透皮促进剂对肤康祛斑凝胶体外透皮吸收的影响

目的考察透皮促渗剂对肤康祛斑凝胶的主药熊果苷体外经皮渗透的影响。方法对优化后的肤康祛斑凝胶处方,以大鼠离体皮肤作为渗透屏障,用高效液相色谱法测定凝胶中熊果苷经皮透入接收液含量。考察氮酮、氮酮-薄荷油、氮酮-冰片作为促渗剂对熊果苷透皮吸收的影响。结果肤康祛斑凝胶中熊果苷的体外累积渗透率符合Weibull分布,以氮酮-薄荷油作为促渗剂的处方中,熊果苷累积渗透率最高,渗透促进剂的促透效果为:氮酮-薄荷油>氮酮-冰片>氮酮。结论以氮酮-薄荷油作为促渗剂,对熊果苷有较好的促渗作用。     

渗透促进剂对盐酸普萘洛尔经皮渗透的影响

目的:研究常用渗透促进剂对盐酸普萘洛尔经皮渗透的影响。方法:采用改良Franz扩散池,以0.9%氯化钠溶液作为接收液,以增渗倍数(ER)为考察指标,考察1%、3%、5%水溶性氮酮溶液,1%、3%、5%油溶性氮酮溶液,1%水溶性氮酮丙二醇溶液,5%、10%油酸溶液,丙二醇等10种渗透促进剂对盐酸普萘洛尔透过离体大鼠腹部皮肤的影响。结果:渗透促进效果分别为3%油溶性氮酮溶液>10%油酸溶液>1%水溶性氮酮丙二醇溶液>5%油溶性氮酮溶液>1%水溶性氮酮溶液>3%水溶性氮酮溶液>1%油溶性氮酮溶液>5%水溶性氮酮溶液>5%油酸溶液>丙二醇。结论:油溶性渗透促进剂对盐酸普萘洛尔的经皮渗透促进作用有强于水溶性渗透促进剂的趋势。     

盐酸丁螺环酮透皮促渗剂选择及其透皮机制的研究

目的研究透皮促渗剂对盐酸丁螺环酮体外经皮渗透的影响以及盐酸丁螺环酮的透皮机制。方法采用改良Franz扩散池,比较不同促渗剂种类、浓度、配比对盐酸丁螺环酮的促渗效果,同时通过改变扩散池的介质pH及皮肤的状态,研究药物的透皮机制。结果采用3%氮酮为透皮促渗剂时药物透过量最大。盐酸丁螺环酮随着分子型浓度的升高透过量也随之增加,皮肤去除角质层后,药物的透过量显著大于完整皮肤,而完整皮肤的贮库效应大于去角质皮肤。结论药物透皮以3%氮酮为透皮促进剂促渗效果最佳。盐酸丁螺环酮主要是以分子型透过皮肤,药物的透皮屏障与贮库效应发生的主要部位是皮肤的角质层。     

促透皮吸收剂对菌克软膏中硝酸咪康唑透皮吸收的影响

目的考察促透皮吸收剂对菌克软膏中硝酸咪康唑透皮吸收的影响,并筛选最佳透皮吸收剂及用量。方法采用Franz扩散池法,以离体裸鼠皮为透皮屏障,HPLC法测定含量,计算累积透皮量。结果累积透皮量检测表明,不同促渗剂的促渗强弱顺序依次为3%氮酮>5%丙二醇>5%油酸>3%薄荷脑>不加促透剂,不同用量的氮酮促渗作用强弱顺序依次为5%氮酮>3%氮酮>1%氮酮>菌克。结论几种促透剂对菌克软膏中硝酸咪康唑均有促透皮吸收作用,其中氮酮的促透效果最好,且5%氮酮的促透效果最为明显。     

抗敏止痒乳膏透皮效果的实验研究

目的考察抗敏止痒乳膏中盐酸利多卡因和马来酸氯苯那敏的局部透皮效果.方法应用简单小室法,以离体大鼠皮肤为透皮屏障,用紫外分光光度法测定体外接受液中盐酸利多卡因和马来酸氯苯那敏的含量,进而计算累积透皮量和透皮率,并与加入氮酮的抗敏止痒乳膏的透皮效果进行了实验性比较.结果盐酸利多卡因和马来酸氯苯那敏的8小时累积透皮量与透皮率分别为(122.3±3.21)μg/ml与(91.95±2.41)%和(27.84±2.21)μg/ml与(83.53±6.63)%,与加入氮酮的制剂透皮效果比较无差异(P＞0.05).结论抗敏止痒乳膏的局部透皮效果良好.     

4种透皮吸收促进剂对盐酸苯海拉明透皮性能的影响

目的:研究油酸、1,3-丙二醇、月桂氮酮、丙三醇4种透皮吸收促进剂对盐酸苯海拉明透皮性能的影响。方法:在一定量的盐酸苯海拉明溶液中分别加入4种不同浓度的透皮吸收促进剂,采用改良Franz扩散池进行体外透皮吸收试验,测定不同浓度下不同透皮吸收促进剂的24h累积透过量(Q)。结果:以Q为指标,促透作用油酸>1,3-丙二醇>月桂氮酮>丙三醇,且前三者分别以0.5%、0.5%、0.2%为最佳促透浓度,丙三醇未见有明显的促透作用。结论:4种透皮吸收促进剂在一定浓度下均可增强盐酸苯海拉明局部给药制剂的透皮吸收作用。     

咳喘穴位贴片透皮促进剂用量的筛选

目的:优选咳喘穴位贴片透皮促进剂——氮酮的最佳用量。方法:以丁香酚累积渗透百分率为评价指标,用离体兔皮及Franz扩散池进行体外透皮试验,考察氮酮用量分别为0%、1%、3%的透皮速率及透皮总量,建立透皮动力学模型,提取并比较透皮特性参数。结果:加0%、1%氮酮的药物透皮动力学模型为Higuchi模型;加3%氮酮的药物透皮动力学模型为威布尔模型。加1%氮酮透皮速度最快,是未加氮酮的5.019倍;累积透皮总量最多,是未加氮酮的2.489倍。结论:氮酮用量为1%时透皮速度最快,透皮量最大。     

普萘洛尔体外经皮渗透及氮酮的促渗作用

本文利用离体兔皮为渗透屏障研究了胶粘剂中分散型普萘洛尔贴膜剂的体外经皮渗透性，考察了透皮吸收促进剂氮酮的增渗效果和该贴膜剂的体外释放行为．结果表明：贴膜剂中普萘洛尔可经皮渗透（渗透速率常数２．２６μｇ／ｃｍ２·ｈ）；氮酮具有促进普萘洛尔经皮渗透作用（渗透速率常数３．０９μｇ／ｃｍ２·ｈ）．普萘洛尔经皮渗透过程遵循零级动力学方程；且体外释药行为可用ｃｈａｎｄｒａｓｅｋａｒａｎ溶出扩散控制转运机制加以解释；该贴膜为皮控型经皮治疗系统．     

氮酮对胰岛素体外经皮渗透性的影响

目的 研究氮酮对胰岛素体外经皮渗透性的影响.方法 用扩散池进行体外经皮渗透实验,以酶联免疫法测定胰岛素的渗透量.结果 加入不同浓度的氮酮,释药速度不同.胰岛素的释放速度为4%氮酮≈2%氮酮>1%氮酮>0.5%氮酮>0%氮酮.结论 氮酮能促进胰岛素的体外透皮吸收,加入2%以上的氮酮促透效果最佳.     

