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AIM: To compare the effect of azone and menthol by using the 5-fluorouracil (5-FU) as drug model, and explore the mix effect of the two transdermal enhancers. METHODS: The test acts on the self-made instrument. After the test, calculate the total amount of the drug which has permeate through the skin was calculated and the mixed effect of azone and menthol was estimated by multiple quantity method.RESULTS: Both azone and menthol of concentrations of 0.25%, 0.50%, 1.00% and 2.00% had significant penetration promoting effect on 5-fluorouracil, which were significantly different from the control group (P<0.01). No synergistic effect was detected when evaluating the combined effect of the two drugs by multiple dose method. CONCLUSION: Both azone and menthol have promotion effect on 5-fluorouracil, but the combined use of the two drugs of same concentration show no synergistic effect.
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Objective: To establish a determination method for kinds of chemical components of iridoids in the roots of Gentiana crassicaulis in transdermal absorption liquid, and research its transdermal permeability, so as to provide scientific basis for transdermal delivery system, clinical medication and reform of the traditional forms of G. crassicaulis. Methods: Based on the results of the previous investigation, in this paper, using the roots of G. crassicaulis as the research subject, a certain concentration solution of G. crassicaulis extract was prepared by the alcohol extraction method. Three kinds of common penetration enhancers, azone, borneol and propylene glycol were used. The effects of single penetration enhancer and dual compound penetration enhancers on the transdermal penetration of five kinds of chemical components of loganic acid, shanzhiside methyl ester, swertimarin, gentiopicroside and sweroside in vitro and the three kinds of chemical components of gentiopicroside, loganic acid and swertimarin in vivo were quantitatively studied by the method of HPLC to investigate the transdermal permeability of G. crassicaulis extract in mice skin model. Results: According to the experimental results, compared to the control group, penetration enhancers significantly increased the absorption of five chemical components of G. crassicaulis in vitro. Transdermal absorption rates (J) of loganic acid, shanzhiside methyl ester, swertimarin, gentiopicroside and sweroside were 12.306 0, 1.248 8, 4.187 5, 153.030 0 and 5.012 6 μg/(cm2∙h), respectively. The transdermal enhancer effects of A (5% azone), B (5% borneol), C (5% propylene glycol), A + B (2.5% azone and 2.5% borneol), A + C (2.5% azone and 2.5% propylene glycol), A + C (2.5% borneol and 2.5% propylene glycol) were 9.73, 2.57, 13.94, 15.92 and 8.08 times faster than the control group, respectively. Among these, the group of A + C had a marked osmotic enhancer effect in vitro. In comparison with the control group, the in vivo percutaneous penetration test indicated that the dual compound penetration enhancers of 2.5% azone and 2.5% propylene glycol had a marked effect for the permeability enhancement. Conclusion: This study showed azone and propylene glycol significantly promoted the percutaneous penetration effect of loganic acid, shanzhiside methyl ester, swertimarin, gentiopicroside and sweroside of G. crassicaulis, and this study laid a foundation for the quality control of percutaneous drug delivery preparation of G. crassicaulis.
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Objective To optimize the matrix formulation for Shaofu Zhuyu Cataplasm (SZC) by Plackett-Burman design combined with Box-Behnken response surface method and study its transdermal permeation properties in vitro. Methods In this paper, the appearance description, initial bonding strength, endurance bonding strength, and peel strength were taken as indexes. Based on the result of a single factor experiment, the formula for the SZC was optimized by Plackett-Burman combined with Box-Behnken method. Franz diffusing cells method was chosen to investigate the tansdermal infiltration capacity of SZC with different dosage penetration enhancers of azone in vitro, taking ferulic acid, paeoniflorin, isorhamnetin-3-O-neohesperidin, and typhaneoside as index components. Results NP-700, tartaric acid and kaolin had significant effects on the properties of SZC. The optimal ratio of the prescription was as follows: NP-700-tartaric acid-kaolin (2.42:0.16:0.96). The promoting effect of 3% concentration for index component was better, and the transdermal rates of ferulic acid, paeoniflorin, isorhamnetin-3-O-neohesperidin, and typhaneoside were 6.889 4, 1.917 4, 0.852 0, and 0.893 7 μg/(cm2∙h), respectively. Conclusion The SZC was uniform, without residual behavior in application. And it had a good release and transdermal properties, and transdermal actions were consistent with zero-order kinetics.
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AIM To study the effect of azone on transdermal absorption of 6-gingerol.METHODS In vitro transdermal diffusion test was performed by TP-6 horizontal diffusion pool.In vitro rat skins were selected as permeation barrier,the effects of different concentrations of ethanol and azone on permeation performance of 6-gingerol were investigated.RESULTS Both 30％ ethanol and 3％ azone contributed to the significant permeation enhancement of 6-gingerol.CONCLUSION This research can provide reference for the preparation of transdermal drug delivery systems containing 6-gingerol.
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OBJECTIVE: To screen pressure sensitive adhesive system and penetration enhancer of rutaecarpine transdermal patch. METHODS: The patch was prepared by solvent evaporation method. The ratio between pressure sensitive adhesive (Eudragit E100), crosslinking agent (succinic acid) and plasticizer (dibutyl sebacate) of the rutaecarpine patch were screened through Box-Behnken design by using adhesion (stick power, shear strength, peel force) as the index. The ratio between pressure sensitive adhesives and chemical enhancers (azone and oleic acid) were screened by adhesion and permeation experiments in vitro using custom design, which were carried out by using improved Franz diffusion cells through excised mice skin. RESULTS: The optimized formulation of rutaecarpine transdermal patch consisted of 83% pressure sensitive adhesives (63.5% Eudragit E100, 5.5% succinic acid, 14% dibutyl sebacate), 10% azone, 6.4% oleic acid and 0.6% rutaecarpine. The stick power, shear strength, and peel force of the patch were 15 steel balls, (10.97 ± 0.32) h and (0.16 ± 0.02) kN•M-1, respectively. The cumulative permeation amount and permeation rate of the patch were (29.71 ± 1.19) μg•cm-2 and (1.36 ± 0.10) μg•cm -2•h -1, respectively. CONCLUSION: The optimized rutaecarpine patch show increased permeation and appropriate adhesion. This study provides the basis for future research.
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Objective: To screen the best transdermal enhancers of naringenin in Premna fulva extract. Methods: Using abdominal skin of rats as experimental barrier, the in vitro percutaneous absorption experiment was established by modified Franz diffusion cell method. The cumulative infiltration and permeation rate of naringenin in three different penetration enhancers were determined by HPLC. Results: The borneol, menthol, and azone could enhance transdermal absorption of naringenin in different degree. Several penetration enhancers were increased in the following order: borneol > menthol > azone. The average percutaneous rate of naringenin was 0.136 8 mg/(cm2∙h), using 5% borneol as penetration enhancer. Conclusion: The 5% borneol is an effective transdermal enhancer for naringenin in P. fulva extract.
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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.
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This experiment was aimed to screen the absorption enhancer for intranasal administration preparations of paeoniflorin. In this study, HPLC method for determination of paeoniflorin in perfusion liquid was established and the improved model of nasal perfusion in rats was used to screen out the species and amounts of absorption enhancer. In order to avoid the influence of the secretion and absorption of nasal cavity on the volume of perfusion fluid, the residual dose was calculated by using the volume correction method. Linear regression was carried out between the logarithm to the percentage of the residual dose and the corresponding time, and the slope of the regression line was exactly the absorption rate constant. Experimental results showed that hydroxypropyl-β-cyclodextrin and water-soluble azone can significantly improve the nasal absorption of paeoniflorin. Furthermore, water-soluble azone had the highest absorption rate constant and the best promoting penetration effect on intranasal administration preparations of paeoniflorin. It was also found that when the mass concentration of water-soluble azone in the perfusion liquid increased from 5 g•L⁻¹ to 20 g•L⁻¹, the absorption rate constant was gradually increased and peaked at 20 g•L⁻¹. When the mass concentration was increased to 30 g•L⁻¹, the absorption rate constant was decreased, indicating that the best mass concentration of water-soluble azone was 20 g•L⁻¹.
