以油包水型微乳为载体促进氟尿嘧啶的经皮渗透

以磺化琥珀酸二辛酯钠 (AOT) 为主要表面活性剂,制备氟尿嘧啶油包水型微乳制剂,以促进药物的经皮渗透。以伪三元相图为基础,依据微乳区域大小, 初步筛选微乳处方;用改进的Franz扩散池和离体小鼠皮肤研究氟尿嘧啶的透皮速率,以单位面积的透皮累积渗透量 (Q_n) 为指标, 考察微乳处方中助表面活性剂的种类、水相比例、混合表面活性剂比例、表面活性剂和助表面活性剂质量比和载药量对离体鼠皮透皮吸收的影响, 优化处方。结果表明,氟尿嘧啶微乳的优化处方为含药0.5%（w/v）,水30%,混合表面活性剂（AOT/Tween 85, K_m = 2）20%, 油相（IPM）49.5%,经皮渗透符合一级速率方程,12 h累积渗透量为（1 355.5 ± 41.1）μg·cm^-2, 分别为0.5%药物水溶液和2.5%（w/w）市售乳膏（O/W）的19.1和7倍。水/AOT/Tween 85/IPM微乳系统能促进5-氟尿嘧啶的透皮吸收, 可以作为氟尿嘧啶等亲水性但水溶性差和渗透性差的药物的新型经皮给药载体。

     

含电解质的W/O型微乳作为氟尿嘧啶透皮给药载体的研究

通过电解质氯化钠(NaCl)的加入,制备含水量高、载药量高且透过能力强的氟尿嘧啶(5-Fu)W/O型微乳,并研究其体外透皮特性及皮肤刺激性。以肉豆蔻酸异丙酯(IPM)为油相,磺化琥珀酸二辛酯钠(AOT)为表面活性剂,Tween 85为助表面活性剂,在室温下采用磁力搅拌法滴加NaCl溶液至油相中,形成空白微乳后直接加入5-Fu粉末,即形成5-Fu微乳。以伪三元相图为基础、单位面积的透皮累积透过量(Qn)为指标,用改进的Franz扩散池和离体小鼠皮肤考察微乳处方中含水量和载药量对离体鼠皮透过量的影响,优化处方。以表面张力、黏度和电导率为指标,研究NaCl/AOT-Tween 85/IPM微乳的理化性质,并对最优处方的皮肤刺激性进行初步评价。结果表明,5-Fu微乳的优化处方为含药0.7%(w/v),0.05 mol·L-1 NaCl溶液50%,混合表面活性剂(AOT/Tween 85,Km=2)20%,油相29.3%。12 h累积透过量为(2 013.4±41.6)μg.cm-2,分别为0.7%药物水溶液和2.5%(w/w)市售乳膏(O/W)的20.23倍和10.38倍。该微乳具有一定的刺激性,但停药后可迅速恢复。...     

Microemulsion-based hydrogel formulation of ibuprofen for topical delivery

The purpose of this study was to construct microemulsion-base hydrogel formulation for topical delivery of ibuprofen. Ethyl oleate (EO) was screened as the oil phase of microemulsions, due to a good solubilizing capacity of the microemulison systems and excellent skin permeation rate of ibuprofen. The pseudo-ternary phase diagrams for microemulsion regions were constructed using ethyl oleate as the oil, Tween 80 as the surfactant, propylene glycol as the cosurfactant. Various microemulsion formulations were prepared and the abilities of various microemulsions to deliver ibuprofen through the skin were evaluated in vitro using Franz diffusion cells fitted with porcine skins. The in vitro permeation data showed that microemulsions increased the permeation rate of ibuprofen 5.72-30.0 times over the saturated solution. The optimum formulation consisted of 3% ibuprofen, 6% EO, 30% Tween 80/PG (2:1) and water, showed a high permeation rate of 38.06 microg cm(-2) h(-1). Xanthan gum as a gel matrix was used to construct the microemulsion-based hydrogel for improving the viscosity of microemulsion for topical administration. The studied microemulsion-based hydrogel showed a good stability. These results indicate that the studied microemulsion-based hydrogel may be a promising vehicle for topical delivery of ibuprofen.     

