Formulation development of anti-rheumatoid gel of Saraca asoca (Roxb. ) De Wilde hydroalcoholic extract containing eucalyptus oil and peppermint oil as penetration enhancer

Abstract In the present research investigation, various concentrations of hydro-alcoholic extract of Saraca asoca (Roxb.) De Wilde (family: Caesalpinaceae) dried bark and carbopol polymer at different temperature ranges were optimized for the preparation of gel formulation. Natural penetration enhancers, v.i.z., eucalyptus oil and peppermint oil were incorporated separately in the extract based gel formulations to study the rate of drug permeation across egg membrane, using franz diffusion cell. In vitro anti-arthritis potential of the formulations was also studied using inhibition of albumin denaturation, antiproteinase activity and membrane stabilization method. As per the results of current study, it is established that S. asoca dried bark hydroalcoholic extract based gel prepared using peppermint oil as penetration enhancer exhibited good permeation rate of 8.48% at the end of 3 h. The percentage inhibition of proteins by antiproteinase method at concentration of 50 µg/ml was 50.01±1.00% which was close to 53.92±0.99% as shown by the standard drug, Diclofenac. Also, the percent protein inhibition determined using membrane stabilization method was found to be 49.70±1.00%, however, it was 63.32±0.94% for the standard drug, Diclofenac. Hence, it is concluded that peppermint oil may act as a good candidate for the preparation of potent anti-rheumatic gel preparations.

Evaluation of copaiba oil as enhancer of ibuprofen skin permeation

Abstract The administration of medications on the skin through transcutaneous routes is a practice that has been used by mankind for millennia. Some studies have been reporting the use of terpenes and natural oils rich in terpenes as an enhancer of cutaneous penetration. Copaiba oil, due to its rich content of terpenes, presents itself as a great choice of penetration enhancer for drugs administered on the skin. In this study, we developed two cream formulations containing 5% of ibuprofen (IBU) and copaiba oil: IBCO5 and IBCO10 with 5% and 10% of copaiba oil respectively. Ex vivo cutaneous penetration/permeation studies of IBU were performed using pig ear skin as biological membrane in the Franz-type diffusion cells. The steady-state flux of IBU samples, IBCO5 (35.72 ± 6.35) and IBCO10 (29.78 ± 2.41) were significantly higher when compared with control without copaiba oil (10.32 ±1.52) and with a commercial product (14.44 ± 2.39). In the penetration analysis, the amount of IBU found in the samples IBCO5 and IBCO10 was markedly higher in the dermis than epidermis. Our results showed that copaiba oil possesses attracting properties in promoting skin penetration and permeation of IBU when added into cream formulations.

Penetration enhancer for pharmacy prepared compound terbinafine ointment / 药学实践杂志

Objective To screen and identify the penetration enhancer in pharmacy prepared compound terbinafine ointment. Methods In vitro percutaneous penetration test was conducted with vertical Franz diffusion pool. The SD rat's abdomen skin was used for permeable membrane and 60% polyethylene glycol 400-40% saline for receiving liquid to analyze different osmotic promoters. Results The permeability of compound terbinafine ointment was significantly higher with 10% propylene glycol than 15% propylene glycol. The compound terbinafine ointment with 10% propylene glycol was also better than 3% azone in permeability. Conclusion 10% propylene glycol was selected to be the penetration promoter for pharmacy prepared compound terbinafine ointment, which improved the solubility of the drug in the skin.

Application and prospect of alkyl polyglycosides absorption enhancers in drug delivery system / 药学学报

The efficient and safe delivery of drugs to the therapeutic site through the biofilm has traditionally been a difficult and hot topic in the field of drug delivery. In recent years, alkyl polyglycoside (APG) have become ideal penetration enhancers for drug delivery systems because of their high permeability, good safety and biodegradability, which has attracted wide attention of domestic and foreign researchers. In this paper, the physical and chemical properties, characteristics, action mechanism and application of APG in drug delivery system are reviewed, and its application prospect in drug delivery system is prospected.

Formulation And Evaluation Of Benazepril Hydrochloride Transdermal Films For Controlled Drug Release

The current research deals with formulation and evaluation of Benazepril hydrochloride transdermal films, by varying ratios of polymers Eudragit RL100, Eudragit RS100 by film casting technique. Preformulation studies were conducted to check the solubility, melting point and partition coefficient. The eleven formulations were analyzed for physicochemical parameters and drug dissolution potential of transdermal films. All the formulations are transparent with minimum weight variation and uniform thickness. The drug content uniformity of all the formulations vary between 96.84 ± 3.7% to 96.98 ± 1.6% indicate uniform drug distribution. The low water vapour transmission values indicate good water vapour permeation. The folding endurance is between 246 ± 4.60 to 315 ± 4.13 indicates that the transdermal films can withstand rupture. In vitro drug dissolution study indicates maximum amount of drug 96.8% (F2) released in 24 h when compared with marketed formulation 84.81%. The release order follows Fickian diffusion. The formulation F2 was optimized based on drug flux, permeability coefficient and enhancement ratio.

In vivo transdermal permeation-enhancement activity and skin irritation of eucalyptus oil by using microdialysis technique / 中草药

Objective To evaluate the skin irritation of eucalyptus oil and its in vivo transdermal penetration enhancement properties by using the cutaneous microdialysis technique. Methods The CCK-8 assay was used to measure the toxicity of eucalyptus oil on HaCaT cells, and the TEWL values of the rat skin was determined to investigate the effect of eucalyptus oil on the skin integrity and irritation. Ligustrazine and geniposide were chosen as lipophilic and hydrophilic model drugs, respectively, and their microdialysis probe in vivo recoveries were determined using the retrodialysis method. After treatment with eucalyptus oil, the skin pharmacodynamics behaviors of two model drugs were investigated to evaluate its penetration-enhancement activity. Results The cytotoxicity test revealed there IC50 value of eucalyptus oil to HaCaT cells was 2.452 mmol/L, which was significantly higher than that of chemical penetration enhancer Azone (IC50, 0.266 mmol/L). Meanwhile, the eucalyptus oil had a certain impact on the rat skin TEWL values, but it was weaker than Azone, this implied that the eucalyptus oil had a mild skin irritation. The in vivo transdermal microdialysis tests revealed that the enhancement ratios (ER) of ligustrazine and geniposide were 11.40 and 13.79, respectively, indicating that eucalyptus oil could effectively facilitate the transdermal permeation of both of lipophilic and hydrophilic drugs. Although the penetration enhancement property was generally weaker than Azone, the ER value of eucalyptus oil was closely approximate to Azone. Conclusion The eucalyptus oil could promote the transdermal permeation of both lipophilic and hydrophilic drugs with mild skin irritation, which provided the data support for its application in topical preparation.

In vivo transdermal penetration enhancing activity of essential oil from Zanthoxyli Pericarpium by using microdialysis technique / 中国中药杂志

The aim of this paper is to investigate the topical pharmacodynamics behavior of different lipophilic model drugs after treatment with essential oil from Zanthoxyli Pericarpium by using the cutaneous microdialysis technique, and then evaluate its in vivo transdermal penetration enhancing properties. Two traditional Chinese medicine active components, namely tetramethylpyrazine and puerarin, were chosen as lipophilic and hydrophilic model drugs, respectively. Firstly, the concentration difference method was employed to measure the in vitro recovery rate and loss of the microdialysis probe, and the in vivo recoveries of two model drugs were determined by using the retrodialysis method. Secondly, the skin pharmacodynamics behaviors of two model drugs were studied after treatment with different concentrations of the essential oil, and the well-established and standard penetration enhancer Azone was selected as a positive control. It was found that the recovery of microdialysis probe was equal to its loss for two model drugs, with no interaction between drugs in dialysis membranes. The retrodialysis studies revealed that the in vivo recovery of tetramethylpyrazine and puerarin were 59.17%, 19.85%, respectively. The skin pharmacodynamics studies showed that the essential oil could facilitate the transdermal absorption of tetramethylpyrazine in a concentration-dependent manner, and the enhancement ratio (ER) for 5% essential oil was 98.64, which was higher than that of the optimum concentration of Azone (3% Azone, ER=89.11). Meanwhile, the Zanthoxyli Pericarpium could effectively promote the transdermal permeation of the puerarin in a concentration-dependent manner. Hence, this study further confirmed that the Zanthoxyli Pericarpium had excellent penetration-enhancing activity as a natural transdermal penetration enhancer, providing data support for its application in traditional Chinese medicine external preparations.

Effect of wintergreen oil on in vitro transdermal permeation of osthole and geniposide / 中国中药杂志

The aim of this study was to investigate the transdermal penetration enhancement effect of wintergreen oil and its action mechanisms. The in vitro transdermal tests were carried out to study the transdermal penetration enhancement effect of wintergreen oil by using osthole and geniposide as the lipophilic and hydriphilic model drugs. Fourier-transform infrared spectroscopy was used to investigate the effect of wintergreen oil on the molecular structure of rat stratum corneum, and the scanning electron microscope was employed to observe the change of rat skin surface after treatment by the oil. The wintergreen oil at proper concentrations could effectively promote the transdermal permeation of osthole and geniposide, and exhibited better penetration-enhancing activity for the lipophilic osthole, close to the commonly used classical penetration enhancer azone. The infrared spectroscopy study and scanning electron microscope showed that wintergreen oil mainly acted on the stratum corneum lipids, reduced dense stratum corneum, and reduced the skin barrier function. Thus, the wintergreen oil could effectively facilitate the transdermal absorption of the lipophilic and hydrophilic drugs, resulting from the lowed skin barrier function.

Optimization of the dose of penetration enhancers in celecoxib gel by factorial design / 中国药学杂志

OBJECTIVE: To optimize the formula of celecoxib gel by studying the effects of different doses of penetration enhancers on the penetration of celecoxib through skin in vitro. METHODS: With sodium alginate as the gel base, factorial design method was used to choose the optimal formula of penetration enhancers among four different formulas to prepare celecoxib gels. The release rate of celecoxib in the release media was detected by modified Franz diffusion cells method, and the steady percutaneous speed (J), permeability coefficient (Kp) and the accumulative permeation quantity (Q) in 12 h were calculated. RESULTS: The accumulative permeation quantity (Q) in 12 h of celecoxib from the gels made with the four different formulas were 27.93, 25.12, 18.79 and 19.35 μg·cm-2, respectively. The gel with 1% azone and 1% menthol as penetration enhancers had the maximum Q value, 27.93 μg· cm-2, its penetration process conformed to Higuchi equation, and the steady percutaneous speed (J) and permeability coefficient(Kp) were also higher than the other three experimental groups. CONCLUSION: With sodium alginate as the gel base, azone and menthol have a synergistic effect on the percutaneous penetration of celecoxib gels, and the best formula is 1% azone and 1% menthol.

New Techniques for the Evaluation of Penetration Enhancers / 中国药学杂志

Penetration enhancers (PEs) are commonly used for improving bioavailability of transdermal drug delivery formulations. In the present paper, the new techniques to investigate the penetration enhancement ability, penetration enhancement mechanism and skin safety of PEs were intensively reviewed. The trends of PE research include high throughput evaluation of penetration enhancement ability, micro-molecular research of penetration enhancement mechanism and quantitative characterization of skin safety. Emergence of new techniques provides technical support which is faster, more comprehensive and reliable for the selection and research of penetration enhancers in future.

Optimization of the Penetration Enhancers for Xiaochuan Emplastrum / 医药导报

Objective To investigate and optimize the penetration enhancers of Xiaochuan emplastrum. Methods Franz diffusion cell was employed with isolated mice abdominal skin as barrier. The accumulating osmotic quantity per unit area and penetrating absorption rate of Sinapine thiocyanate were determinated by HPLC method. The penetration enhancers were selected and the ratio was determined. Results Combination of azone and propylene glycol were better than other kinds of enhancers for penetration effect, the ratio of propylene glycol and azone was 2:1. Dosage of azone and propylene glycol was finally optimized to 5% of prescription dosage.Under these conditions, cumulative permeation quantity of Sinapine thiocyanate was 369.59 μg·(cm2)-1, penetration rate of Sinapine thiocyanate was 14.19 μg·(cm2)-1·h-1 and enhancing rate was 3.19. Conclusion The ratio of propylene glycol and azone was 2:1,dosage of azone and propylene glycol was 5% of prescription dosage, which has a significant penetration effect and can be used as the penetration enhancer of Xiaochuan emplastrum.

Optimization of the Penetration Enhancers for Xiaochuan Emplastrum / 医药导报

Objective To investigate and optimize the penetration enhancers of Xiaochuan emplastrum. Methods Franz diffusion cell was employed with isolated mice abdominal skin as barrier. The accumulating osmotic quantity per unit area and penetrating absorption rate of Sinapine thiocyanate were determinated by HPLC method. The penetration enhancers were selected and the ratio was determined. Results Combination of azone and propylene glycol were better than other kinds of enhancers for penetration effect, the ratio of propylene glycol and azone was 2:1. Dosage of azone and propylene glycol was finally optimized to 5% of prescription dosage.Under these conditions, cumulative permeation quantity of Sinapine thiocyanate was 369.59 μg·(cm2)-1, penetration rate of Sinapine thiocyanate was 14.19 μg·(cm2)-1·h-1 and enhancing rate was 3.19. Conclusion The ratio of propylene glycol and azone was 2:1,dosage of azone and propylene glycol was 5% of prescription dosage, which has a significant penetration effect and can be used as the penetration enhancer of Xiaochuan emplastrum.

Comparison of essential oil from Mentha haplocalyx and menthol used as penetration enhancers / 中国中药杂志

The aim of this paper was to investigate and compare the penetration-enhancing characteristics of menthol and essential oil from Mentha haplocalyx(M.haplocalyx oil) on the transdermal absorption of the complex traditional Chinese medicine(TCM) components. A series of TCM components were selected as model drugs based on their lipophilicity (logP value), namely osthole(OT, logP=3.85), tetramethylpyrazine(TMP, logP=2.34), ferulic acid(FA, logP=1.26), puerarin(PR, logP=-0.35) and geniposide(GP, logP=-1.01), in order to simply and characterize the TCM complex components system. Transdermal experiment in vitro was employed to investigate and compare the penetration-enhancing characteristics of menthol and M.haplocalyx oil on the transdermal absorption of these model drugs. Meanwhile, Fourier transform infrared spectroscopy(FTIR) was used to further compare the effect of menthol and M. haplocalyx oil on the molecular structure of stratum corneum(SC). The results showed that both of menthol and M.haplocalyx oil at proper concentration could promote the transdermal absorption of the selected model drugs. After application of menthol, the drug logP values gradually tended to have negative linear relationship with the logarithm of penetration enhancement ratio(ER); while after application of M.haplocalyx oil, the logP values tended to have parabolic relationship with the logarithm of ER. However, both menthol and M.haplocalyx oil exhibited higher efficiency for the drugs with relative low lgP value(ie hydrophilic drugs), with similar penetration-enhancing characteristics between these two. Infrared spectroscopy results showed that menthol and M.haplocalyx oil could affect the skin barrier functions mainly via stratum corneum lipids, with similar effect intensity, and this was consistent with the results of transdermal experiment in vitro. Thus, Menthol had similar penetration-enhancing characteristics with M.haplocalyx oil, and had same effect on the SC molecular structure. Therefore, as transdermal penetration enhancer, the menthol with single composition could be considered to replace M.haplocalyx oil with complex compositions.

Effects of different penetration enhancers on pharmacokinetics of active components in Xiangfu Siwu transdermal patches / 中国中药杂志

To study the effect of different penetration enhancers on the pharmacokinetic characters of six active components in Xiangfu Siwu transdermal patch (XBW) and optimize the best penetration enhancers. During the experiment, the patches containing different penetration enhancers were stuck on the rat's skin, and then the blood samples were acquired at different time points. Six active components in plasma were determined by UPLC-MS/MS. The main pharmacokinetic parameters were calculated with DAS software package. The total factor scores (F) of the plasma concentrations of six components at every time point in different groups were calculated using principle component analysis, and the areas under F versus time curves (AUCF-t) were employed to be the indexes for selecting penetration enhancers. The results demonstrated that compared with the control group, the AUCF-t from other groups increased prominently and furthermore, 5% menthol manifested the best effect. In this research, 5% menthol could remarkably promote the percutaneous penetration effect of the six active compounds in XBW, and it could provide a scientific basis for the preparation research of XBW.

Effect of Different Penetration Enhancers on Percutaneous Absorption of Xiaoyan Runma Mucilage / 医药导报

Objective To investigate the effects of different penetration enhancers on percutaneous absorption of Xiaoyan Runma mucilage in vitro, and to improve the curative efficacy of this mucilages through selection of the effective penetration enhancers. Methods Xiaoyan Runma mucilage was prepared with different penetration enhancers. An intelligent permeability instrument was used for in vitro percutaneous absorption test of rats , with isolated mice abdomen skin serving as in vitro transdermal barrier and saline isotonic solution as receptor fluid. Then the contents of lidocaine hydrochloride in receptors were determined by HPLC.The accumulative transit dose (Q) and percutaneous permeability (J) within 12 h were calculated and compared with those of mucilage without any enhancer. Results With Q value serving as an index, different enhancers had different promote permeation effects on Xiaoyan Runma mucilage, and the effects in descending order were as follows:4% azone [(222.75±3.4) μg?(cm2)-1]>2% azone[(207.42±5.1) μg?(cm2)-1]>3% menthol [(183.38±4.9) μg?(cm2)-1]>5%menthol [(160.82±5.4) μg?(cm2)-1]>2% azone+3% menthol [(151.25±5.5) μg?(cm2)-1]>2% azone+5% isopropyl myristate [(127.26±7.1) μg?(cm2)-1]>2% oleic acid [(125.16±6.5) μg?(cm2)-1]>no enhancer [(109.82±8.2)μg?(cm2)-1].4% azone was the best penetration enhancer for the mucilage delivery in vitro, with Q and J value as [(222.75± 3.4)μg?( cm2 )-1 ] and 19. 896 μg?( cm2 )-1?h-1 , respectively, which was 2. 08 times those of mucilages without any enhancer. Conclusion Being as a transdermal absorption enhancer of Xiaoyan Runma mucilage, 4% azone has the best effect. This study can provide the optimal formulation for transdermal delivery system of Xiaoyan Runma mucilage.

Effects of Borneol on Membrane Fluidity and Membrane Potential of HaCaT Cell / 中国中医药信息杂志

Objective To investigate the action mode of borneol on activity of epidermal skin;To investigate action mode of borneol as penetration enhancer. Methods The well-established and standard penetration enhancer Azone was employed as a positive control in this study. The cytotoxicities of borneol and Azone on HaCaT cells were detected by CCK-8 assay, and their half 50% inhibitory concentrations (IC50) were calculated. The fluorescence recovery after photo bleaching was employed to investigate the effect of borneol and Azone on membrane fluidity, and the flow cytometer was used to monitor the changes of membrane potential of HaCaT cell after treated with these penetration enhancers. Results The IC50 values of borneol and Azone were 2.826 , 0.172 mmol/L, respectively. Borneol could significantly improve the membrane fluidity in a concentration-dependent manner, and effectively decrease the membrane potential of HaCaT cell, which exhibited the performances similar to those of Azone. Conclusion The penetration enhancement mechanism of borneol was associated with the concentrations of Ca2+ in keratinocytes, which changes the membrane fluidity and membrane potential of HaCaT cell.

Research Progress of Penetration Enhancers / 中国中医药信息杂志

Penetration enhancers are substances to improve the rate or amount of transdermal permeation which is an important factor in transdermal drug delivery systems (TDDS). Recent researches have found that some of the new penetration enhancers have a higher penetration-effect, little irritation, fewer adverse reactions, and stable properties. In this article, domestic and foreign research reports on penetration enhancers have been collected and summarized. The research progress of penetration enhancers were reviewed, with a purpose to provide a reference for reasonable selection of penetration enhancers.

Transdermal Penetration Enhancement of Arginine Oligomer-chitosan on Tinidazole in vitro and in vivo / 中国药师

Objective:To study the in vitro and in vivo transdermal enhancement of one kind of arginine oligomer-chitosan ( CS-R9). Methods: In vitro mouse skin as the barrier, Franz diffusion cells were used to study the transdermal property of tinidazole ( TNZ) solution in vitro enhanced by CS-R9 using TNZ solution as the negative control and TNZ solution with Azone as the positive control. The rats were randomly divided into three groups, TNZ solution group ( the negative group) , TNZ solution with Azone group (the positive group) and TNZ solution with CS-R9 group. At the predetermined time intervals, 0. 5 ml blood was withdrawn from the rats and TNZ concentration was detected by HPLC to evaluate the enhancement of CS-R9 on TNZ in vivo. Results:Compared with the negative group, CS-R9 had significant enhancement on TNZ trandermal penetration in vitro(P 0. 05). The in vivo results showed CS-R9 exhibited similar transdermal enhancement on TNZ as Azone at the same concentration (P>0. 05), and CS-R9 had sustalned-release property. Conclusion: CS-R9 has promising transdermal en-hancement on TNZ, which is valuable to be studied further.

Effect of novel terpenes penetration enhancer on in-vitro percutaneous penetration of propranolol hydrochloride hydrogel / 中国药学杂志

OBJECTIVE: To investigate the effects of different novel terpenes penetration enhancers and their combinations on percutaneous absorption of propranolol hydrochloride hydrogel and screen the best penetration enhancers so as to increase the cumulative permeation quantity in the target site. METHODS: The percutaneous permeation experiment was carried out with modified Franz-type diffusion cell with isolated piglet skin as the barrier. The effects of the types, concentrations, and combinations of penetration enhancers on the transdermal penetration of propranolol hydrochloride hydrogel were compared using cumulative permeation quantity (Q) and enhancing rate (ER) as indexes. RESULTS: The effectiveness of terpenes was found to be the optimal at concentration of 3% in the following order; farnesol > L-menthol > nerolidol > tetrahydrogeraniol > 1, 4-cineole≈geraniol > limonene > anethole > borneol > negative control > dipotassium glycyrrhizic acid. The release profiles from the hydrogel formulations obeyed zero-order kinetics. Farnesol, L-menthol, and nerolidol effectively promoted the percutaneous penetration of propranolol hydrochloride over the concentration range of 1% - 5%. The enhancement ratio was the highest at 3% and decreased if the concentration increased to 5%. Significant synergism was observed when the enhancers were used in combination (P < 0.05), while there was an antagonistic effect when 3% farnesol or 3% L-menthol was combined with propylene glycol (P < 0.05). CONCLUSION: The percutaneous absorption of propranolol hydrochloride is increased by the terpenes enhancers and reached the peak value with 3% farnesol plus 10% isopropanol. These findings provide a basis for the further transdermal delivery studies of propranolol hydrochloride.

Effects of three kinds of cyclodextrin on in vitro corneal penetration of curcumin / 中草药

Objective: To study the effects of β-cyclodextrin (β-CD), hydroxypropyl-β-CD (HP-β-CD), and sulfobutyl-ether-β-CD (SBE-β-CD) on in vitro corneal penetration of curcumin. Methods: Improved Franz-cells were used for the corneal diffusion test and the cumulative permeation quantity of curcumin in the corneal was determined by HPLC. Results: β-CD at 0.02%, 0.04%, 0.06%, and 0.08% improved the apparent permeability coefficient as much as 1.06, 1.03, 1.00, and 0.95 times. HP-β-CD at 0.02%, 0.04%, 0.06%, and 0.08% improved the apparent permeability coefficient as much as 1.16, 1.19, 1.17, and 1.12 times; HP-β-CD at 0.04% and 0.06% there was a significant deference compared with the control group (P < 0.05). SBE-β-CD at 0.02%, 0.04%, 0.06%, and 0.08% improved apparently the permeability coefficient as much as 1.06, 1.23, 1.08, and 0.90 times. SBE-β-CD at 0.04% there was a significant deference compared with the control group (P < 0.05). SBE-β-CD at 0.06% as penetration enhancer, release curve accorded with zero order release equation (r = 0.9978). The average of the corneal hydration is 81.7%. Conclusion: HP-β-CD at 0.04% and 0.06% could improve the apparent permeability coefficient as much as 1.19 and 1.17 times (P < 0.05). SBE-β-CD at 0.04% could improve the apparent permeability coefficient as much as 1.23 times (P < 0.05). SBE-β-CD as corneal penetration enhancers can release safely and effectively. As corneal penetration enhancers, those three kinds of cyclodextrin are without irritation to corneal.