Transdermal delivery of hydrocortisone from eucalyptus oil microemulsion: effects of cosurfactants

This study investigated the effects of cosurfactants on the transdermal delivery of hydrocortisone (model drug) from eucalyptus oil microemulsion. Eucalyptus oil which was successfully employed for steroidal drugs was used as the oil. Tween 80 which was readily miscible with eucalyptus oil was used as surfactant. Ethanol, isopropanol and propylene glycol which are relatively tolerable by the skin were employed as cosurfactants. Pseudo-ternary phase diagrams were constructed in the presence and absence of cosurfactants. Microemulsion formulations containing 20% oil, 20% water and 60% of either Tween 80 or 1:1 surfactant/cosurfactant mixture were compared. Incorporation of cosurfactants expanded the microemulsion zone. The cosurfactant free microemulsion was viscous showing pseudo-plastic flow. The cosurfactant containing preparations were less viscous with Newtonian flow. The drug loading and release rate were increased in the presence of cosurfactants with the release depending on the viscosity. Incorporation of hydrocortisone in microemulsion increased the transdermal flux compared to saturated aqueous solution. The presence of cosurfactants increased the transdermal drug flux compared to the cosurfactant free formulation. Ethanol produced the greatest effect followed by propylene glycol and isopropanol. The presence of cosurfactant and its type can thus affect both the phase behavior and the transdermal delivery potential of microemulsion.     

Shaving effects on percutaneous penetration: clinical implications

Context: Human/animal shaving biology.

Objective: To assess the effect of shaving on percutaneous penetration and skin function.

Methods: We screened 500+publications in Pub Med, Scopus, Cochrane Library and pertinent journals out of which only 17 were deemed relevant. Terms for searches included shaving and skin, percutaneous penetration and shaving, skin absorption and shaving, absorption of dyes and shaving, skin penetration, effects of shaving and absorption, shave and dyes, axillary shaving and stratum corneum, shaving and breast cancer, shaving and infections, etc.

Result: Shaving appears to have an exaggerated effect on percutaneous absorption; however, some studies do not support this evidence.

Conclusion: Shaving enhances percutaneous penetration of some chemicals; however this effect is species and chemical specific. Further investigations of chemicals of varying physio-chemical properties are mandated before a generalized theory can be promulgated.     

Assessment of the percutaneous penetration of cisplatin: The effect of monoolein and the drug skin penetration pathway

It was intended to examine the in vitro penetration of cisplatin (CIS) through porcine skin in the presence of different concentrations of monoolein (MO) as well as to verify the main barrier for CIS skin penetration. In vitro skin penetration of CIS was studied from propylene glycol (PG) solutions containing 0%, 5%, 10%, and 20% of MO using Franz-type diffusion cell and porcine ear skin. Pretreatment experiments with MO and experiments with skin without stratum corneum (SC) were also carried out. Skin penetration studies of CIS showed that the presence of MO doubled the drug permeation through the intact skin. However, permeation studies through the skin without SC caused only a small enhancement of CIS permeation compared to intact skin. Moreover, pretreatment of skin with MO formulations did not show any significant increase in the flux of the drug. In conclusion, MO did not act as a real penetration enhancer for CIS, but it increased the drug partition to the receptor solution improving CIS transdermal permeation. The absence of improvement in drug permeation by MO pretreatment and by the removal of SC indicates that the SC is not the main barrier for the permeation of the metal coordination compound.     

Enhancing effect of alpha-monoisostearyl glyceryl ether on the percutaneous penetration of indomethacin through excised rat skin.

The enhancing effect of alpha-monoisostearyl glyseryl ether (GE-IS) on the percutaneous penetration of indomethacin (IM) from test solutions in propylene glycol (PG) was investigated using the excised abdominal skin of rats in vitro. The percutaneous penetration of IM into diffusion cells was significantly increased in the presence of 0.2% or 1% (w/w) GE-IS compared with enhancer-free PG solution. Permeation parameters of IM, such as lag time and permeability coefficient, revealed that GE-IS significantly augmented the percutaneous penetration of IM from PG. These results strongly suggested that GE-IS functions as a penetration enhancer of IM through rat skin. To elucidate the mode of action of GE-IS as a penetration enhancer, the solubility of IM in the test solution and the percutaneous penetration of IM through damaged skin from which the stratum corneum had been stripped were investigated. The results suggested that GE-IS acts directly on the stratum corneum and alters the permeability of the skin.     

桉油对丙酸氮倍他索乳膏经皮渗透和吸收的作用

目的：考察促进剂桉油对丙酸氯倍他索（CBT）乳膏经皮渗透的促进作用,通过比较透过量和皮层中量,分析在该制剂中是否透合使用桉油,方法：采用直立式扩散池,考察了桉油在0．5％,1．0％,5．0％浓度下0．05％CBT乳膏经皮渗透2,4,6,8,10,24h后单位面积累积透过量Q(ug.cm^-2)和稳态透皮流量J（ug.cm^-2.h^-1);HPLC法测定经皮渗透24h后每克皮肤组织中CBT的量D（ug.g^-1),结果：4种浓度的桉油均显著促进CBT乳膏透皮吸收（P＜0．01）,其J值约是对照组的3－5倍（P＜0．01）,随浓度增加,陂层量D并不随之相应增加,结论：桉油可加快CBT经皮渗透速度,也能增加皮层中CBT量,但有饱和性,建议CBT 乳膏膏以少加（＜50％）或不加桉油为好。     

Evaluation of nicotinamide microemulsion on the skin penetration enhancement

This study purposed to evaluate a microemulsion containing nicotinamide for its characteristics, stability, and skin penetration and retention comparing with a solution of nicotinamide in 2:1 mixture of water and isopropyl alcohol (IPA). The microemulsion system was composed of 1:1 mixture of Span80 and Tween80 as a surfactant mixture, isopropyl palmitate (IPP) as an oil phase, and 2:1 mixture of water and IPA as an aqueous phase. Nicotinamide microemulsion was prepared by dissolving the active in the aqueous phase before simply mixing with the other components. It was determined for its characteristics and stability under various conditions. The skin penetration and retention studies of nicotinamide microemulsion and solution were performed by modified Franz diffusion cells, using newborn pig skin as the membrane. The results showed that nicotinamide microemulsion could be obtained as clear yellowish liquid, was water-in-oil (w/o) type, possessed Newtonian flow, and exhibited physicochemical stability when kept at 4?°C and room temperature (≈30?±?2?°C) during 3 months. From the skin penetration data, the microemulsion could enhance the skin penetration of nicotinamide comparing with the solution. Additionally, nicotinamide microemulsion could provide much higher amount of skin retention than that of skin penetration, resulting in suitability for a cosmeceutical product.     

大豆油、水分和铁对大豆磷脂酸值和碘值的影响

目的寻求克服大豆磷脂酸败变质的措施。方法将数量不等的大豆油、水、铁 (三氧化二铁 )加到大豆磷脂中放置一年 ,观察大豆磷脂的酸值、碘值变化。结果当大豆磷脂中含大豆油超过 10 %时 ,酸值增加明显变缓 ;水分和铁促进大豆磷脂酸值上升。结论大豆磷脂在含大豆油 10 %以上 ,含水 1%以下 ,不含铁时比较稳定。     

Transdermal delivery of paracetamol for paediatric use: effects of vehicle formulations on the percutaneous penetration

Paracetamol is a safe and effective analgesic and antipyretic agent, and is one of the most widely used medications for infants and children. The formulations currently available have been designed for oral and rectal administration. However, they are not practical in young patients with vomiting and diarrhoea, or in those who refuse to take the full dose. An alternative route of administration would be a significant contribution to the paediatric pharmacopoeia. The aim of this study was to develop a new transdermal system for optional therapeutic administration of paracetamol in infants and children. In-vivo studies were carried out in animals using a transdermal system of high-loaded, soluble paracetamol in a hydrogel patch, which was also tested in-vitro for 8 h. Although the beneficial contribution of glyceryl oleate to the transdermal penetration of paracetamol seemed to be significant in-vitro, it was shown to be insufficient in-vivo. To improve the penetration of the drug, 4% PEG-40 stearate and 10% ethanol were incorporated as absorption enhancers into the dermal patches. A few hours after application of the improved patches to rats, plasma drug concentrations were elevated to levels comparable with those obtained after oral and subcutaneous administration of a high dose of paracetamol. Since plasma drug concentrations did not reach a constant steady state (as a peak or plateau) during the short-term animal experiments, longer pharmacokinetic studies in conscious animals are necessary.     

Effect of pretreatment by cardamom oil on in vitro percutaneous penetration of piroxicam gel

The effect of pretreatment by the penetration enhancer, cardamom oil, on the percutaneous penetration of piroxicam from gel through rabbit abdominal skin was investigated using an in vitro technique. The flux and the cumulative amount (at the 48th h) after 1 h pretreatment with 10% cardamom oil in three vehicle systems (alcohol, alcohol/pH 5.8 buffer and alcohol/pH 7.4 buffer) were higher than that of nonpretreatment, and were similar to that of 3 or 6 h pretreatment. A specific correlation between the flux of piroxicam and the pretreatment period was found. Compared to the lag time of skin penetration of piroxicam for nonpretreatment, the lag time for pretreatment was remarkably diminished. The penetration index (PI) of piroxicam after 1 h pretreatment with 10% cardamom oil in alcohol/pH 7.4 buffer (50/40) was about 340.9-fold higher than that of nonpretreatment. In contrast to previous results. 1 h pretreatment with 10% cardamom oil in alcohol had no significant enhancing effect on the percutaneous penetration of piroxicam from gel dosage form. From these results, the alcohol proportion of the vehicle system was the more effective factor for penetration index.     

