In Vitro Pharmacokinetics and Pharmacodynamic Evaluation of Jiaojiang Cataplasms / 中国实验方剂学杂志

ObjectiveTo study the in vitro kinetics of Jiaojiang cataplasms and evaluate its pharmacodynamics， so as to provide a feasible basis for the development of this preparation. MethodThe improved Franz diffusion cell was used for the in vitro release in semipermeable membrane and transdermal absorption in in vitro mouse skins. The contents of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb1 were determined by high performance liquid chromatography （HPLC）， to evaluate the in vitro release and transdermal absorption of Jiaojiang cataplasms. The mobile phase of 6-gingerol and hydroxy-α-sanshool was water-acetonitrile-methanol （2∶1∶1） with the detection wavelength of 280 nm. The mobile phase of ginsenoside Rb1 was acetonitrile-0.1% phosphoric acid aqueous solution （31∶69） with the detection wavelength of 203 nm. A mouse intestinal paralysis model was established， and mice were randomly divided into five groups， namely sham operation group， model group， domperidone group （3.9 mg·kg-1） and high- and low-dose groups of Jiaojiang cataplasms （6.2， 3.1 g·kg-1， measured by crude drug dosage）， to observe the effect of this preparation on gastrointestinal propulsion function. ResultAverage release rates of hydroxy-α-sanshool， 6-gingerol and ginsenoside Rb1 at 24 h were 16.41， 4.23， 4.15 μg∙cm-2∙h-1， the average transdermal rates of them at 24 h were 2.31， 0.64， 0.29 μg∙cm-2∙h-1， their skin retention values were 19.56， 3.59， 1.61 μg， respectively. According to the Ritger-Peppas equation， the release of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb1 was non-Fick diffusion. The high-dose group of Jiaojiang cataplasms could improve intestinal function of model mice after small intestinal friction injury， and promote intestinal peristalsis and small intestinal propulsion rate （P<0.05）. ConclusionJiaojiang cataplasms has in vitro release and transdermal properties， the in vitro release conforms to Higuchi equation， and transdermal absorption behavior conforms to zero-order kinetic equation， which can improve the postoperative function of the small intestine and the propulsion function of small intestine. It preliminarily indicates that the preparation has certain clinical development value.

Effects of hyaluronic acid with different molecular weight on the transdermal absorption of reduced glutathione / 中国药科大学学报

@#This paper aimed at studying the effects of hyaluronic acid (HA) with different molecular weights on the transdermal absorption and retention of reduced glutathione (GSH) in the isolated skin of SD rats. Franz diffusion cell method was used to investigate the effects with different molecular weights HA on the in vitro transdermal penetration of GSH and the storage in different layers of the skin. AutoDock molecular docking was used to study the interaction between GSH and HA. Attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR) and H&E section staining were used to characterize the changes and effects of lipids and proteins in the rat stratum corneum after HA acts on the skin. The results of in vitro transdermal experiments showed that HA with different molecular weights had a significant impact on the amount of GSH passing through the skin, that as the molecular weight of HA increased, the effect of preventing GSH from passing through the skin became stronger, that in terms of skin storage, HA with different molecular weights could increase the storage of GSH in the stratum corneum, and that HA with a molecular weight below 7K could also significantly increase the storage of GSH in the dermis. The molecular docking results showed that HA and GSH had a relatively strong interaction, which could form intermolecular hydrogen bonds; and the results of ATR-FTIR and H&E staining showed that HA could interact with lipids and keratins in the stratum corneum of the skin. Such interaction can increase the permeability of the stratum corneum of the drug, however, as a water-soluble GSH, it may be involved in the formation of intermolecular hydrogen bonds with HA. In the structure of HA hydrogel, the amount of GSH drug passing through the intact skin is reduced; but at the same time, this interaction also provides a reservoir for the formation of GSH, thus increasing its storage in the skin. Through comparison of the storage capacity of GSH in the stratum corneum and dermis of the isolated skin due to the increase of HA with different molecular weights, it has been found that the storage capacity of HA with low relative molecular weight is the best.