不同促渗剂对盐酸芦氟沙星体外经皮渗透的影响

目的　研究几种常用促渗剂对盐酸芦氟沙星体外经皮渗透的影响。方法　用紫外分光光度法检测浓度 ,采用改进Franz扩散池 ,比较几种常用促渗剂对盐酸芦氟沙星渗透系数的影响。结果　1%氮酮和 1%氮酮 10 %丙二醇可显著增大盐酸芦氟沙星的渗透系数 (P <0 .0 1)。结论　 1%氮酮和1%氮酮 10 %丙二醇可作为促渗剂用于盐酸芦氟沙星的透皮吸收制剂     

促渗剂对布洛芬透皮吸收速率的影响

以简单小室法研究了布洛芬分别在不加助渗剂、加１％月桂氮　酮、加１％尿素、加１％月桂氮　酮及１％吐温－８０时渗过离体小白鼠皮肤的吸收效果。结果表明，月桂氮　酮有显著的吸收促进作用，尿素次之。吐温－８０则有抑制作用。     

The Effect of Tertiary Butyl Alcohol on the Resistance of the Dry Product Layer During Primary Drying

The addition of low concentrations of tertiary butyl alcohol (TBA) (3–10% w/v) was shown to influence the crystal habit of ice by causing the formation of needle-shaped ice crystals. The sublimation of these needle-shaped ice crystals resulted in a dry product layer with little resistance. Using a microbalance technique it was shown that the primary drying stage for 5% w/v sucrose solution was considerably shorter when 5% w/v TBA was added due to a lower resistance of the dried cake above the frozen solution. In the absence of TBA the frozen solution had an initially high resistance of approximately 60 cm² torr hr/gm due to the formation of a skin; once the skin cracked the resistance reached a constant value of 10 cm² torr hr/gm. The solution containing TBA had a dried product resistance in the range of 0.5–3 cm² torr hr/gm. The total time required to dry the product in the absence of TBA in the microbalance was 100 hours as compared to 10 hours for the solution containing 5% w/v TBA. The specific surface area of the freeze-dried cake produced from a 5% w/v sucrose solution containing 5% w/v TBA was 8.57 m²/gm as compared to 0.67 m²/gm for solutions not containing TBA. The addition of TBA to the sucrose solution did not change the collapse temperature, but the rapid rate of sublimation prevented the product from ever reaching the collapse temperature.     

Penetration-enhancing effect of ethanolic solution of menthol on transdermal permeation of ondansetron hydrochloride across rat epidermis

The aim of this investigation was to study the effect of an ethanol-water solvent system and ehtanolic solution of menthol on the permeation of ondansetron hydrochloride across the rat epidermis in order to select a suitable ethanol-water vehicle and optimal concentration of menthol for the development of a transdermal therapeutic system. The solubility of ondansetron hydrochloride in ethanol, water and selected concenetrtaion of ethanol-water vehicles (20:80 v/v, 40:60 v/v and 60:40 v/v) was determined. The effect of these solvent vehicles, containing 1.5% w/v of ondansetron hydrochloride, on the in vitro permeation of the drug was studied across the rat epidermis. The highest permeation was observed from 60% v/v of ethanol-water vehicle that showed highest solubilty. Hence, the hydroxypropyl cellulose (HPC) (2% w/w) gel formulations containing 1.5% w/w of ondansetron hydrochloride and selected concentrations of menthol (0, 2, 4, 8 and 10% w/w) were prepared using 60% v/v of ethanol-water vehicle, and subjected to in vitro permeation of the drug across rat epidermis. The transdermal permeation of ondansetron hydrochloride was enhanced markedly by the addition of menthol to HPC gel drug reservoir formulations. A maximum flux of ondansetron hydrochloride (77.85 ± 2.85 μ g/cm^2.h) was observed with a mean enhancement ratio of 13.06 when menthol was incorporated at a concentration of 8% w/w in HPC gels. However, there was no significant increase in the drug flux with 10% w/w menthol when compared to that obtained with 8% w/w of menthol in HPC gel formulations. The results suggest that 2% w/w HPC gel drug reservoir formulation, prepared with 60% v/v ethanol-water, containing 8% w/w of menthol provides an optimal transdermal permeation of ondansetron hydrochloride.     

Formulation of an HPMC gel drug reservoir system with ethanol-water as a solvent system and limonene as a penetration enhancer for enhancing in vitro transdermal delivery of nicorandil

The objective of the present study was to formulate a hydroxypropyl methylcellulose (HPMC) gel drug reservoir system with ethanol-water as a solvent system and limonene as a penetration enhancer for enhancing the transdermal delivery of nicorandil so as to develop and fabricate a membrane-moderated transdermal therapeutic system (TTS). The in vitro permeation of nicorandil was determined across rat abdominal skin from a solvent system consisting of ethanol or various proportions of ethanol and water. The ethanol-water (70:30 v/v) solvent system that provided an optimal transdermal permeation was used in formulating an HPMC gel drug reservoir system with selected concentrations (0% w/w, 4% w/w, 6% w/w, 8% w/w or 10% w/w) of limonene as a penetration enhancer for further enhancement of transdermal permeation of nicorandil. The amount of nicorandil permeated in 24 h was found increased with an increase in the concentration of limonene in the drug reservoir system up to a concentration of 6% w/w, but beyond this concentration there was no further increase in the amount of drug permeated. The flux of nicorandil was 370.9 +/- 4.2 microg/cm2 x h from the drug reservoir system with 6% w/w of limonene, which is about 2.6 times the required flux to be obtained across rat abdominal skin for producing the desired plasma concentration for the predetermined period in humans. The results of a Fourier Transform Infrared study indicated that limonene enhanced the percutaneous permeation of nicorandil by partially extracting the stratum corneum lipids. It is concluded that the HPMC gel drug reservoir system prepared with a 70:30 v/v ethanol-water solvent system containing 6% w/w of limonene is useful in designing and fabricating a membrane-moderated TTS of nicorandil.     

Penetration-Enhancing Effect of Ethanolic Solution of Menthol on Transdermal Permeation of Ondansetron Hydrochloride Across Rat Epidermis

The aim of this investigation was to study the effect of an ethanol-water solvent system and ehtanolic solution of menthol on the permeation of ondansetron hydrochloride across the rat epidermis in order to select a suitable ethanol-water vehicle and optimal concentration of menthol for the development of a transdermal therapeutic system. The solubility of ondansetron hydrochloride in ethanol, water and selected concenetrtaion of ethanol-water vehicles (20:80 v/v, 40:60 v/v and 60:40 v/v) was determined. The effect of these solvent vehicles, containing 1.5% w/v of ondansetron hydrochloride, on the in vitro permeation of the drug was studied across the rat epidermis. The highest permeation was observed from 60% v/v of ethanol-water vehicle that showed highest solubilty. Hence, the hydroxypropyl cellulose (HPC) (2% w/w) gel formulations containing 1.5% w/w of ondansetron hydrochloride and selected concentrations of menthol (0, 2, 4, 8 and 10% w/w) were prepared using 60% v/v of ethanol-water vehicle, and subjected to in vitro permeation of the drug across rat epidermis. The transdermal permeation of ondansetron hydrochloride was enhanced markedly by the addition of menthol to HPC gel drug reservoir formulations. A maximum flux of ondansetron hydrochloride (77.85 ± 2.85 μ g/cm^2.h) was observed with a mean enhancement ratio of 13.06 when menthol was incorporated at a concentration of 8% w/w in HPC gels. However, there was no significant increase in the drug flux with 10% w/w menthol when compared to that obtained with 8% w/w of menthol in HPC gel formulations. The results suggest that 2% w/w HPC gel drug reservoir formulation, prepared with 60% v/v ethanol-water, containing 8% w/w of menthol provides an optimal transdermal permeation of ondansetron hydrochloride.     

Penetration-enhancing effect of ethanol-water solvent system and ethanolic solution of carvone on transdermal permeability of nimodipine from HPMC gel across rat abdominal skin

The aim of this investigation was to find the effect of the ethanol-water solvent system and the ethanolic solution of carvone on the permeation of nimodipine across rat abdominal skin in order to select a suitable solvent system and optimal concentration of carvone for the development of membrane-moderated transdermal therapeutic system of nimodipine. The solubility of nimodipine in water, ethanol, and ethanol-water cosolvent systems, or the selected concentration of carvone [2% (w/w) to 12% (w/w)] in 60:40 (v/v) ethanol-water were determined. The effect of these solvents or cosolvent systems on the transdermal permeation of nimodipine was also studied using in vitro permeability studies across the rat abdominal skin. The co-solvent system containing 60:40 (v/v) of ethanol-water showed highest permeability across the rat abdominal skin. Further, the effect of ethanolic solution [60% (v/v) ethanol-water] of carvone [2% (w/w) to 12% (w/w)] on the in vitro permeation of nimodipine across the rat abdominal skin from 2% (w/w) hydroxypropyl methylcellulose (HPMC) gel was also investigated. The transdermal permeability of nimodipine across rat abdominal skin was enhanced further by the addition of carvone to HPMC gel prepared with 60% (v/v) of ethanol. There was a steady effect on the flux of nimodipine (161.02 +/- 4.14 microg/cm2/hr) with an enhancement ratio of 4.56 when carvone was incorporated at a concentration of 10% (w/w) in HPMC gels prepared with 60% (v/v) ethanol. The Fourier transform infrared data indicated that ethanolic solution of carvone increased the transdermal permeability of nimodipine across the rat abdominal skin by partial extraction of lipids in the stratum corneum. The results suggest that 10% (w/w) of carvone in 60% (v/v) ethanol-water, along with HPMC as antinucleating agent may be useful for enhancing the skin permeability of nimodipine from the membrane-moderated transdermal therapeutic system.     

Preparation and in vitro evaluation of mucoadhesive properties of alginate/chitosan microparticles containing prednisolone

This study describes the preparation of mucoadhesive alginate/chitosan microparticles containing prednisolone intended for colon-specific delivery. Two methods have been used for the preparation of the particles: the one-step method is the method in which prednisolone was dispersed within sodium alginate solution and this dispersion was then dropped in a solution containing both calcium chloride and chitosan. The two-step method consisted also of the dispersion of prednisolone in alginate solution and then dropping this dispersion into a solution containing calcium chloride, the particles were then transferred to a chitosan solution. The concentration of sodium alginate solution at 2% (w/v), various concentrations of calcium chloride solution (0.5-1.0%, w/v), chitosan solutions (0.5, 1.0 and 1.5%, w/v) and prednisolone drug load (2, 5, 10 and 15%, w/v) have been used. The results for both preparation methods show that the particle size and drug content were mainly depending on the amount of the drug concentration and not the amount of chitosan and calcium chloride. The in vitro mucoadhesive tests for particles prepared from both methods were carried out using the freshly excised gut of pigs. The particles prepared by the one-step method exhibited excellent mucoadhesive properties after 1h test. Increased chitosan concentrations from 0, 0.5, 1.0 to 1.5% (w/v) resulted in 43, 55, 82 and 88% of the particle remaining attached on the gut surface after 1 h, respectively. However, the particles prepared by the two-step method showed significant less mucoadhesion under the same experimental conditions. At chitosan concentrations of 0, 0.5, 1.0 and 1.5% (w/v) the amount of particles remaining attached to the mucosal surface of the pig gut after 1 h was 43, 3, 11 and 11%, respectively. The prednisolone release at a pH of 6.8 after 4 h was between 63 and 79% for the particles prepared by the one-step method and between 57 and 88% for the particles prepared by the two-step method with a prednisolone drug load of 5 and 10% (w/v), respectively. The results show that depending on the preparation method these chitosan coated alginate particles show different mucoadhesiveness whereas their other properties are not statistically significant different.     

Effect of penetration enhancers on the transdermal delivery of bupranolol through rat skin

Bupranolol (BPL) is a suitable drug candidate for transdermal drug delivery system development based on its favorable physicochemical and pharmacokinetic properties. The effect of different penetration enhancers on the permeation of BPL across rat skin was studied using side-by-side diffusion cells. 2-Pyrrolidone (PY), 1-methyl-2-pyrrolidone (MPY), and propylene glycol (PG) at various concentrations were used as penetration enhancers along with 0.4% w/v aqueous suspension of BPL. Menthol at different concentrations in isopropanol-water (6:4) mixture also was used as an enhancer wherein BPL at 0.4% w/v was completely solubilized. Skin pretreatment studies were carried out with all the above enhancers to understand their role in the penetration enhancement effect. PY and MPY at 5% w/v concentrations increased the permeation of BPL by 3.8- and 2.4-fold, respectively, versus control (p < .01). PG at 10% and 30 w/v concentrations increased the flux of BPL by 2.5- and 5.0-fold, respectively, versus control (p < .001). Menthol at 2% w/v concentration increased the flux of BPL by 3.8-fold (p < .01) and further increase in menthol concentration significantly decreased the flux of BPL. Overall, pyrrolidones and menthol at low concentrations (5% w/v or less) and PG at 30% w/v concentration were effective as penetration enhancers for BPL.     

Effect of carvone on the permeation of nimodipine from a membrane-moderated transdermal therapeutic system

The purpose of this investigation was to develop a membrane-moderated transdermal therapeutic system (TTS) of nimodipine using 2% w/w hydroxypropylmethylcellulose (HPMC) gel as a reservoir system containing 10% w/w of carvone (penetration enhancer) in 60% v/v ethanol. The flux of nimodipine through an ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer. The effect of a pressure-sensitive adhesive (TACKWHITE A 4MED) on the permeability of nimodipine through an EVA 2825 membrane (28% w/w vinyl acetate) or an EVA 2825 membrane/skin composite was also studied. An EVA 2825 membrane coated with TACKWHITE 4A MED was found to provide the required flux of nimodipine (117 +/- 5 microg/cm2/h) across rat abdominal skin. Thus a new transdermal therapeutic system for nimodipine was formulated using EVA 2825 membrane, coated with a pressure-sensitive adhesive TACKWHITE 4A MED, and 2% w/w HPMC gel as reservoir containing 10% w/w of carvone as a penetration enhancer. Studies in healthy human volunteers indicated that the TTS of nimodipine, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations.     

Penetration‐Enhancing Effect of Ethanol–Water Solvent System and Ethanolic Solution of Carvone on Transdermal Permeability of Nimodipine from HPMC Gel Across Rat Abdominal Skin

The aim of this investigation was to find the effect of the ethanol–water solvent system and the ethanolic solution of carvone on the permeation of nimodipine across rat abdominal skin in order to select a suitable solvent system and optimal concentration of carvone for the development of membrane‐moderated transdermal therapeutic system of nimodipine. The solubility of nimodipine in water, ethanol, and ethanol–water cosolvent systems, or the selected concentration of carvone [2% (w/w) to 12% (w/w)] in 60:40 (v/v) ethanol–water were determined. The effect of these solvents or cosolvent systems on the transdermal permeation of nimodipine was also studied using in vitro permeability studies across the rat abdominal skin. The cosolvent system containing 60:40 (v/v) of ethanol–water showed highest permeability across the rat abdominal skin. Further, the effect of ethanolic solution [60% (v/v) ethanol–water] of carvone [2% (w/w) to 12% (w/w)] on the in vitro permeation of nimodipine across the rat abdominal skin from 2% (w/w) hydroxypropyl methylcellulose (HPMC) gel was also investigated. The transdermal permeability of nimodipine across rat abdominal skin was enhanced further by the addition of carvone to HPMC gel prepared with 60% (v/v) of ethanol. There was a steady effect on the flux of nimodipine (161.02 ± 4.14 µg/cm²/hr) with an enhancement ratio of 4.56 when carvone was incorporated at a concentration of 10% (w/w) in HPMC gels prepared with 60% (v/v) ethanol. The Fourier transform infrared data indicated that ethanolic solution of carvone increased the transdermal permeability of nimodipine across the rat abdominal skin by partial extraction of lipids in the stratum corneum. The results suggest that 10% (w/w) of carvone in 60% (v/v) ethanol–water, along with HPMC as antinucleating agent may be useful for enhancing the skin permeability of nimodipine from the membrane‐moderated transdermal therapeutic system.