The effect of surfactants on the skin penetration of diazepam

The percutaneous permeation of diazepam was investigated in rat skin after application of a water-propylene glycol (50:50% v/v) using a diffusion cell technique. The effect of various surfactants (sodium lauryl sulfate (SLS), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride or Tween 80) with different concentrations on skin permeability were evaluated. Flux, K(p), lag time and enhancement ratios (ERs) of diazepam were measured over 10 h and compared with control sample (containing no surfactant). Furthermore, diazepam solubility in presence of surfactants was determined. The in vitro permeation experiments with rat skin revealed that the surfactant enhancers varied in their ability to enhance the flux of diazepam. Benzalkonium chloride which possessed the highest lipophilicity (logP=1.9) among cationic surfactants provided the greatest enhancement for diazepam flux (7.98-fold over control). CTAB (logP<1) at a concentration of 1% w/w exhibited no significant increase in flux of diazepam compared to control (1.16-fold over control). The results also showed that the highest ER was obtained in presence of 1% w/w surfactant with the exception of SLS and CTAB. The increase in flux at low enhancer concentrations is normally attributed to the ability of the surfactant molecules to penetrate the skin and increase its permeability. Reduction in the rate of transport of the drug present in enhancer systems beyond 1% w/w is attributed to the ability of the surfactant to form micelles and is normally observed only if interaction between micelle and the drug occurs. The results showed that the nature of enhancer greatly influences cutaneous barrier impairment.     

Insights into the percutaneous penetration of antidiabetic agents

It has been suggested that destruction of β cells through apoptosis leads to type 1 diabetes (T1DM) while type 2 diabetes (T2DM) is caused mainly by increased insulin resistance. Several therapeutic agents are available for the management of diabetes. While researchers continue to investigate disease-modifying compounds, it is also important to develop alternative drug delivery systems for existing medications with the goal of modulating bioavailability and/or pharmacokinetic half-life. Transdermal drug delivery offers a number of advantages including improved compliance, lack of gastric irritation and the possibility of altering bioavailability and and/or half-life. In this review, the percutaneous penetration of antidiabetic agents is discussed. This is particularly significant given the fact that several compounds with hypoglycemic properties are being developed by academic research laboratories and the biotechnological industry. Microneedles, sonophoresis, chemical penetration enhancers and iontophoresis are some of the approaches used for the transdermal delivery of antidiabetic agents. It is anticipated that with more research, some of these transdermal drug delivery systems will be incorporated into clinical practice.     

Development of an oral microemulsion formulation of alendronate: effects of oil and co-surfactant type on phase behaviour

This study aimed to prepare a water-in-oil microemulsion formulation of alendronate. Pseudo-ternary phase diagrams were constructed by using different oils and co-surfactants. The final formulation was decided to be prepared with Captex 200, lecithin, propylene glycol and bidistilled water. Rheological behaviour, phase stability and type of the microemulsion formulation were investigated by Brookfield viscosimeter, centrifugation test and dye method, consequently. Phase behaviour of the formulation was found to be Newtonian. No precipitation was observed in the stressed conditions and formulation was W/O. The physical characterization of the formulation (physical appearance, viscosity, refractive index, conductivity, density and turbidity) was investigated at 4 degrees C and 25 degrees C during 6 months while droplet size was investigated for 3 months. Droplet size of the formulation was between 224-280 nm while viscosity was between 89.9-99.5 mPa.S. The release of alendronate from the microemulsion formulation was examined by dialysis method and found to be 97.2% at the end of 7 h. None of the parameters except refractive index changed significantly during the determined periods. This study succeeded in preparing a stable microemulsion formulation of alendronate.     

氯仿、乙醇作为溶剂测定大豆磷脂酸值

目的建立一种测定各种大豆磷脂酸值的方法。方法用氯仿乙醇 ( 2∶1 ,V∶V)作为溶剂溶解大豆磷脂后 ,用 0 1mol/L氢氧化钠滴定 ,并同药典法进行了对比。结果本方法的精密度RSD为0 3%～ 1 8% ,《中华人民共和国药典》法为 0 9%～ 7 3% ;本方法的回收率为 96 5 %～ 98 5 % ,《中华人民共和国药典》法为 78 5 %～ 97 0 %。结论用氯仿乙醇 ( 2∶1 ,V∶V)作为溶剂可适用于各种磷脂酸值的测定     

Design of novel prodrugs for the enhancement of the transdermal penetration of indomethacin

A series of esters of indomethacin containing tertiary amine functional groups and designed for transdermal delivery were synthesized. The rates of chemical hydrolysis of all the esters in pH 7.4 phosphate buffer were determined. For N,N-diethylaminopropyl N-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indole acetate (ester 4), the rates of chemical hydrolysis in pH 5.5–11.25 buffers were investigated in detail. Ester 4 was chemically stable and had a higher n-octanol/water partition coefficient and a greater solubility in water at pH 7.4 than indomethacin. Furthermore, the rate of transdermal penetration of ester 4 through cadaver skin in Franz cells was found to be more than 10-times faster than that of indomethacin itself. Ester 4 was found to possess surface-active properties (CMC = 0.5 mg/ml). Assuming that micelles cannot penetrate biologic membranes, a corrected permeability coefficient was calculated for ester 4 using only the monomer concentration. This value, 3.6 × 10⁻² cm/h, was 100-times greater than that of indomethacin. These results suggest that prodrugs with structures similar to that of ester 4 may be useful for enhancing transdermal penetration of other carboxylic acid-containing anti-inflammatory agents.