was effective (vs. 37% on tulobuterol). These data suggest that salmeterol can achieve better control in asthmatic patients after switching from using tulobuterol patches.     

Rotigotine transdermal patch in early Parkinson's disease: a randomized, double-blind, controlled study versus placebo and ropinirole.

Rotigotine is a new, non-ergot dopamine agonist formulated in a transdermal delivery system. The present study was to investigate the efficacy and safety of the rotigotine transdermal patch in the treatment of early Parkinson's disease. Patients (n = 561) were randomized to rotigotine, ropinirole, or placebo. The titration period was up to 13 weeks, and there was a minimum dose-maintenance period of 24 weeks for ropinirole and 33 weeks for rotigotine. The primary endpoint was the proportion of patients with a minimum of 20% decrease in the combined Unified Parkinson's Disease Rating Scale Part II and Part III scores. The responder rate in the rotigotine group was significantly higher than in the placebo group (52% vs. 30%, P < 0.0001). Transdermal rotigotine at doses < or =8 mg/24 h did not show noninferiority to ropinirole at doses < or =24 mg/day. In a post-hoc subgroup analysis, rotigotine < or =8 mg/24 hours had a similar efficacy to ropinirole at doses < or =12 mg/day. The rotigotine transdermal patch was well tolerated. The most common adverse events were application-site reactions, nausea, and somnolence. Application-site reactions were predominantly mild or moderate in intensity. In conclusion, the rotigotine transdermal patch represents an effective and safe option for the treatment of patients with early Parkinson's disease.     

Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -