Effect of radix scutellariae microemulsion gel on chronic eczema in mice model / 中国临床药理学与治疗学

AIM: To prepare radix scutellariae microemulsion gel and investigate its therapeutic effect on chronic eczema based on the previous research of radix scutellariae self microemulsion. METHODS: The gel matrix and humectant were optimized by single factor method and response surface method to obtain the formula and preparation technique of the gel. The Franz diffusion cell method was used to evaluate the transdermal properties of microemulsion and microemulsion gel in vitro. By establishing a chronic eczema model in the mouse ear, the swelling degree, swelling inhibition rate, pathological changes and tumor necrosis factor α (TNF-α), Interleukin-1β (IL-1β) and interleukin - 6 (IL-6) of radix scutellariae microemulsion gel were measured, to investigate the therapeutic effect on chronic eczema in mice. RESULTS: The physical and chemical properties of radix scutellariae microemulsion gel were stable. Compared with microemulsion, the microemulsion gel had better transdermal performance. The cumulative transdermal amount of baicalein and wogonin, the main components of microemulsion gel, was 1.85 times and 2.77 times of that of microemulsion respectively. Moreover, the steady flow rate and permeability coefficient of microemulsion gel significantly increased, and the lag time significantly shortened. Pharmacodynamic study showed that compared with the model group, the radix scutellariae microemulsion gel could significantly reduce the ear swelling of mice (P<0.05), and the serum inflammatory factor TNF - α, IL-1β and IL-6 reduced content by over 37%. Compared with the radix scutellaria aqueous extract and aqueous extract gel, the treatment of chronic eczema was better. CONCLUSION: The preparation process of radix scutellaria microemulsion gel is feasible, with strong transdermal property, and a significant therapeutic effect on chronic eczema.

Comparative study on in vivo and in vitro permeability of Huoxue Zhitong gel patch and microemulsion gel / 中国中药杂志

This study aims to establish a method for determination of paeonol(Pae), eugenol(Eug), and piperine(Pip) content in receptor liquid and research on the permeability and pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The Franz diffusion experiment was conducted to assess the percutaneous permeability, and the microdialysis method was employed to assess pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The content of Pae, Eug, and Pip in receptor liquid in vitro and in vivo was determined by HPLC and UPLC-MS. The Q_n and J_(ss) of Pae, Eug, and Pip in the gel patch were significantly higher than those in the microemulsion gel, indicating that the drug release was faster in the gel patch. The C_(max), AUC_(0-760), and MRT of Pae, Eug, and Pip in the gel patch were higher than those in the microemulsion gel, indicating that the gel patch can promote the penetration and prolong the skin residence of the drug. The results of this study provide reference for improving the dosage form of Huoxue Zhitong patch.

Preparation of compound liquorice microemulsion gel and its pharmacodynamics evaluation / 中国中药杂志

Based on the previous study of compound liquorice microemulsion, this paper aims to prepare the compound liquorice microemulsion gel and investigate its pharmacodynamics of chronic eczema. The type, dosage and adding method of gel matrix, and formula dosage of humectant were optimized by single factor method to obtain the formula and preparation technique of the gel. With glycyrrhizic acid, glycyrrhetin and oxymatrine used as evaluation indexes, the Franz diffusion cell method was adopted to monitor the in vitro release profile of the gel. Eczema model of delayed-type hypersensitivity in mice was chosen to detect the ear swelling rate, degree of inflammatory cell infiltration of ear pieces, and pathological changes of ear pieces, so as to investigate the therapeutic effect of the microemulsion gel. The preparation process of the compound liquorice microemulsion gel was stable. The release of glycyrrhizin and oxymatrine was most consistent with the Hixcon-Crowell kinetic model, while the release of glycyrrhizic acid was most consistent with the Ritger-Peppas kinetic model. The pharmacodynamics studies proved that compound liquorice microemulsion gel could significantly reduce the ear swelling rate in mice, with good anti-inflammatory effect as well as the ability to resist the pathological changes of chronic eczema and inhibit the infiltration of dermal inflammatory cells. Therefore, the preparation process of compound liquorice microemulsion gel is feasible, with stable drug release and a significant therapeutic effect on chronic eczema.

Effect and mechanism of essential oil from Zanthoxylum bungeanum in microemulsion gel preparation on percutaneous delivery of complex components / 中国中药杂志

This study aimed to investigate the transdermal enhancing effect of essential oil from Zanthoxylum bungeanum(Z. bungeanum oil) in microemulsion gel(ZO-ME-gel) on permeation of different components,and reveal the transdermal enhancing mechanism of ZO-ME-gel. A series of components with different log P values were selected as model drugs and encapsulated in ZO-ME-gel to simplify and characterize the complex components of traditional Chinese medicine. The transdermal behavior of the model drugs was further examined using the improved Franz diffusion cell method. Then attenuated total reflection Fourier transform infrared spectroscopy(ATR-FTIR),differential scanning calorimetry(DSC) studies and hematoxylin-eosin(HE) staining were used to investigate the effects of Z. bungeanum oil and ZO-ME-gel on keratin,intercellular lipids and microstructure of the stratum corneum(SC). The results showed that Z. bungeanum oil and ZO-ME-gel had a good transdermal enhancing effect on both hydrophilic and lipophilic drugs,and the best effect was achieved when log P value was-0. 5. The transdermal enhancing mechanism of Z. bungeanum oil and ZO-ME-gel was related to affecting the order of the SC lipids,changing lipid fluidity and protein conformation,and disrupting the integrity of the SC structure. 5% Z. bungeanum oil had greater transdermal enhancing effect and destruction of SC structure than ZO-ME-gel. These results suggested that Z. bungeanum oil loaded in microemulsion gel still had a good transdermal enhancing effect although the effect was not as great as Z. bungeanum oil itself,in addition,ZO-ME-gel was less irritating to the skin and safer to use,which had a guiding role in the development and clinical application of Z. bungeanum oil-containing traditional Chinese medicine topical preparations.

Formulation of in-situ ophthalmic microemulsion gel loaded with tacrolimus / 中国药学杂志

OBJECTIVE: To develop the formulation of in-situ ophthalmic microemulsion gel loaded with tacrolimus and evaluate its quality and safety. METHODS: The formulation to make tacrolimus microemulsion into thermosensitive in-situ ophthalmic gel was optimized by orthogonal experiment design using poloxamer 407(F127)and poloxamer 188(F68)as the thermosensitive gel matrix and the gelatinization temperature(Tg) of in-situ gel before and after diluting in simulated tear fluid as compounding effect indicator. The appearance, particle size, gelation temperature, morphological characteristics, rheological properties and dissolution behavior of the optimal in situ microemulsion gel were determined. Simultaneously, the residence time of tacrolimus microemulsion and its in-situ gel were examined using tacrolimus suspension eye drops as control. Irritation of these ophthalmic preparations after single and multiple dose administrations were evaluated against normal saline as control by intra-individual self-control method with Draize test criteria. RESULTS: The gel matrix of the optimal in-situ microemulsion gel containing 1 mg•mL-1 tacrolimus was composed of 140 mg•mL-1 F127 and 20 mg•mL-1 F68. The oval-shaped emulsion droplets homogenously dispersed in the in-situ emulsion gel with average particle size of 18.70 nm. Its gelation temperatures inside and outside eyes were 27.1 and 33.9 ℃, respectively. In vitro dissolution and release tests showed that its releasing characteristics followed zero-order kinetics. The average residence time of tacrolimus in-situ microemulsion gel in rabbit eyes was 22.67 min,significantly longer than those of the suspension and microemulsion of tacrolimus. No irritation was observed for tacrolimus suspension drops, microemulsion and its in-situ gel. CONCLUSION: It would be feasible to prepare tacrolimus temperature-sensitive in-situ gel from microemulsion with a simple preparation process. The gel was of controllable quality, good stability,good temperature sensitivity,and good spreadability, with low eye irritation. Compared with suspension eye drops, in-situ microemulsion gel can be expected to be a superior ophthalmic drug delivery system for hydrophobic drugs due to its steady and sustained release characteristics.