Formulation,optimization and evaluation of transferosomal gel for transdermal insulin delivery

The present study deals with the development of transferosomal gel containing insulin by reverse phase evaporation method for painless insulin delivery for use in the treatment of insulin dependent diabetes mellitus. The effect of independent process variables like ratio of lipids (soya lecithin:cholesterol), ratio of lipids and surfactants, and ratio of surfactants (Tween 80:sodium deoxycholate) on the in vitro permeation flux (μg/cm²/h) of formulated transferosomal gels containing insulin through porcine ear skin was optimized using 2³ factorial design. The optimal permeation flux was achieved as 13.50 ± 0.22 μg/cm²/h with drug entrapment efficiency of 56.55 ± 0.37% and average vesicle diameter range, 625–815 nm. The in vitro insulin permeation through porcine ear skin from these transferosomal gel followed zero-order kinetics (R² = 0.9232–0.9989) over a period of 24 h with case-II transport mechanism. The in vitro skin permeation of insulin from optimized transferosomal gel by iontophoretic influence (with 0.5 mA/cm² current supply) also provided further enhancement of permeation flux to 17.60 ± 0.03 μg/cm²/h. The in vivo study of optimized transferosomal gel in alloxan-induced diabetic rat has demonstrated prolonged hypoglycemic effect in diabetic rats over 24 h after transdermal administration.     

酮基布洛芬贴片的制备及体外渗透性研究

目的：观察环丙沙星治疗下呼吸道感染的疗效。方法：１００例患者（男性５２例,女性４８例,年龄（４５±８）ａ用药剂量为５００ｍｇ,每１２ｈ口服１次,疗程一般为７～２１ｄ。结果：临床总有效率为９２０％,细菌清除率为８７２％,对革兰氏阳性及阴性菌均有效,敏感菌百分率达８８５％,特别对铜绿假单胞菌感染也有较好的疗效。结论：环丙沙星治疗下呼吸道感染疗效满意,副作用少,是安全、方便、可靠的有效药物。     

氟康唑脂质体凝胶的制备及体外透皮实验（英文）

目的制备氟康唑脂质体凝胶,并研究其性质。方法以薄膜分散法制备氟康唑脂质体,透射电镜观察脂质体的形态,粒度分布仪测定粒径,透皮吸收扩散池测定脂质体凝胶的透皮吸收。结果氟康唑脂质体的包封率为47.68%。脂质体粒径均匀,平均粒径为250±8nm。氟康唑脂质体凝胶的累积透过量（25.27%）低于非脂质体凝胶（36.72%）,而脂质体凝胶的药物皮内滞留量（162±15μg·cm^-2于非脂质体凝胶（48±6μg·cm^-2结论氟康唑脂质体凝胶剂可显著提高药物的皮内滞留量,有望成为氟康唑的一种外用新剂型。     

Microemulsion-based drug delivery system for transnasal delivery of Carbamazepine: preliminary brain-targeting study

This study reports the development and evaluation of Carbamazepine (CMP)-loaded microemulsions (CMPME) for intranasal delivery in the treatment of epilepsy. The CMPME was prepared by the spontaneous emulsification method and characterized for physicochemical parameters. All formulations were radiolabeled with ^99mTc (technetium) and biodistribution of CMP in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rats was also performed to determine the uptake of the CMP into the brain. CMPME were found crystal clear and stable with average globule size of 34.11?±?1.41?nm. ^99mTc-labeled CMP solution (CMPS)/CMPME/CMP mucoadhesive microemulsion (CMPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8?h following intranasal administration of CMPMME compared to intravenous CMPME was found to be 2- to 3-fold higher signifying larger extent of distribution of the CMP in brain. Drug targeting efficiency and direct drug transport were found to be highest for CMPMME post-intranasal administration compared to intravenous CMP. Rat brain scintigraphy also demonstrated higher intranasal uptake of the CMP into the brain. This investigation demonstrates a prompt and larger extent of transport of CMP into the brain through intranasal CMPMME, which may prove beneficial for treatment of epilepsy.     

