Preparation and evaluation of optimized zolmitriptan niosomal emulgel

Objective: Novel niosomal formulation may be successfully applied to treat a systemic disease such as migraine through transdermal drug delivery system (TDDS), moreover, the treatment of topical diseases such as mycotic infections by targeting and localizing the drug to the stratum corneum. The current study aims to formulate zolmitriptan (Zt) in niosomal vesicles to potentiate its transdermal effect.

Significance: The development of a promising niosomal formulation will push the scaling up of pharmaceutical industry in this field.

Methods: Design- Expert 10 was used to design twelve formulations using Box-Behnken. Zt loaded niosomes were prepared by the thin film hydration method using Span 60(S 60), Span 80(S 80) along with cholesterol(Ch) at three different levels. The optimized formulation (F11) was formulated in Emulgel (1:1 emulsion/gel ratio).

Results: The vesicles revealed vesicle size (VS) ranging from 133.1 to 851.3?nm, zeta potential (ZP) ?43.8 to ?82.8?mV, entrapment efficiency (EE%) from 66.7 to 88.7%, and Zt release after 4?h up to 67%. Optimized niosomal formulation (F11) depicted the smallest VS (133.1?nm), highest EE (88.7%), high ZP (?80.6?mV) and satisfactory release after 4?h (61.5%). There was a significant difference (p <.05) in drug permeation after 8?h for niosomal F11(460.98?ug/cm²) and niosomal F11 loaded Emulgel (336.92?ug/cm²) compared to plain Zt loaded emulgel (160.83?ug/cm²). Niosomal F11 loaded emulgel showed thixotropic behavior of rapid recovery, significant bioavailability and pharmacokinetic parameters as compared to the plain Zt-loaded Emulgel.

Conclusion: Optimized F11 represents a promising formulation for transdermal drug delivery system to treat both topical and systemic diseases.     

Critical evaluation of permeation enhancers for oral mucosal drug delivery

Background: Drug delivery via oral mucosa is an alternative method of systemic administration for various classes of therapeutic agents. Among the oral mucosae, buccal and sublingual mucosae are the primary focus for drug delivery. Buccal delivery offers a clear advantage over the peroral route by avoidance of intestinal and hepatic first-pass metabolism. However, despite offering the possibility of improved systemic drug delivery, buccal administration has been utilized for relatively few pharmaceutical products so far. One of the major limitations associated with buccal delivery is low permeation of therapeutic agents across the mucosa. Various substances have been explored as permeation enhancers to increase the flux/absorption of drugs through the mucosa, but irritation, membrane damage, and toxicity are always associated with them and limit their use. A clinically accepted permeation enhancer must increase membrane permeability without causing toxicity and permanent membrane damage. To date, the information available on oral mucosal permeation enhancement is much less than transdermal enhancement, though oral mucosa is more resistant to damage than other mucosal membranes. This article reviews the various categories of permeation enhancers for oral mucosal drug delivery, their mechanism of action, their usefulness, and the limitations associated with their use. Conclusion: To optimize the concentration of enhancer to limit its toxicity while facilitating an enhancing effect reproducibly will be a big challenge for future developments. Advances in permeability modulation and formulation with appropriate enhancers can provide for effective and feasible buccal drug delivery for many drugs, which otherwise have to be injected or ingested with water.     

Ocular Permeability of Pirenzepine Hydrochloride Enhanced by Methoxy poly(ethylene glycol)–poly(D,L-lactide) Block Copolymer

Methoxy poly(ethylene glycol)–poly(D,L-lactide) block copolymer was tested as an ocular permeation enhancer for pirenzepine hydrochloride. The block copolymers with the methoxy poly(ethylene glycol) to poly(D,L-lactide) weight ratio of 80/20, 50/50, 40/60 were synthesized by a ring-opening polymerization procedure. In vitro transcorneal experiments demonstrated that the block copolymer 80/20 significantly enhanced the transcorneal permeation of pirenzepine at the mass ratio of 1/1.4 (pirenzepine hydrochloride/copolymer). Interaction between pirenzepine and copolymer was identified by infrared spectroscopy analysis and dialysis experiments. Ocular pharmacokinetics of pirenzepine/copolymer preparation by in vivo instillation experiments confirmed that block copolymer could enhance the ocular penetration of pirenzepine. Ocular chronic toxicity experiments of block copolymer and pirenzepine/copolymer preparation were studied on rabbits, and no significant toxicity in both groups was observed within 9 months. It could conclude that pirenzepine/copolymer preparation is effective and safe in ocular delivery of pirenzepine.     

Pharmacodynamics of a losartan transdermal system for the treatment of hypertension

Aims: Transdermal therapeutic systems were developed using the polymers, Eudragit E 100 and polyvinyl pyrrolidone VA 64 in a film casting assembly. The medicated films were evaluated for physical properties, in vitro drug release studies, in vitro skin permeation studies, and pharmacodynamic studies. Results: The physical parameters were found to be very satisfactory with high drug content (>99%). The in vitro drug release studies were performed using paddle-over-disc assembly specified in USP XXIII. The pharmacodynamic studies were carried out using tail cuff method in Wistar albino rats. Hypertension was induced by methyl prednisolone acetate subcutaneously for 2 weeks. The developed matrix patch was found to decrease the blood pressure (25.42% reduction in mean systolic blood pressure of rats) significantly (P < 0.001) in proximity of the normal value and it was maintained for 24 hours. Conclusion: It can be concluded that the developed transdermal matrix patch holds promise for the management of hypertension that needs to be validated by clinical trials.     

Synthesis and in vitro characterization of a novel PAA–ATP conjugate

The objective of this study was to improve the multifunctional properties of poly(acrylic acid) (PAA) by covalent attachment of 4-aminothiophenol (ATP) to its backbone. The permeation enhancing effect of PAA–ATP together with glutathione was evaluated in Ussing-type chambers using fluorescein isothiocyanate dextran as model compound. The mucoadhesive properties were evaluated in vitro on freshly excised porcine intestinal mucosa through the rotating cylinder method. The resulting conjugates PAA–ATP1 and PAA–ATP2 displayed 168 ± 35 and 426 ± 55 μmol immobilized free thiol groups per gram polymer, respectively. In addition, 279 ± 28 and 139 ± 22 μmol disulfide bonds per gram polymer, respectively, were identified on PAA–ATP1 and PAA–ATP2. Within disintegration studies in aqueous buffer solution, the modified polymers showed improved cohesive properties. Because of the immobilization of ATP, the swelling of PAA–ATP1 and PAA–ATP2 improved 12.0- and 17.8-fold, respectively. The adhesion times of the conjugates PAA–ATP1 and PAA–ATP2 were more than 20- and 30-fold increased in comparison to unmodified PAA. Furthermore, conjugates PAA–ATP1 and PAA–ATP2 exhibited a 1.86- and 2.07-fold higher permeation enhancing effect, respectively, over unmodified PAA. According to these results, PAA–ATP conjugates represent a very promising novel type of thiomer for the development of various mucoadhesive drug delivery systems.     

Absorption and desorption of H by NbMo alloys at high temperature

Absorption and desorption of hydrogen have been investigated in Nb₉₅Mo₅ and Nb₈₀Mo₂₀ alloys over wide temperature ranges. On continuous heating H desorption from Nb₉₅Mo₅ was found to take place between 800 and 1000 K and from Nb₈₀Mo₂₀ between 900 and 1100 K. The observed increase in the desorption temperature with increasing Mo content has been attributed to a higher stability of the Mo and NbMo oxides with respect to those of Nb. The solid–gas reaction during absorption was first order and the rate limiting process consisted in the penetration of H atoms through surface oxides. At high temperatures and in the presence of H the oxides are expected to become permeable to H due to the reduction of higher valence to lower valence oxides. The values of the activation energy for H diffusion within the oxide films were 0.82 ± 0.04 eV for Nb₉₅Mo₅ and 1.1 ± 0.1 eV for Nb₈₀Mo₂₀. The thicknesses of the oxide films estimated from the absorption data were of the order of 1 μm.     

Ti-600合金的热稳定性

研究了Ti-600合金镦制饼材600 ℃热暴露前后室温拉伸性能的变化,并观察合金的拉伸断口、分析其断裂机制。结果表明,600 ℃热暴露100 h后,毛坯热暴露试样的强度较热暴露前固溶时效试样(STA)的提高了3%左右,延伸率降低20%左右;热暴露试样的强度稍有降低,延伸率则降低了45%左右。STA试样室温拉伸断裂起源于试样中心位置,断口形貌呈现韧窝型断裂特征;毛坯热暴露试样断口上可见解理小平面与韧窝并存的特征,为混合型断口;试样热暴露以后,裂纹萌生于试样表面,断口上观察到解理小平面,合金的断裂沿片层α相界面扩展。热暴露试样表层有脆性富氧层存在,富氧层内易诱发细微裂纹并向基体扩展。表面渗氧是Ti-600合金热暴露后塑性下降的重要原因之一     

煤炭地下气化炉型及工艺

为探讨不同煤层条件下地下气化炉结构及气化工艺,在模型试验和现场试验的基础上研究了煤炭地下气化有井式和无井式气化炉结构及其工艺参数,形成了有井式“长通道、大断面、两阶段”气化工艺和无井式渗透式气化方法.试验结果表明:空气气化时可获得热值在4.18 MJ/Nm3以上的煤气;富氧气化时,当富氧体积分数由30％上升到80％时,煤气中有效组分(H2+CO+CH4)体积分数由30％上升到60％;两阶段气化第2阶段可生产H2组分体积分数在40％、热值在11.45 MJ/Nm3以上的煤气.无井式渗透式气化通道贯通参数为:当供风压力0.75 MPa、供风流量600 Nm3/h时,贯通速度为0.34 m/d,通道当量直径0.39m,正向供风气化和反向供风气化能获得相同质量的煤气.     

Effect of Argon Ion Sputtering of Surface on Hydrogen Permeation through Vanadium

In order to measure the hydrogen permeation rate through V with atomically cleaned surface, an Ar ion sputtering apparatus has been installed in the hydrogen permeability measuring system. The permeation rate of the initial specimen was found to be increased by about one order of magnitude after Ar ion sputtering of its upstream side surface. Repeating of such a sputter-cleaning was not so much effective in increasing the steady state permeation rate as the initial sputtering was, but it accelerated the transient response rate by a factor of 2 or 3. The transient response rate was also accelerated by the increase of hydrogen pressure, but this effect tended to be diminished by the sputter-cleaning of specimen surface. The surface impurity layer on the downstream side of specimen was also inferred to act as a diffusion barrier affecting the steady state permeation rate. The present value of activation energy for hydrogen permeation through V at temperatures below 873 K was the smallest one ever obtained, showing that the surface effect was minimized in the present study on account of the surface sputter-cleaning in addition to the ultra high vacuum system.     

Enrichment and Volume Reduction of Tritiated Water Using Electrolysis Cell Having Hydrogen Permeable Cathode

The electrolysis rate and the separation factor for hydrogen isotopes are measured using the electrolysis cell having the hydrogen permeable cathode. As the hydrogen gas without the vapor of electrolyte is obtained by this method, decrease of the apparent separation factor by mixing with vapor can be avoided. It is also observed in this study that enrichment and volume reduction of tritiated water using the bipolar electrode electrolysis cell is effective because it gives small loss of tritium from the cell during volume reduction. The separation factor obtained in this study indicates that attachment of two or three sub-cells is enough for volume reduction of tritiated water.