Effects of Different Penetration Enhancers on in vitro Transdermal Permeation of Flavaspidic Acid BB Cream / 中国药房

OBJECTIVE：To study the effects of different penetration enhancers on in vitro transdermal permeation of Flavaspidic acid BB cream. METHODS ：Flavaspidic acid BB cream was prepared ，containing 11 kinds of different penetration enhancers as 1％ azone，2％ azone，3％ azone，4％ azone，1％ menthol，1％ propylene glycol ，1％ oleic acid ，1％ azone+1％ menthol，1％ azone+1％ propanediol，1％ azone+1％ oleic acid or 1％ menthol+1％ propanediol. Modified Franz diffusion cell was adopted using abdominal skin of isolated male rat as transdermal barrier. The content of flavaspidic acid BB was determined by UPLC. The accumulative transdermal amount （Q24 h）and percutaneous permeability （Jss）within 24 h were calculated ；and compared with Flavaspidic acid BB cream without transdermal enhancer ，the enhancement ratio （ER）was calculated. RESULTS ： Q24 h of Flavaspidic acid BB cream with above 11 kinds of transdermal enhancers were （82.96±7.15），（80.17±0.66），（78.22± 1.87），（73.53±1.24），（35.65±2.23），（34.02±1.73），（42.68±2.66），（33.94±1.37），（34.16±1.54），（46.78±1.21），（43.66±1.69） μg/cm2，respectively. Jss value were （5.26±0.10），（4.69±0.12），（4.45±0.45），（4.00±0.06），（3.74±0.33），（3.23±0.18）， （3.73±0.53），（3.14±0.47），（3.54±0.11），（3.98±0.34），（4.34±0.14）μg（/ cm2·h），respectively. ER were 2.055，1.831，1.738， 1.564，1.462，1.263，1.456，1.227，1.385，1.557，1.698，respectively. CONCLUSIONS ：All of the above transdermal absorption enhancers can enhance the percutaneous absorption of Flavaspidic acid BB cream ，among which ，1％ azone is the best.

Preparation of Self-emulsifying Preparations of Chinese Medicinal Ingredients Based on Identical Carrier System and Investigation of Their Transdermal Absorption Characteristics in Vitro / 中国实验方剂学杂志

Objective:To prepare self-emulsifying carrier system which was suitable for three Chinese medicinal ingredients(baicalein,berberine and allicin),and investigate transdermal absorption effect in vitro of these three self-emulsifying preparations. Method:The optimum formulation and dosage were screened by the saturated solubility method,pseudo-ternary phase diagram method and orthogonal experiment.Transdermal absorption test in vitro was carried out with excised rats skin and Franz diffusion cell.The cumulative penetration amounts of baicalein,berberine and allicin in the identical self-emulsifying system were determined by HPLC and compared with baicalein powder,berberine powder and allicin powder,respectively. Result:The optimum formulation was ethyl oleate-cremophor RH40-polyethylene glycol(PEG)400.The self-emulsifying preparation had a suitable particle size with a relatively regular spherical shape.At 10 h of transdermal absorption,the transdermal rates of baicalein,berberine and allicin in identical self-emulsifying system were 6.898 6,7.600 4,190.040 μg·cm-2·h-1,the cumulative penetration amounts of them were 71.38,85.54,1 795.16 μg·cm-2,respectively. Conclusion:The self-emulsifying carrier system is prepared successfully,which can be used by different kinds of Chinese medicinal ingredients,and the transdermal absorption effect in vitro of these self-emulsifying preparations is good,which can provide experimental basis for the preparation and transdermal absorption of self-emulsifying preparation of Chinese herbal compound.

