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Objective:To investigate the effect of the production process of Zushima Guanjie Zhitong Gao from solvent method to hot-pressed method on <italic>in vitro</italic> kinetic behavior of this preparation. Method:Solvent and hot-pressed methods were used to prepare three batches of samples above pilot scale， and <italic>in vitro</italic> release and percutaneous penetration of the index components （7，8-dihydroxycoumarin and methyl salicylate） in Zushima Guanjie Zhitong Gao were investigated by modified Franz diffusing cells. Result:The contents of 7，8-dihydroxycoumarin and methyl salicylate in Zushima Guanjie Zhitong Gao prepared by solvent method were 73.72， 494.67 μg/patch， and their contents in hot-pressed method samples were 159.21， 2 638.99 μg/patch， respectively. In the solvent method samples， the average cumulative release amounts of 7，8-dihydroxycoumarin and methyl salicylate in 24 h were 2.04， 12.21 μg， and their average cumulative release amounts in 24 h of hot-pressed method samples were 2.16， 36.24 μg， respectively. In the solvent method samples， the average cumulative permeation amounts of 7，8-dihydroxycoumarin and methyl salicylate in 24 h were 0.38， 2.79 μg， and they were 0.40， 7.49 μg in hot-pressed method samples. The cumulative release and permeation amounts in 24 h of 7，8-dihydroxycoumarin in the hot-pressed method samples were basically the same as those of the solvent method samples， but the cumulative release and permeation amounts in 24 h of methyl salicylate in the hot-pressed method samples were significantly higher than those of the solvent method samples （<italic>P</italic><0.05）. Conclusion:The retention of 7，8-dihydroxycoumarin and methyl salicylate by hot-pressed method is better than that of the solvent method. The process change has no significant effect on the <italic>in vitro</italic> kinetics of 7，8-dihydroxycoumarin in Zushima Guanjie Zhitong Gao， however， after the change from the solvent method to the hot-pressed method， the methyl salicylate in this preparation has a higher cumulative release and permeation amounts.
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Objective: To optimize the formulation of Jieyu Anshen Gel Plaster (JAGP) and evaluate its quality. Methods: With the bonding strength and sensory evaluation scores as indicators, the formulation of JAGP was optimized by using orthogonal experiment design method. Then the content of methyl eugenol, elemicin, β-asarone and α-asarone in JAGP were determined by GC-MS and the in vitro transdermal properties were studied by modified Franz diffusion cells. Results: The optimized blank matrix formulation was as following: NP700 of 3%, glycerol of 36%, PVP K30 of 4% and aluminium glycinate of 0.08%. The containing ointment of prepared gel plaster was 217.4 mg/cm2 and the effective component of the total index in gel paste was 5.77 mg/paste. Then the accumulated transdermal permeation of methyl eugenol, elemicin, β-asarone and α-asarone was (81.798 6 ± 14.872 6), (72.110 2 ± 17.776 1), (146.390 6 ± 33.794 1), (5.522 6 ± 1.279 6) μg/cm2, respectively within 24 h, which were all consistent with the zero-order equation. Conclusion: The preparation of JAGP with good stability and drug-releasing properties conformed to the relevant quality requirement, And this study provides certain basis for the development of production.
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Objective: To prepare capsaicin emulgel and investigate its transdermal delivery ability in vitro, analgesic effect and skin irritation. Methods: The effect of different penetration enhancers on the percutaneous permeation of emulgel in vitro was investigated by using the modified Franz diffusion cell. The optimal prescription was determined and the transdermal absorption of capsaicin emulgel was investigated; Analgesic effect was tested by hot plate method; The rabbit skin irritation test was used to evaluate the safety of capsaicin emulgel. Results: Peppermint oil, eucalyptus oil, and azone three kinds of penetration enhancers had no significant effect on enhancing permeation effect, so the final formulation of the emulgel was optimized without penetration enhancers. In vitro transdermal test showed that the cumulative permeation quantity of commercially available creams, self-made gels and emulgel was 18.98%, 37.04%, and 54.75%, respectively. In the hot plate method, the inhibitory rates of commercially available creams and high dose of emulgel after oral administration of 30, 60, and 90 min were 14.07%, 14.49%, 16.81%, 18.63%, 22.50%, and 25.57%. The skin irritation test results indicated that emulgel has no irritation to the rabbit skin. Conclusion: Capsaicin emulgel has good percutaneous permeability without skin irritation, the middle and high dose of emulgel have good analgesic activity, which will supply evidence for the selection for the local transdermal formulations of capsaicin.
