Transdermal Dual-Controlled Delivery of Testosterone and Estradiol: (I) Impact of system Design

A multilaminate-type transdermal drug delivery (m-TDD) system was designed with the objective of delivering testosterone and estradiol simultaneously but at different daily dosage rates. To achieve such a dual-controlled transdermal delivery, skin permeation enhancer and permselective membrane were incorporated into the system. The results demonstrated that skin permeation enhancer, which is incorporated into the testosterone reservoir layer, and permselective membrane, which is added onto the drugreleasing surface of estradiol reservoir layer, can both alter the overall rate of skin permeation for both drugs. The skin permeation enhancer was observed to enhance the skin permeation rate of testosterone, while the permselective membrane was shown to reduce the skin permeation rate of estradiol. The addition of permselective membrane was observed to modify the release kinetics of estradiol from the matrix diffusion-controlled drug delivery to membrane permeation-controlled drug delivery. Other factors which may affect the deliver rate of drug, e.g., the thickness of permselective membrane and loading dose of drugs, were also studied. Furthermore, evaluation of physical stability of this mTDD system demonstrated that the inter-layer migration of drugs is at minimum.     

工质P-v-T 性质(定容法)实验研究中测试仪器的优化匹配

本文根据误差理论的误差等作用分配原则,以及由各物理参数内在联系所确定的误差传递规律,对工质 P-v-T 性质的实验研究中各参数的测量精度要求进行了估算,提出为准确地确定一个状态。必须统一地提出 P、v、T 三个参数的测量精度要求,并合理地配置各参数的测量仪器的精度等级。     

三种堆型核电厂经济性评价

本文分析了核电投资的特点、建立了考虑价格浮动和通货膨胀等因素影响的核电厂建成价和核燃料成本的计算模型。对压水堆、高温气冷堆和快堆三种堆型的经济性进行了研究。结果表明，当高温气冷堆和快堆两种先进堆型实现商用概念设计后，其商业竞争能力可与现有的压水堆相媲美。     

Recent Advances in Noninvasive Systemic Delivery of Pharmaceuticals and Biopharmaceuticals

Many systemically-active Pharmaceuticals and biopharmaceuticals are reportedly subjected to extensive pre-systemic elimination when taken orally.

To circumvent this dilemma in systemic delivery, extensive research efforts have recently been devoted to explore various nonparenteral (noninvasive) routes of administration for enhancing systemic bioavailability of pharmaceuticals and biopharmaceuticals, which have been reportedly subjected to extensive pre-systemic elimination, via the bypassing of hepatogastrointestinal “first-pass” metabolism. Using nicotine, a pharmaceutical, and enkephalin, a biopharmaceutical, the systemic delivery of pharmaceuticals and biopharmaceuticals through the skin and the various absorptive mucosae has been illustrated. The mechanisms and kinetic processes involved for their systemic delivery are explored and various technical issues encountered are discussed in this article.     

Effect of Cationic Surfactants on the Transdermal Permeation of Ionized Indomethacin

In an attempt to enhance the skin permeation rate of ionized indomethacin by ion-pairiig, a group of cationic surfactants were evaluated to determine their potential as counter-ions. Permeation rates through hairless rat skin were measured in vitro. The ion-pairing agents used were all quaternary ammonium compounds. Most enhanced the skin permeation of indomethacin to varying magnitudes and through different mechanisms. Some involved increased drug solubilization in the aqueous vehicle while others demonstrated permeability increase as a function of partitioning. One surfactant did not exert an apparent effect on any of the permeation parameters. Of Arquad^R 12, Arquad^R 16, Cetylpyridinium chloride^R and Benzalkonium chloride^R, only the last surfactant clearly indicated its ability to pair with indomethacin.     

Enhancement of in vitro skin permeation of verapamil

A number of compounds including aliphatic esters, alkanols and amides were investigated for their ability to enhance the in vitro permeation rate of verapamil across hairless mouse skin. While several of them did enhance the permeation rate, the best results were obtained with the lauric acid derivatives. On analysis of the permeation rate data it was found that while most of the compounds increased the solubility of verapamil in skin and hence its partition coefficient from the delivery system, the lauric acid derivatives also increased its diffusivity in skin. Permeation of verapamil from delivery systems containing these lauric derivatives was further investigated through delipidized and stripped skin. It was found that most of these derivatives enhanced the permeation of verapamil across both whole and delipidized skin, indicating that in addition to their action on the skin lipids, they must also have some effect on the proteins in the stratum corneum.     

A New Transmucosal Therapeutic System: Overview of Formulation Development and in Vitro/In Vivo Clinical Performance

A new transmucosal therapeutic system (TmTs) was developed for controlled systemic delivery of drugs, which are labile to hepatic “first-pass” metabolism, through oral mucosa. It consists of a fast-release layer, which provides a rapid release of drug for prompt rise in blood drug concentration to reach the therapeutic level, and a sustained-release layer, which releases the drug continuously for sustained duration to maintain the therapeutic level for up to 12 hrs. The sustained-release layer also contains mucoadhesive composition, so TmTs can be applied on gingival mucosa for continuous transmucosal controlled administration of drugs. Using isosorbide dinitrate (ISDN), a well-known antianginal drug which is known to be subjected to extensive presystemic elimination when taken orally, the systemic bioavailability has been improved by 37 fold in beagle dogs and by almost 5 fold in humans compared to that of marketed oral sustained-release tablet and the plasma concentration profile has also been prolonged to 12 hrs from less than 1 hr for marketed sublingual tablet and spray products in both beagle dogs and in human volunteers. Multi-fractional absorption model has been successfully applied for pharmacokinetic analysis, which demonstrates that the rate-limiting step for the transmucosal systemic delivery is the release of ISDN from the TmTs. Clinical studies performed in the anginal patients for up to one year have demonstrated the therapeutic benefits of this TmTs in achieving a substantial reduction in the frequency of anginal attacks and prolongation in the duration of exercise time.