Preparation and evaluation of four kinds of mixed essential oil liposomes in Jieyu Anshen Formula / 中国中药杂志

In order to increase the stability and solubility of essential oil in Jieyu Anshen Formula, this study was to prepare the essential oil into liposomes. In this experiment, the method for the determination of encapsulation efficiency of liposomes was established by ultraviolet spectrophotometer and dextran gel column. The encapsulation efficiency and particle size of liposomes were used as evaluation indexes for single factor investigation and Box-Behnken design-response surface method was used to optimize the design. Then the optimal formulation of volatile oil liposome was characterized using methyleugenol, elemin, β-asarone and α-asarone as index components. Finally, the in vitro transdermal properties of liposomes were studied by modified Franz diffusion cell. The results showed that the concentration of lecithin, the mass ratio of lecithin to volatile oil, and the stirring speed were the three most significant factors affecting the liposome preparation. The optimum formulation of volatile oil liposome was as follows: the concentration of lecithin was 7 g·L~(-1); mass ratio of lecithin to volatile oil was 5∶1; and the stirring speed was 330 r·min~(-1). Under such conditions, the prepared liposomes had blue emulsion light, good fluidity, half translucent, with particle size of(102.6±0.35) nm, Zeta potential of(-17.8±0.306) mV, permeability of(1.67±1.01)%, and stable property if liposome was stored at 4 ℃. 24 h after percutaneous administration, the cumulative osmotic capacity per unit time was(30.485 2±1.238 9),(34.794 8±0.928 3),(26.677 1±1.171 7),(3.066 2±0.175 3) μg·cm~(-2)respectively for methyleugenol, elemin, β-asarone and α-asarone. In vitro transdermal behaviors of methyleugenol, elemin, β-asarone and α-asarone in liposomes were all consistent with Higuchi equation. The prepared volatile oil liposomes met the relevant quality requirements, providing a reference for further research on preparation of multi-component Chinese medicine essential oil liposomes.

Effects of natural borneol and synthetic borneol on the transdermal absorption of emodin / 中国药学杂志

OBJECTIVE: To investigate the effect of natural and synthetic borneol on the transdermal absorption of emodin. METHODS: The supplying and receiving solutions containing emodin were selected from the abdominal skin of mice in vitro, and the samples were analyzed by HPLC. The cumulative permeability, permeability rate and permeability enhancement factor were used as the evaluation indexes of the permeability enhancement effect. RESULTS: The saline containing 1% Tween 80-80% ethanol and 60% ethanol could increase the solubility of emodin to 648 μg•mL -1 and obtain conditions of leaking trough. The penetration rate of emodin was 648 μg•mL - 1 > 569 μg•mL -1 > 457 μg•mL -1 in the range of concentration. The penetration enhancement effect of synthetic borneol was 2% > 4% > 1% > blank control group > 3% and 5%, and the steady-state permeation rates of 2% natural borneol (15.90 μg•cm- 2•h - 1 ) were higher than those of 2% synthetic borneol(12.44 μg•cm-2•h-1). CONCLUSION: Natural borneol and synthetic borneol can promote the transdermal penetration of emodin, which is limited by their concentration. This provides an experimental basis for the selection of emodin transdermal enhancers.

Preparation of dl-tetrahydropalmatine ethosomes and their ex vivo transdermal permeation properties / 中草药

Objective To prepare dl-tetrahydropalmatine (dl-THP) ethosomes (ETS) and elucidate their transdermal absorption properties. Methods Dl-tetrahydropalmatine ethosomes (dl-THP ETS) were prepared by ethanol injection combined with pH-gradient active drug-loading method. Their physicochemical properties including elasticity, vesicle size, morphology and entrapment efficiency were characterized. Franz diffusion cells were used to investigate the ex vivo skin permeation characteristics of the formulation with liposomes (LPS) and tinctures being used as reference preparations. Results According to a preferred formulation of dl-THP ETS [dl-THP 100 mg, vitamin E 1.3 mg, soybean lecithin 1 200 mg, cholesterol 120 mg, absolute ethanol 9 mL and citrate buffered saline (pH 3.0) 21 mL, 0.1 mol/L NaOH solution suitable quantity (to adjust the pH value to 5.5) ], the obtained dl-THP ETS had an elasticity index of (20.1 ± 1.1) mL, an average size of (85.8 ± 0.9) nm with a polydispersity index of (0.082 ± 0.003) and an entrapment efficiency of (81.7 ± 3.2)%. The cumulative permeated drug quantity per unit area (Qn) of dl-THP ETS in 24 h was (2 306.4 ± 592.3) μg/cm2 with no significant difference compared with the Qn of the LPS [(2 434.2 ± 564.4) μg/cm2] (P > 0.05) and about 4 times of that of the tincture [(633.1 ± 218.0) μg/cm2] (P < 0.05). And the averages of RSD of the Qn at each time point were (28.37 ± 10.9)% and (62.83 ± 44.1)% for the ETS and LPS, respectively, indicating that the Qn fluctuation among samples of the ETS was smaller than that of the LPS (P < 0.05). Average correlation coefficients of (0.968 ± 0.033) and (0.882 ± 0.078) (P < 0.05) were obtained for the ETS and LPS respectively when their 24 h permeation curves were fitted to linear relationship, indicating the permeation of the former was closer to zero-order kinetics than that of the latter. Conclusion The dl-THP ETS have a high elasticity, a suitable size, a high entrapment efficiency, and enhanced and stable percutaneous absorption in line with zero-order kinetics.

A Case of Gastric Ulcer Caused by NSAIDs Patches / 日本プライマリ・ケア連合学会誌

In general, when topical non-steroidal anti-inflammatory patches (hereinafter NSAIDs patches) are prescribed in clinical practice, adverse events, such as gastroduodenal ulcers, are not considered. However, patients often increase the number of NSAIDs patches they use in a single day even though they should only use 1 or 2 for local administration. Daily use of many NSAIDs patches (more than 4 large patches) may maintain the blood concentration of NSAIDs at a significantly level and cause adverse events similar to those by oral administration of standard-dose NSAIDs.We present a case of prolonged gastric ulcer caused by the daily use of many NSAIDs patches. In this case, Helicobacter pylori infection was negative and no oral NSAIDs were administered, and the discontinuation of NSAIDs patches resulted in the rapid healing of a gastric ulcer that was present for 2 years.

Percutaneous Absorption of Mupirocin Ointment in Vitro / 医药导报

Objective To compare the percutaneous absorption of experimentally prepared mupirocin ointment and commercially sold mupirocin ointment, and to study the dynamics mode of transdermal absorption of mupirocin ointment. Methods Inerstil ODS-SP column (4.6 mm× 150 mm,5 μm) was used with a mixture of 0.1 mol·L-1 sodium dihydrogen phosphate buffer solution (pH value was adjusted to 6.3 by 0.1 mol·L-1 sodium hydroxide solution) and acetonitrile (75:25) as a mobile phase by HPLC.The detection wavelength was set at 230 nm.The flow rate was 1.0 mL·min-1 .Improved Franz type diffusion cells were used for in vitro permeation studies and excised Obama Suckling pig skins in vitro were used as the transdermal barrier.The concentration of the receptor solution was determined by HPLC to investigate its cumulative permeation quantities at different time and the two sets of ointment were compared. Results The average recovery rate of hydrophilic medium was 99.4％,and RSD was 1.2％(n= 9).The average recovery rate of lipophilic medium was 99.0％,and RSD was 1.3％(n= 9).There was no significant difference of the concentration between two ointment within 12 h.The osmotic release of the drug of the sample and the reference preparation, which were in hydrophilic medium, was similar to that of the Zero equation, and roughly Higuchi equation in the lipophilic medium. Conclusion The results showed that the release behavior of mupirocin ointment followed Zero equation in the hydrophilic medium,and Higchi equation in the lipophilic medium.