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Objective To compare the effects of chemical penetration enhancers and negative electret in promoting percutaneous penetrationof 5-fluorouracil (5-FU) through rat scar and dorsal skin in vitro, so as to lay a foundation for preparing delayed-release 5-FU electret transdermal patch. Methods The in vitro transdermal behaviors of 5-FU through rat scar and dorsal skin under the actions of 1 % azone, 10% ethyl oleate, —1 000 V electret, —1 500 V electret and —2 000 V electret were studied using improved Franze diffusion cell and high performance liquid chromatography (HPLC). Results (1) Both 1% azone and 10% ethyl oleate promoted the penetration of 5-FU through rat scar and dorsal skin, with the promoting effect of 10% ethyl oleate being better than that of 1% azone. (2) Although the transdermal behaviors of 5-FU were similar through scar skin and dorsal skin at the presence of chemical enhancers, the cumulative penetration amount through the scar skinwas less than that through the dorsal skin. (3) The negative electrets used in this study had satisfactory penetration promoting effect, with the promoting effect from strong to weak being —2 000 V electret > — 1 500 V electret > — 1 000 V electret Moreover, the scar skin also had less cumulative penetration amount of 5-FU than that of the dorsal skin under the action of electrets. Conclusion Both the chemical enhancers and electrets can enhance the transdermal delivery of 5-FU. 10% ethyl oleate and — 2 000 V electret have the best enhancing effect on 5-FU transdermal delivery and can be considered for preparation of 5-FU electret transdermal patch.
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Objective: To optimize the prescription of Compound Zhizi Gel (CZG) and to optimize the prescription technology of CZG. Methods: Orthogonal test, cold-resistant and heat-resistant tests were used to optimize the prescription technology. Using spreadability, glossiness, evenness, centrifugal stability, and in vitro transdermal diffusion as indexes, other excipients of prescription were optimized. Results: The optimal CZG prescription was Carbopol 940-glycerin-propylene glycol-triethanolamine-azone (1.5%:1.5%:3%:5%:5%). Conclusion: The optimized prescription is reliable and stable. It could meet the production requirements of CZG.
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OBJECTIVE: To synthesize bornyl salicylate and study its transdermal absorption in vitro. METHODS: Bornyl salicylate was prepared by esterification reaction of (+)-borneol and salicylic acid. The penetration of bornyl salicylate through mouse skin in vitro was measured using Franz diffusing cell with 2% azone as the penetration enhancer. The content of bornyl salicylate was determined by ultraviolet spectrophotometry. RESULTS: The structure of the target compound was identified by UV, IR and 1H-NMR. The transdermal absorption of bornyl salicylate was in accordance with Higuchi equation, in which cumulative dose of skin permeation (Q) has a linear relationship with the time. The average cumulative dose of skin permeation of bornyl salicylate for 12 h was 2.6112 mg, and the rate constant was 0.2539 mg m-2-1. CONCLUSION: The synthesis method of bornyl salicylate is simple. Bornyl salicylate can penetrate the skin of mice well with 2% azone as the penetration enhancer.
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Objective To study the effects of positive polarity electret combined with different concentrations of azone in promoting the transdermal delivery of cyclosporin A, so as to explore the feasibility and the rule of electret combined with chemical enhancers in promoting transdermal delivery. Methods Cyclosporin A was used as the model drug in the present study. Positive polarity electret was prepared using corona charge technique. Franz diffusion cell system and HPLC techniques were applied to investigate the roles of positive polar electret, azone of different concentrations and their combination in promoting penetration of cyclosporin A in vitro. Results Satisfactory penetration promoting effects for cyclosporin A was observed in excised skin 24 h after exposure to +500 V, +1 000 V and +2 000 V electret. Compared to the control group, 1%, 3%, and 5% azone promoted the steady-state penetration rates of cyclosporin A by 6. 72, 2. 11, and 1. 43 folds after 24 h exposure. Combination of +1 000V electret plus 1% azone showed better penetration promoting effect than other combinations, but electret with different positive charges and different concentrations of azone showed no synergistic effect in promoting cyclosporin A penetration. Conclusion Positive polarity electret has a penetration promoting effect for transdermal delivery of cyclosporin A. Positive polarity electret and azone show no synergistic effect on promoting penetration of cyclosporin A.
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Background Many researches confirmed that basic fibroblast growth factor (bFGF)plays an important role on the proliferation and differentiation of retinal progenitor cells,but its low intraocular permeability limits its clinical application.To explore an effective approach to enhance the intraocular permeability of bFGF has an important significance for the treatment of retinopathy. Objective This study was to investigate the effect of azone on bFGF intraocular permeability after its topical administration. Methods Eighteen New Zealand white rabbits were randomly divided into four groups on random number table method.Distilled water( blank control group),5％ bFGF eyedrops(5％ bFGF group ),0.4％ azone+5％ bFGF eyedrops (0.4％ azone + 5％ bFGF group ) and 0.4％ azone+ 10％ bFGF eyedrops (0.4％ azone + 10％ bFGF group)were topically administered in different groups at 5- minute interval for 3 times.Aqueous and vitreous fluid were extracted 30 minutes after administration of eyedrops,and those in the 0.4％ azone + 5％ bFGF group were obtained 30,60 and 120 minutes after administration.bFGF concentration in the aqueous and vitreous fluid was quantified with ELISA. Results The bFGF levels(A value)in aqueous and vitreous fluid were 0.1007±0.0100 and 0.1340±0.0100 after topical administration of the 5％ bFGF eyedrops,those in blank control group were 0.1363 ±0.0100 and 0.1130±0.0100,respectively,and those in the 0.4％ azone+5％ bFGF group and 0.4％ azone+10％ bFGF group were significantly higher than the 5％ bFGF group ( both P=0.000).However,no significant difference was found in bFGF levels between 0.4％ azone+5％ bFGF group and 0.4％ azone + 10％ bFGF groups in both aqueous and vitreous fluid ( P =0.985,0.098 ).A value of bFGF in aqueous was gradually increased with prolong of time in the 0.4％ azone+5％ bFGF group,with the values 0.9413±0.0300 at 30 minutes,0.3865±0.0300 at 60 minutes,and 0.2550±0.0300 at 120 minutes,showing a positive linear correlation between bFGF level and time( R2 =0.736,P =0.003 ),but no significant correlation was seen in vitreous sample(R2=0.196,P=0.233). Conclusions Azone can improve the intraocular penetration of bFGF eyedrops.Increasing the concentration of bFGF in eyedrop from 5％ to 10％ dose not change its intraocular distribution.The highest content of the bFGF in aqueous is at 30 minutes following the administration of 0.4％ azone+5％ bFGF eyedrops.
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Objective: To study the promoting effects of microneedle arrays on transdermal delivery of arbutin by comparing with the effect of chemical penetration enhancer azone. Methods: The microneedles were fabricated with single-crystal Si as starting material using a series of photolithography, thin-film deposition, and reactive ion etching techniques. Franz-cells were used in the transdermal delivery experiment with human abdominal skin. The study was divided into the following 3 groups; the microneedle group (arbutin hydrogel without penetration enhancer, and the skin was treated with microneedle arrays) ; the control group (arbutin hydrogels containing 1% , 3% , and 5% azone (W/V) , and the skin received no microneedle treatment); and blank control group (arbutin hydrogel without azone, and the skin received no microneedle treatment). Arbutin levels in the receptor solution, epidermis and dermis were determined by HPLC at 1, 3 , 6 , 12, 24, 36 and 48 h. The analyses were performed with a C18 column (250 mm X 4.6 mm, 5μm), at room temperature, mobile phase methanol : 1×10-3 mol/ml HCl solution (V/V, 5 : 95), flow rate 1 ml/min, and detective wavelength 282 nm. The accumulative penetration amount (Qr), steady-state flux (J s) and the accumulative deposition amount (Qs) were calculated. Results: The microneedles could pass the human skin. The standard curve was; C=0.000 2A=0.182 9 (r=0.999 9) , 0.4-50 μg/ml. The RSD values of intraday and interday precisions were 2.4% and 2.74%, respectively; and the recovery was higher than 90%. The values of Qr, Js, and Qs in the microneedle group were significantly higher than those in the 5% azone group (P<0.01). Conclusion: Microneedles can greatly promote the skin permeability and deposition of arbutin.