Pharmacokinetics of bullatine A in Aconitum brachypodum total alkaloids gel in transdermal delivery / 中国中药杂志

In this study, the changes of bullatine A in plasma and skin of mice with time in microemulsion gel and ordinary gel of Aconitum brachypodum total alkaloids were compared through UPLC-MS/MS, and their pharmacokinetic parameters were also compared and analyzed, to investigate the feasibility of microemulsion agent in the transdermal drug delivery. UPLC-MS/MS method for simultaneous determination of bullatine A in plasma and skin had high sensitivity and was in line with the pharmacokinetic study requirements for transdermal drug delivery. The main pharmacokinetic parameters for microemulsion gel in the plasma were as follows: Cmax=(37.62±14.31) μg•L⁻¹, Tmax=(3.40±1.34) h, AUC0-∞=(1 027.7±260) μg•L⁻¹•h⁻¹, MRT=(34.80±12.31) h, MRTlast=(10.68±0.57) h, t1/2=(23.11±9.20) h; main pharmacokinetic parameters for ordinary gel in the blood: Cmax=(52.23±15.90) μg•L⁻¹, Tmax=(4.00±0.00) h, AUC0-∞=(728.60±280.80) μg•L⁻¹•h⁻¹, MRT=(20.69±3.98) h, MRTlast=(9.34±0.42) h, t1/2=(14.69±3.15) h. The results showed that the microemulsion gel had more stable transdermal absorption, longer duration of action and higher bioavailability than ordinary gel, indicating that the microemulsion gel had a good and stable transdermal effect. There was no significant difference in bioavailability of bullatine A in skin between microemulsion gel and ordinary gel.

Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route

This study aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of Ibuprofen through intranasal route. Ibuprofen loaded mucoadhesive microemulsion (MMEI) was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (MEI) and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of ibuprofen via nasal route was studied by performing biodistribution study in Swiss albino rats. MEI was found to be transparent, stable and non ciliotoxic with 66.29 ± 4.15 nm, -20.9 ± 3.98 mV and 98.66 ± 1.01% as average globule size, zeta potential and drug content respectively. Transmission Electron Microscopy (TEM) study revealed the narrow globule size distribution of MEI. Following single intranasal administration of MMEI and MEI at a dose of 2.86 mg/kg, uptake of ibuprofen in the olfactory bulb was around 3.0 and 1.7 folds compared with intravenous injection of ibuprofen solution (IDS). The ratios of AUC in brain tissues to that in plasma obtained after nasal administration of MMEI were significantly higher than those after intravenous administration of IDS. Findings of the present investigation revealed that the developed mucoadhesive microemulsion gel could be a promising approach for brain targeting of ibuprofen through intranasal route.

O objetivo deste trabalho foi planejar microemulsão/mucoaesiva em gel a fim de melhorar a captação cerebral de ibuprofeno por via intranasal. A microemulsão para mucoadesão com ibuprofeno (MMEI) foi desenvolvida pela incorporação de policarbofil como polímero mucoadesivo em microemulsão otimizada (MEI) com base em Capmul (MCM) e foi submetida à caracterização, estabilidade, mucoadesão e naso-ciliotoxicidade. A captação cerebral de ibuprofeno pela via nasal foi estudada por meio de estudo de biodistribuição em ratos albinos suíços. MEI se mostrou transparente, estável e não ciliotóxica, com 66,29 ± 4,15 nm, -20,9 ± 3,98 mV e 98,66 ± 1,01%, respectivamente, de tamanho médio dos glóbulos, potencial zeta e conteúdo do fármaco. O estudo revelou o estreita distribuição do tamanho dos glóbulos de MEI. Após administração intranasal única de MMEI e MEI, em dose de 2,86 mg/kg, a captação de ibuprofeno no bulbo olfativo foi em torno de 3,0 e 1,7 vezes maior, comparativamente, à injeção endovenosa de ibuprofeno (IDS). As taxas de ASC em tecido cerebral em relação ao plasma, obtidas após administração da MMEI nasal, foram, significativamente, mais elevadas do que aquelas observadas após a administração intravenosa de IDS. Os resultados do presente estudo mostraram que a microemulsão/mucoadesiva em gel poderia ser uma abordagem promissora para o direcionamento cerebral de ibuprofeno por via intranasal.