Effect of azone on transdermal absorption of 6-gingerol / 中成药

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.

Study on biopharmaceutical properties of active fraction from Xiangfu Siwu Decoction by composite phospholipid liposome-based artificial skin membrane / 中草药

Objective: To evaluate the feasibility of the application of composite phospholipid liposome-based artificial skin membrane (CPLASM) for measuring biopharmaceutical properties of active fraction extracted from Xiangfu Siwu Decoction (XSD) via transdermal administration. Methods: The HPLC method was established for the determination of active ingredients (ferulic acid, tetrahydrocolumbamine, tetrahydropalmatine, senkyunolide I, and senkyunolide H) in active fraction of XSD. The oil/water partition coefficient values of these active ingredients were measured. The CPLASM was prepared to determine the in vitro permeability parameters of active fraction of XSD. The obtained parameters were further compared with those obtained by porcine ear skin. Results: The oil-water partition coefficients of ferulic acid, tetrahydrocolumbamine, tetrahydropalmatine, senkyunolide I, and senkyunolide H in active fraction of XSD (pH 5.5) were measured to be 1.220 ± 0.280, 0.670 ± 0.085, 0.920 ± 0.110, 1.040 ± 0.092, 1.030 ± 0.093 (n = 3), respectively. The permeability parameters of the active ingredients through porcine ear skin and CPLASM indicated a significant correlation (r > 0.9). Compared with the classical oil-water partition coefficients, the 6 h- cumulative permeation ratio of five active ingredients through CPLASM can be characterized as effectively predicting permeability parameters through porcine ear skin. Conclusion: The biopharmaceutical properties of active fractions from Chinese material medica can be effectively characterized by the application of CPLASM for the determination of in vitro permeability parameters of active ingredients.

Preparation and evaluation of triptolide and ferulic acid ethosomes / 中草药

Objective In order to optimize the preparation technology of triptolide and ferulic acid ethosomes and evaluate its characteristics of the in vitro transdermal penetration and the preparations performance using ethosome as carrier. Methods The compatibility ratio between triptolide and ferulic acid was determined by MTT. The triptolide and ferulic acid ethosomes were prepared with injection method based on the results of single factor experiments, Box-Behnken design was used to optimize the particle size, electric potential, and encapsulation efficiency (EE) of the ethosomes, and the in vitro release behavior prepared by the optimal formulation were studied. The in vitro transdermal absorption experiment was carried out in optimized Franz diffusion cells. Results The ratio of triptolide to ferulic acid was 1:100. The optimized prescription of the ethosomes was 20% ethanol, 2.2% phospholipid, 90 s ultrasonic time. The results showed that the appearance of the triptolide and ferulic acid ethosomes was clear liquid with blue opalescence in an average diameter of (46.75 ± 2.39) nm at potential of (-46.32 ± 3.76) mV, and the EE was (67.72 ± 1.10)%. The in vitro transdermal behaviors of ferulic acid and triptolide in the ethosomes were in line with the Higuchi equation. Conclusion The ethosomes has the advantages of small particle size, uniform distribution, good stability, and good transdermal absorption property, so as to provide the basis for the development of the transdermal preparation of the effective components of Tripterygium wilfordii.

Optimization of matrix formulation for Shaofu Zhuyu Cataplasm and research on its transdermal permeability in vitro / 中草药

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.