Microemulsion-based media as novel drug delivery systems

Microemulsions are clear, stable, isotropic mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating a wide range of drug molecules. In order to appreciate the potential of microemulsions as delivery vehicles, this review gives an overview of the formation and phase behaviour and characterization of microemulsions. The use of microemulsions and closely related microemulsion-based systems as drug delivery vehicles is reviewed, with particular emphasis being placed on recent developments and future directions.     

In vitro evaluation of a hydroxypropyl cellulose gel system for transdermal delivery of timolol

In this work, the development of a gel reservoir for a timolol (TM) transdermal iontophoretic delivery system is investigated. TM gel is prepared using hydroxypropyl cellulose (HPC) and the permeability of TM from the gel through an artificial membrane (Polyflux) and pig stratum corneum (SC) is studied. For a constant TM donor concentration, the TM transport across the Polyflux membrane alone decreases when the concentration of the gel increases due to increase of the gel viscosity. For constant gel concentration, however, the TM permeation across the membrane increases when the TM donor concentration increases. In addition, no effect of the electrical current (iontophoresis, current density 0.5 mA cm-2) on the TM permeation is found. For the combination of the Polyflux membrane with pig SC, the TM transport is much lower than for the membrane alone and the SC fully controls the TM delivery. In this case, the application of electrical current enhances the TM delivery 13-15 times in comparison to passive (no current) transport. According to our estimation, the daily TM dose (10-60 mg) can be delivered by an iontophoretic patch with Polyflux membrane area of 6-36 cm2 containing 20% (w/w) HPC gel and 15 mg cm-3 of TM.     

Pharmaceutical development and clinical effectiveness of a novel gel technology for transdermal drug delivery

Transdermal gels are designed to deliver sustained drug amounts, resulting in systemically consistent levels. They represent an improvement compared with transdermal delivery by patches because they offer more dosage flexibility, less irritation potential and a better cosmetic appearance. Advanced Transdermal Delivery (ATD) gel technology was developed in order to provide enhanced passive skin permeation of various active drugs for the treatment of many conditions, including hypogonadism, female sexual dysfunction, postmenopausal symptoms, overactive bladder and anxiety. The technology consists of a combination of solvent systems and permeation enhancers enabling systemic drug delivery, and is covered by many patents. Pharmaceutical development of formulations based on the technology allowed optimisation of physicochemical parameters (rheological profile, pH) as well as skin permeation properties (type and concentration of permeation enhancers, thermodynamic activity of the drug). This gel technology has demonstrated to be efficient for many drugs, as shown in the preclinical and clinical pharmacokinetic studies presented in this technology evaluation.     

Pharmaceutical development and clinical effectiveness of a novel gel technology for transdermal drug delivery

Transdermal gels are designed to deliver sustained drug amounts, resulting in systemically consistent levels. They represent an improvement compared with transdermal delivery by patches because they offer more dosage flexibility, less irritation potential and a better cosmetic appearance. Advanced Transdermal Delivery? (ATD?) gel technology was developed in order to provide enhanced passive skin permeation of various active drugs for the treatment of many conditions, including hypogonadism, female sexual dysfunction, postmenopausal symptoms, overactive bladder and anxiety. The technology consists of a combination of solvent systems and permeation enhancers enabling systemic drug delivery, and is covered by many patents. Pharmaceutical development of formulations based on the technology allowed optimisation of physicochemical parameters (rheological profile, pH) as well as skin permeation properties (type and concentration of permeation enhancers, thermodynamic activity of the drug). This gel technology has demonstrated to be efficient for many drugs, as shown in the preclinical and clinical pharmacokinetic studies presented in this technology evaluation.     

Microemulsion-based media as novel drug delivery systems

Microemulsions are clear, stable, isotropic mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating a wide range of drug molecules. In order to appreciate the potential of microemulsions as delivery vehicles, this review gives an overview of the formation and phase behaviour and characterization of microemulsions. The use of microemulsions and closely related microemulsion-based systems as drug delivery vehicles is reviewed, with particular emphasis being placed on recent developments and future directions.     