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objective To optimize the preparation technology of sulfuric in situ gel and study the infiltration experiment of different dosage forms. Methods Shufei in situ gel was prepared by cold cut method with poloxamer 188 (P188) and poloxamer 407 (P407) as gel base. Using gelling temperature index, the dosage range of gel matrix P407 and P188 in Shufei in situ gel was determinated by the single factor and star design-response surface methods to get the best prescription of Shufei in situ gel. The transdermal diffusion process of Shufei in situ gel was carried out in Franz diffusion cells to explore the permeation mechanism. Results The optimized prescription of Shufei in situ gel was as follow: The ratio of gel matrix to drug at 1:3, P188 dosage of 4%, P407 dosage of 22.5%, and the phase transition temperature within 32-36 ℃ to form gel. The releases of sinapine thiocyanate and genkwanin in Shufei in situ gel were all in line with the Higuchi release model. Conclusion The preparation process of Shufei in situ gel is stable and feasible with reliable product quality and good application prospect, which is suitable for industrial production and clinical application.
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AIM To compare the percutaneous penetration performance of three paeonol gels.METHODS Franz diffusion cell method was applied to investigating the penetration and retention behaviors of eutectic mixturebased nanoemulsion,ordinary nanoemulsion and saturated solution gels onto mouse skins in vitro.The retention and permeation amounts in stratum corneum and hair follicles of volunteers smeared with gels were compared by tape stripping method.RESULTS The accumulative permeation and retention amounts of various gels onto mouse skins in vitro were in sequence of eutectic mixture-based nanoemulsion gel ＞ ordinary nanoemulsion gel ＞ saturated solution gel.The main retention of all the three gels was observed on the volunteers' skin surface,and the permeation amounts of eutectic mixture-based nanoemulsion,ordinary nanoemulsion gels,and their accumulative permeation amounts in stratum corneum and hair follicles were significantly higher than those of saturated solution gel (P ＜0.05).CONCLUSION Nanoemulsion technology can significantly promote the percutaneous penetration performance of paeonol.
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OBJECTIVE:To study the dermal pharmacokinetic difference of triptolide in normal and diabetic rats,and to pro-vide reference for rational drug use in the clinic. METHODS:12 Wistar rats were randomly divided into normal group and diabetic model group(0.1%streptozotocin intraperitoneally),with 6 rats in each group. Both group were given Triptolide cream 0.5 g to ab-dominal skin,and dialysate was collected by microdialysis every 30 min for consecutive 12 h. Subcutaneous concentration was de-tected by HPLC-MS,and subcutaneous concentration-time curves were analyzed and compared between two groups,and Winnon-lin 5.0.1 software was used to calculate pharmacokinetic parameters. RESULTS:The pharmacokinetic parameters of normal group and diabetic model group were that cmax were(1.54±0.37)and(5.12±1.34)μg/ml;tmax were(7.32±0.24)and(6.21±0.35)h;AUC0-12 h were (12.65 ± 4.64) and (37.43 ± 5.23)μg·h/ml,with statistical significance (P<0.05). CONCLUSIONS:The change of dermal structure caused by diabetes can increase percutaneous penetration amount of triptolide in rats,and drug dosage should be reduced according to circumstances so as to reduce side effects.
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Objective: To comprehensively evaluate the in vitro percutaneous penetration and provide the experimental basis of in vitro kinetics for new drug development of Jinhuang Gel. Methods: The skin penetration of Jinhuang Gel was investigated through in vitro excised rat skin using the improved Franz diffusion cell. HPLC fingerprint of receptive solution and skin retention was established and analyzed using principal component analysis (PCA). The common peaks of HPLC fingerprint between Jinhuang Gel and Jinhuang Ointment were selected and each area was calculated to obtain the PCA biplot. Paeoniflorin as a representative of common peaks was used to investigate the in vitro permeation kinetics. Results: The results showed that the PCA biplot based on common peaks areas displayed that the global in vitro transdermal absorption effects of Jinhuang Gel were significantly better than those of Jinhuang Ointment. The in vitro transdermal absorption of paeoniflorin followed zero kinetics, and the cumulative permeation amount, permeation rate, and skin retention of paeoniflorin from Jinhuang Gel were superior to those from Jinhuang Ointment. Conclusion: Jinhuang Gel could improve the overall effects of in vitro percutaneous absorption. PCA is an effective means for investigating in vitro percutaneous absorption experiments of Chinese materia medica for transdermal administration.
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Objective To prepare hot‐melt pressure sensitive adhesive (HMPSA) transdermal patches of progesterone and investigate the release characterization in vitro .Methods SIS HMPSA was used as matrix material ,modified Franz diffu‐sion cell and excised female rat skin were used as model ,the concentration of progesterone was determined by HPLC .The thickness of patch and penetration enhancers was screened out by permeation rate .Results 2% IPM was used to prepare pro‐gesterone HMPSA transdermal patch ,thickness was 300 μm ,the cumulative permeation curve was Q=6 .172 1 t-5 .457 7 (r=0 .998 8) .The cumulative releases of the patches in 24 h was 144 .17 μg/cm2 . The permeation rate was (6 .17 ± 0 .49)μg/(cm2 · h) .Conclusion The progesterone HMPSA transdermal patch had good transdermal release in vitro ,which would have good clinical application prospect .
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Objective To explore the release and percutaneous penetration of cyclovirobuxine D patches at different concentrations in vitro. Methods The release curves of cyclovirobuxine D patch in vitro were fitted by ritger-peppas mathematical model, and the patch release mechanism was discussed according to the fitting parameters. At the same time, compared the percutaneous permeability characteristics of 0.25,0.5,1.0,2.0 mg.( cm2 )-1 of cyclovirobuxine D patch by using a modified Franz diffusion cell, with isolated rat skin serving as transdermal barrier. Results Ritger-Peppas model fitting equation for cyclovirobuxine D patch [1.00 mg.(cm2)-1]was: Mt/M=0.964 6 t1.621 6.And the percutaneous penetration curve was best fitted to Higuchi kinetics equation.The drug release rate from the patch matrix was greater than the rate of penetration through the skin, indicating the patch at the time through rat′s skin was a passive diffusion process, and transdermal process was rate-limited by skin. Conclusion Kinetics equation fitting is an effective method for analyzing drug release and permeation behavior of cyclovirobuxine D patch in vitro.
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OBJECTIVE: To prepare mangiferin transfersomes and investigate its transdermal delivery characteristics. METHODS: Mangiferin transfersomes were prepared by the method of film-dispersion, the in vitro percutaneous penetration study was conducted in the modified Franz diffusion cell, the distribution of transfersomes in skin was investigated by fluorescent tracer method, and the rat back airbag inflammation model was used to preliminarily evaluate the anti-inflammatory effect of mangiferin transfersomes with prostaglandin E2 (PGE2) content as the indicator. RESULTS: The average particle size of mangiferin transfersomes was (84.50 ± 5.26)nm, the polydispersity index (PDI) was (0.21 ± 0.012), the Zeta potential was(-10.83 ± 0.66)mV, the encapsulation efficiency (EE) was (64.07 ± 2.10)%, and the deformability was (20.00 ± 0.30)%; the cumulative permeation quantities in 24 h and intradermal retention of mangiferin transfersomes were (313.67 ± 22.62) and (60.34 ± 8.10) μg · cm-1, respectively. Fluorescent tracer method showed that the fluorescence intensity of FITC transfersomes in the inside of skin was stronger than that of FITC solution at 8 h. Anti-inflammatory test showed that the PGE2 contents in the middle and high dose mangiferin transfersomes groups decreased significantly. The anti-inflammatory effect of the high dose mangiferin transfersomes was even close to that of compound dexamethasone cream. CONCLUSION: Transfersomes can promote the percutaneous penetration of mangiferin, increase its intradermal retention, and enhance the anti-inflammatory effect of mangiferin significantly.