Preparation and quality evaluation of tea tree oil microemulsion gel / 中草药

Objective: To study the prescription and preparation technology of tea tree oil (TTO) microemulsion gel. The quality and the stability were evaluated. Methods: The prescription and preparation technology were selected and optimized through the compatibility test and the pseudo-ternary phase diagram. TTO microemulsion gel was prepared by adding gelatin. The appearance, pH value, viscosity, moisture rate, and the drug concentration were evaluated. Results: The prescription composition of TTO microemulsion gel was TTO (0.6%), Cremophor RH-40 (1.2%), PEG 400 (0.2%), carbopol-980 (0.2%), glycerol (2%), with distilled water adding to 50 g. The optimum formulation exhibited clear and transparent, uniform exquisite, moderate viscosity, and well spreadable, with the particle diameter of (38.38 ± 2.30) nm, zeta potential of (-56.00 ± 5.82) mV, pH value of 5.52 ± 0.01, viscosity of (48 834 ± 5) Pa·s, moisture rate of (96.74 ± 0.52)%, and the drug-loaded of (5.79 ± 0.03) mg/g. The result of heat and cold resistance test showed that the preparation was needed to be stored at low-temperature. Conclusion: The preparation of TTO microemulsion gel is simple, corresponding to the main index of gelata for topical drug delivery preparation and offering the basis for further research and development.

Preparation of naproxen microemulsion-gel with high drug content and investigation of its in vitro transdermal delivery ability / 中国药学杂志

OBJECTIVE: To prepare naproxen microemulsion-gel with high drug content and adhesiveness, and investigate its in vitro transdermal delivery ability. METHODS: The ranges of microemulsion with the mixture of Tween 80 and Tween 20 as surfactant, carbitol as cosurfactant, peponida as oil, were defined through construction of the pseudo-ternary phase diagrams. Drug-loaded microemulsions were prepared by phase transfer temperature method. Naproxen microemulsion-gel was prepared by directly adding carbomer 980 into its microemulsion. The diffusion studies of all formulations were performed using a drug diffusion apparatus. The mean droplet sizes of naproxen microemulsion were measured via dynamic light scattering(DLS) on a Zetasizer, their microstructures were observed by transmission electron microscope(TEM). RESULTS: Microemulsion range was largest when the mass ratio of Tween 80 and Tween 20 was 3:1, surfactant and cosurfactant was 2:1. While the microemulsion composed of 5% peponida, 35% emulsifier and 60% water, drug loaded in microemulsion can attain 4%, which was accorded with the characterization of microemulsion. Adding 2.5% carbomer 980 into optimization microemulsion, even and transparence microemulsion-gel was obtained, which has the combination of o/w microstructure of microemulsion and the three-dimensional gel network of hydrogel. The viscosity of microemulsion-gel was increased from 104.5 mPa · s to 18.9 Pa · s, the steady-state permeation rates through excised cavia skin increased from(531.912±1.3) to(640.327±0.7) μg · cm-2 · h-1. CONCLUSION Naproxen microemulsion-gels prepared by selected carbitol as cosurfactant can obtain high drug content and percutaneous absorbtion, exhibit favourable adhesiveness, which may be a promising new dosage form for transdermal delivery of naproxen.