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Objective: To study the transdermal penetration absorption of Salviae Miltiorrhizae Radix et Rhizoma, the monarch drug in Xiaoyan Zhentong Cataplasm and to optimize the transdermal penetration enhancers of Xiaoyan Zhentong Cataplasm. Methods: The Franz diffusion cell was used to study the in vitro permeation behavior, and salvianolic acid B and Tanshinone IIA were chosen as indexes. Samples with different penetration enhancers were assayed by HPLC method to determine the cumulative permeation quantity and permeation rate of salvianolic acid B and Tanshinone IIA. Results: When azone - propylene glycol (1:1), the permeation rates of salvianolic acid B and Tanshinone IIA through rat skin in vitro were 3.62 and 1.35 μg/(cm2·;h), respectively, and the 24 h permeated amounts were 88.72 and 16.12 μg/cm2, respectively. Compared with the Xiaoyan Zhentong Cataplasm without penetration enhancers, the permeation rates increased by 6 and 10 times, respectively. Conclusion: The combination of Azone - propylene glycol (1:1) is an effective penetration enhancer both to water-soluble salvianolic acid B and liposoluble Tanshinone IIA.
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Objective: To study the enhancing effects of electret on transdermal delivery of lidocaine patches in vitro. Methods: In vitro rat skin permeation experiment was carried out with lidocaine patches, lidocaine paches with azone, positive/negative electret lidocaine patches, and positive/negative electret lidocaine patches with azone by using Franz diffusion cells. The accumulated lidocaine concentrations in rat skin treated with each kind of patches were examined by HPLC to investigate the influence of electret on transdermal delivery of lidocaine. Results: (1) The enhancement rates of 1%, 3% and 5% azone lidocaine patches 10 h after application were 1. 06, 1. 10 and 1. 66 folds (P<0. 05, 5% azone to lidocaine patch group) that of the lidocaine patch, respectively. (2) Lidocaine patches with negative electret containing 1%, 3% and 5% azone showed similar transdermal behavior to the corresponding chemical enhancer patches. (3) Lidocaine patches with positive electret containing 1%, 3% and 5% azone showed much better enhancing effect than the corresponding chemical enhancer lidocaine patches (P<0. 05). Besides, 5% azone together with positive electret showed a cooperative enhancing effect. Conclusion: Positive electret patch has better effect in enhancing transdermal delivery of lidocaine. Besides, the cooperative enhancing effect of azone with positive electret on transdermal delivery of lidocaine is in a concentration-dependent manner with azone.
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Objective To investigate the effect of two kinds of permeation enhancers,azone and clove bud oil,on transdermal permeation of Shuxiong cataplasm. Methods Cataplasm containing azone and clove bud oil,at different concentrations were prepared,with ferulic acid as the index,the role of enhancing permeation of azone and clove bud oil for the main active component were studied by in vitro permeation experiments. Results Both azone and clove bud oil at different concentrations could increase permeation. Clove bud oil was better than azone and the best concentration of Clove bud oil is 3%. Meanwhile,the permeation enhancing multiple of clove bud oil group was the highest which was 3.68. Conclusion With the cumulative permeation quantity of ferulic acid as the index,3% clove bud oil is more suitable to act as a permeation enhancer of Shuxiong cataplasm.
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0% Azone. Conclusion Azone can promote the transdermal absorption of the Matrine in Compound Kushen Gelatum. The effect of promoting penetration of 2% Azone is the best.
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OBJECTIVE:To evaluate the permeation enhancing effect of Flos Caryophylli volatile oil versus azone on diclofenac sodium.METHODS:Percutaneous absorption experiment was performed on the apparatus of isolated skin,and the penetrated amounts of diclofenac sodium at different time were measured,then the steady-state flux and enhancing rate were calculated,and the deposit effect of diclofenac sodium was investigated.RESULTS:Flos Caryophylli volatile oil and azone all had promotion effect on percutaneous absorption of diclofenac sodium,especially when they used in combination.Used either in combination or alone,they all had remarkable enhancement property on deposit effect of diclofenac sodium(P
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OBJECTIVE:To prepare Xiaocuo emulsion and to study its stability.METHODS:The formula and techniques were optimized with metronidazuo,cimetidine,chloramphenicol and salicylic acid as the chief ingredients,and with the uniformity of emulsion as the indicator.The stability test was performed using storage test and accelerated centrifugal test.RESULTS:The optimized formula was the following,5ml azone,4ml tween-80,1g metronidazole,2g cimetidine,2g chloramphenicol,1g salicylic acid and 100ml deionized water.CONCLUSION:The preparation is reasonable in formula,simple in preparative techniques,stable in quality and feasible in production.