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Objective To prepare celastrol ethosomes and to observe the permeability characteristics of the ethosomes which act as the transdermal delivery carriers of celastrol in vitro. Methods Celastrol ethosomes were prepared by ethanol injection method, and then the encapsulation efficiency, particle size, polydispersity index ( PDI) and zeta potential of the ethosomes were analyzed. TP2A intelligent percutaneous penetration instrument was used to compare the skin penetration properties of celastrol ethosomes, celastrol solution and the mixture of blank ethosomes with celastrol solution. Results The prepared celastrol ethosomes were spherical, and the average particle size was (401.3 ± 5.5) nm, PDI was 0.21± 0.02, steady zeta potential was (-2.75 ± 0.1) mV, and average encapsulation efficiency was ( 80.6 ± 0.7) %. The amount of accumulative penetration of celastrol ethosomes at 48 h was 76.86 μg·cm -2 and the permeation rate was 1.640 9 μg·cm -2·h -1, which were significantly higher than the celastrol solution and the mixture of blank ethosomes with celastrol solution. Conclusion The prepared ethosomes have high encapsulation efficiency, uniform particle size and stable quality, and are beneficial to the transdermal absorption of celastrol.
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Objective To compare transdermal penetration of triamcinolone acetonide liposparticles (TAA-LPPs) and TAA-Ethosomes in vitro. Methods The TAA-LPPs and TAA-Ethosomes were produced and the morphology was observed by transmission electron microscope,particle size was detected by laser particle analyzer. The percutaneous permeability in vitro was tested by modified Franz diffusion pools. The amount of penetrated triamcinolone acetonide and the retention in the skin were de-termined by HPLC. Results The shape of TAA-LPPs and TAA-Ethosomes was almost spherical with mean diameter of (99. 9±1. 3) and (105±1. 4) nm, respectively. The cumulative transdermal penetration of TAA-LPPs, TAA-Ethosomess and TAA suspension was (53. 59±4. 40),(87. 03±4. 87),and (30. 54±8. 61) μg·(cm2 ) -1 , respectively . The drug retention in the skin after 32 h was (1. 02±0. 13), (0. 62±0. 08), (0. 55±0. 17) μg·(cm2 ) -1 , respectively. Conclusion TAA-LPPs is better for transdermal administration of triamcinolone acetonide by reducing systemic absorption of the drug.
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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.
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Objective To investigate the penetrative ability of amlodipine gels and to evaluate their effect on the survival of rat dorsal ischemic random skin flaps.Methods 0.5 ％,1.0 ％,1.5 ％,2.0 ％,and 2.5 ％ amlodipine gels were made.The accumulative penetrative quantities of amlodipine through rat skin were assayed with a modified Franz's diffusion cell in vitro.Pure gel without amlodipine,0.5 ％ and 1.5 ％ amlodipine gel were respectively applied on rat random ischemic skin flap once a day for 7 days.The viable area was measured on the seventh postoperative day and the quantities of amlodipine within skin flap were also detected at 2 and 6 hours after application of amlodipine gel.Results The accumulative penetrative quantities of amlodipine increased in time-and concentration-dependent manner (P＜0.05).Accumulative quantities of 0.5 ％ and 1.0 ％ amlodipine gel were lower than those of 1.5 ％,2.0 ％,and 2.5％ gel,respectively (P＜0.05).The quantities of amlodipine within flap tissue in 1.5 ％ amlodipine gel was higher than that of 0.5 ％ amlodipine gel (P＜0.05).The survival area of flap in 0.5 ％ amlodipine gel group (391.4±65.4) mm2 was higher than those of the pure percutaneous gel group (192.9±56.8) mm2 and the control group (191.0±50.2) mm2(P＜0.05),but no significant difference was seen between 1.5 ％ amlodipine gel group (265.7+88.3) mm2 and control group (P＞0.05).Conclusions Amlodipine could penetrate into skin tissues.0.5 ％ amlodipine gel could significantly increase survival area of ischemic random skin flap.
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OBJECTIVE: To study the physical and chemical properties and transdermal delivery characteristics oi capsaicin. METHODS: Equilibrium solubility method, ultraviolet spectrophotometry, bottle-shaking method, differential scanning ealorimetry (DSC) and in vitro diffusion cell method were used to determine the apparent solubility, dissociation constant, apparent oil/water partition coefficient, melting point and percutaneous penetration of capsaicin, respectively. And the permeation characteristics were evaluated by lag time method. RESULTS: Capsaicin was slightly dissolved in water, and the apparent solubility was (22.85 ± 0.06) mg · L-1. It was a weak base with a dissociation constant of (10.25 ± 0.11). The apparent oil/water partition coefficient of capsaicin changed with the pH value, and increased when pH was greater than 8. Its melting point was 60.20°C. The residence time(ttag) was (2.437 ± 0.273) h, the permeability coefficient (P) (7.012 ± 0.341) × 10-2cm · h-1, and the percutaneous penetration rate (Js) (4.647 ± 0.226) μg · cm-2 · h-1. CONCLUSION: Capsaicin possesses appropriate physical and chemical properties for percutaneous penetration and exhibits excellent percutaneous penetration.