Bioadhesive film formed from a novel organic-inorganic hybrid gel for transdermal drug delivery system

A novel organic-inorganic hybrid film-forming agent for TDDS was developed by a modified poly(vinyl alcohol) (PVA) gel using γ-(glycidyloxypropyl)trimethoxysilane (GPTMS) as an inorganic-modifying agent, poly(N-vinyl pyrrolidone) (PVP) as a tackifier and glycerol (GLY) as a plasticizer. The prepared gels can be applied to the skin by a coating method and in situ form very thin and transparent films with good performance, comfortable feel and cosmetic attractiveness. The key properties of the bioadhesive films produced from the hybrid gels were investigated and the results showed that the incorporation of appropriate GPTMS (GPTMS/(PVA + GPTMS) in the range of 20-30%) into the PVA matrix not only can significantly enhance mechanical strength and skin adhesion properties of the resultant film, but also can decrease the crystalline regions of PVA and hence facilitate the diffusion of water vapor and drug. Furthermore, the investigations into in vivo skin irritation suggested the films caused non-irritation to skin after topical application for 120 h. In conclusion, the bioadhesive films formed from organic-inorganic hybrid gels possessed very good qualities for application on the skin and may provide a promising formulation for TDDS, especially when the patient acceptability from an aesthetic perspective of the dosage form is a prime consideration.     

Transfersomes for transdermal drug delivery

Transfersomes (Idea AG) are a form of elastic or deformable vesicle, which were first introduced in the early 1990s. Elasticity is generated by incorporation of an edge activator in the lipid bilayer structure. The original composition of these vesicles was soya phosphatidyl choline incorporating sodium cholate and a small concentration of ethanol. Transfersomes are applied in a non-occluded method to the skin and have been shown to permeate through the stratum corneum lipid lamellar regions as a result of the hydration or osmotic force in the skin. They have been used as drug carriers for a range of small molecules, peptides, proteins and vaccines, both in vitro and in vivo. It has been claimed by Idea AG that intact Transfersomes penetrate through the stratum corneum and the underlying viable skin into the blood circulation. However, this has not been substantiated by other research groups who have extensively probed the mechanism of penetration and interaction of elastic vesicles in the skin. Structural changes in the stratum corneum have been identified, and intact elastic vesicles visualised within the stratum corneum lipid lamellar regions, but no intact vesicles have been ascertained in the viable tissues. Using the principle of incorporating an edge-activator agent into a bilayer structure, a number of other elastic vesicle compositions have been evaluated. This review describes the research into the development and evaluation of Transfersomes and elastic vesicles as topical and transdermal delivery systems.     

Microneedles for transdermal drug delivery

The success of transdermal drug delivery has been severely limited by the inability of most drugs to enter the skin at therapeutically useful rates. Recently, the use of micron-scale needles in increasing skin permeability has been proposed and shown to dramatically increase transdermal delivery, especially for macromolecules. Using the tools of the microelectronics industry, microneedles have been fabricated with a range of sizes, shapes and materials. Most drug delivery studies have emphasized solid microneedles, which have been shown to increase skin permeability to a broad range of molecules and nanoparticles in vitro. In vivo studies have demonstrated delivery of oligonucleotides, reduction of blood glucose level by insulin, and induction of immune responses from protein and DNA vaccines. For these studies, needle arrays have been used to pierce holes into skin to increase transport by diffusion or iontophoresis or as drug carriers that release drug into the skin from a microneedle surface coating. Hollow microneedles have also been developed and shown to microinject insulin to diabetic rats. To address practical applications of microneedles, the ratio of microneedle fracture force to skin insertion force (i.e. margin of safety) was found to be optimal for needles with small tip radius and large wall thickness. Microneedles inserted into the skin of human subjects were reported as painless. Together, these results suggest that microneedles represent a promising technology to deliver therapeutic compounds into the skin for a range of possible applications.     