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Objective To study the effect of phonophoresis on transdermal delivery of sinomenine hydrochloride ( SH ) gel in vitro. Methods Ultrasound at one of two frequencies ( 800 kHz or 1 MHz) was applied with a sonicator with a transducer in this study. The skin of male Sprague-Dawley rats was used as the model and SH gel was used as the ultrasound couplant. The permeation rate of SH was detected using a modified Franz diffusion cell maintained at 32±0.5℃ and filled with 20% polyethylene glycol 400 physiological saline solution. The transdermal phonophoresis experiments were carried out in five groups: Group Ta, f=800 kHz, / = 0.75 W/cm2, t = 10 min:Group Tb,f=1 MHz,I=0.7 W/cm2, t=10 min; Group Tc,f=1 MHz,I=0.35 W/cm2, t=10 min; Group Td,f=800 kHz, I = 1.5 W/cm2, t = 10 min and Group Tc,f=800 kHz, I=1.5 W/cm2,t=5 min. There was also a control group (C) in which the SH was allowed to diffused passively. Samples were withdrawn at the indicated intervals and the concentration of SH was determined by high-performance liquid chromatography. The transdermal parameters such as average accumulated delivery quantity per unit area Q8h, average transdermal steady delivery rate J, and Tlag were calculated. Results The Q8h and Js of the control group were 20.65±10.23 μ/cm2 and 3.02±0.11μ/cm2/h respectively. The phonophoresis parameters in groups Ta and Tb were, on average, significantly higher than in the control group. The parameters in group Tb were significantly larger, on average, than in Te. In group Td the parameters were significantly larger than in groups Ta and Te. Conclusions The results show that phonophoresis can enhance the transdermal delivery of SH. Phonophoresis variables such as frequency and time influence its effects on drug permeation. Almost no change was observed in the structure of the skin after phonophoresis, though under a scanning electron microscope the surface of the corneum appeared rough and porous. Phonophoresis is there-fore an effective and safe method for SH transdermal delivery, and the effect is positively relation with the applied intensity and exposure time.
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Os procedimentos cirúrgicos e cosmiátricos realizados pelos dermatologistas, tais como laser para epilação, remoção de tatuagem e rejuvenescimento, curetagem, eletrocoagulação, crioterapia, preenchimentos injetáveis, aplicação de toxina botulínica, escleroterapia, "peelings" químicos, entre outros, requerem muitas vezes o uso de anestésicos locais para o conforto do paciente. Tradicionalmente, o agente anestésico de escolha é a lidocaína injetável. Embora seja muito eficaz na produção de anestesia local total, a injeção causa dor. Há vários anestésicos tópicos disponíveis que podem aliviar o desconforto causado por esses procedimentos, sem a necessidade de injeções.
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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 observe the effects of borneol affecting the transdermal amount of drugs.METHODS:Drugs permeation tests were performed in a two-compartment diffusion cell through cobra skin in vitro,in rabbits and on the human skin blanching assay in vivo,respetively.RESULTS:In vitro,borneol increased the percutaneous transport of metronidazole and 5-fluorouracil.The potency of 3.0% borneol was different from that of 1.0%borneol.On the human skin beanching assay in vivo it indicated that borneol enhanced the bioavailability of percutaneous penetration of triamcinolone acetonide acetate.In rabbits,borneol increased AUCo～12h of salicylic acid in plasma.CONCLUSION:It indicated borneol is a effective percutaneous penetration enhancer.
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AIM: To compare the release and percutaneous penetration in vitro among 2 kinds of the psoralen ointments and its gel. METHODS: Dissolution tester and Franz diffusion cells were adopted as the release and percutaneous penetration in vitro, and HPLC was used to measure the amount of psoralen in the releasing solution, receiving solution and the skin. RESULTS: The release and percutaneous penetration of psoralen from the 3 kinds of preparation conformed to the zero kinetic equation. The steady-state penetration rate of psoralen in the gel was higher than that of the ointment, and there was no significant difference between 2 kinds of ointments. CONCLUSION: Gel is a better choice for percutaneous penetration of psoralen.