Nanoparticle delivery for transdermal HRT

Nanomedicine is an emerging technology and the first nano-engineered medical products have come to light in the last decade. Transdermal drug delivery has significant advantages compared to other routes of drug administration. Nanoparticles unique physical and chemical properties enable transport of substances directly into the skin. The objective of this paper is to review different aspects of nanoparticle delivery, generally, and discuss its current use for transdermal hormone therapy. Transdermal estrogen therapy remains the most effective treatment for bothersome menopausal symptoms, particularly in those women for whom the potential adverse effects associated with “first pass” hepatic metabolism are to be avoided. Available alternatives for transdermal estrogen delivery include patches, gels, sprays and lotions. Other non-oral therapies which likewise avoid “first pass” hepatic metabolism include: subcutaneous implants and vaginal rings. Some of the transdermal products are associated with mild adverse skin effects such as redness and irritation, but more severe and bothersome consequences include blistering and tattooing. Even the mild adverse skin effects are frequently cited as reasons for discontinuation. Micellar nanoparticle estradiol emulsion (MNPEE) is a lotion-like therapy which constitutes an alternative transdermal delivery system not requiring the permeation enhancers or temporary skin digestion, both of which increase the possibility of irritation. MNPEE's advantages include low fluctuation of plasma estradiol concentrations, infrequent skin related adverse effects, and pleasant cosmetic-like moisturizing properties. The efficacy of MNPEE for management of menopausal vasomotor symptoms has been demonstrated in a randomized placebo controlled trial,¹ and the product is FDA approved for management of moderate to severe vasomotor symptoms. None of the observed adverse effects in the MNPEE group were statistically different from the placebo group.¹ Studies addressing inadvertent transference of estradiol to the male partners of menopausal women using this delivery technology have demonstrated small, but real amounts of transference, which do not exceed the normal physiological male estradiol range. MNPEE is safe and effective for treatment of vasomotor symptoms and represents the commercial validation of nanoparticle technology for transdermal delivery of estrogen therapy (ET) for postmenopausal women with vasomotor symptoms.     

Transfersomes for transdermal drug delivery

Transfersomes^® (Idea AG) are a form of elastic or deformable vesicle, which were first introduced in the early 1990s. Elasticity is generated by incorporation of an edge activator in the lipid bilayer structure. The original composition of these vesicles was soya phosphatidyl choline incorporating sodium cholate and a small concentration of ethanol. Transfersomes are applied in a non-occluded method to the skin and have been shown to permeate through the stratum corneum lipid lamellar regions as a result of the hydration or osmotic force in the skin. They have been used as drug carriers for a range of small molecules, peptides, proteins and vaccines, both in vitro and in vivo. It has been claimed by Idea AG that intact Transfersomes penetrate through the stratum corneum and the underlying viable skin into the blood circulation. However, this has not been substantiated by other research groups who have extensively probed the mechanism of penetration and interaction of elastic vesicles in the skin. Structural changes in the stratum corneum have been identified, and intact elastic vesicles visualised within the stratum corneum lipid lamellar regions, but no intact vesicles have been ascertained in the viable tissues. Using the principle of incorporating an edge-activator agent into a bilayer structure, a number of other elastic vesicle compositions have been evaluated. This review describes the research into the development and evaluation of Transfersomes and elastic vesicles as topical and transdermal delivery systems.     

HPLC测定氟尿嘧啶凝胶剂的含量

目的建立高效液相色谱法测定氟尿嘧啶凝胶剂中氟尿嘧啶的含量.方法采用C18色谱柱,流动相为0.02 mol/L的NaH2PO4-H3PO4-Triethylamine(三乙胺)缓冲液(pH 3.03),流速1.0 ml/min,进样量50 μl,检测波长269 nm,室温条件.结果氟尿嘧啶浓度在0.5～500 μg/ml范围内呈良好线性关系(r=0.999 9),平均回收率为99.9%,RSD为0.52%.结论该方法快速,准确,重复性好,适用于氟尿嘧啶凝胶剂的质量控制.