Preparation and transdermal permeation of triptolide and ferulic acid ethosomes gel / 中国中药杂志

The aim of this study was to prepare triptolide and ferulic acid ethosomes gel, investigate its transdermal permeation, and compare the results with ordinary gel and cream. Improved Franz diffusion cell method was used in the transdermal delivery experiment with rat abdominal skin as in vitro model. The receptor fluid at different time points was collected; ferulic acid concentration was determined by high performance liquid chromatography (HPLC) and triptolide concentration was determined by liquid chromatography-electrospray ionization mass spectrometry (LC-MS/MS). Then the penetration rate, transdermal volume and skin reserve of three dosage forms (hydroplasy gel, ordinary gel, and cream) to investigate the transdermal properties of ferulic acid and triptolide in vitro of triptolide and ferulic acid ethosomes gel. The results showed that the steady penetration rate of ferulic acid was 5.268 5, 8.990 9, 12.042 0 μg·cm⁻² ·h⁻¹ respectively in triptolide and ferulic acid ethosomes gel, ordinary gel and cream; the skin retention was (30.234 8±1.525 4), (20.402 6±0.402 6), (7.635 3±1.094 2) μg·cm⁻² . The steady-state permeation rate of triptolide was 67.238 0, 67.238 0 ng·cm⁻² ·h⁻¹ in triptolide and ferulic acid ethosomes gel, about 1.24 times of cream and 3.28 times of ordinary gel; the skin retention was (371.351 4±35.317 1) ng·cm⁻², about 3.35 times of cream and 5.25 times of ordinary gel. Therefore, the ethosomes gel showed good transdermal absorption property and it may be good for clinical safety administration.

Study on the in vitro Transdermal Absorption Properties of Galangin / 中国药房

OBJECTIVE:To investigate the in vitro transdermal absorption properties of galangin and effects of different pene-tration enhancers on its transdermal behaviors,and provide reference for developing skin preparations using galangin as APIs in the treatment of vitiligo. METHODS:HPLC was used to determine the galangin content. Using cumulative permeation rate (Q) and the transdermal rate(J)of galangin as indexes,the effect of absorption of receiving solution [20%,40% polyethylene glycol 400 (PEG400)solution and 30% ethanol solution] and rotating rate(200,300,400 r/min)on galangin in complete skin of mice were investigated,as well as the azone(1%,3%,5%)and propylene glycol(10%,20%,40%)alone or combination on its penetra-tion promotion. And the transdermal properties of galangin in complete skin,exfoliating skin,dermis skin of rats and mice were de-tected. RESULTS:The best permeability of complete skin of mice showed in 40% PEG400 solution at rotating speed of 300 r/min with 5% azone alone,J was 3.2570 μg/(cm2·h). Js of complete skin,exfoliating skin,dermis skin of mice were 2.7199,34.016, 33.874 μg/(cm2·h),respectively;and those of rats were 0.4996,9.5124,17.406 μg/(cm2·h). CONCLUSIONS:Galangin can penetrate the complete skin of mice and rats,however,the penetration quantity is far lower than exfoliating skin and dermis skin.

Studies on Skin Permeation in vitro of Phloretin and Ligustilide in Fufang Phloretin Cream / 中国药师

Objective: To determine the transdermal absorption of phloretin and ligustilide in Fufang phloretin cream.Methods: In vitro percutaneous absorption test using the Franz intelligent transdermal absorption apparatus was adopted, an HPLC method was used to determine the contents of phloretin and ligustilide in the accepting solution at different time points, and then the cumulative release amount and the total penetration amount were calculated to evaluate the percutaneous absorption behavior.Results: Phloretin and ligustilide showed a good linearity within the range of 0.044 2-4.42 μg·ml-1(r=0.999 9) and 0.048 7-4.87 μg·ml-1(r=0.999 9), respectively, the average recovery was 99.85% and 99.92%, and RSD was 0.67% and 0.66% (n=9), respectively.The in vitro permeation behavior of phloretin and ligustilide through the skin of rats fit Higuchi equations(r>0.9), suggesting a good linear correlation between the cumulatine penetration amount (Qn) and (time).Conclusion: Fufang phloretin cream has a good percutaneous permeation property in vitro.

Preparation and Transdermal Absorption in vitro of Piroxicam Nanostructured Lipid Carrier / 中国药师

Objective: To prepare piroxicam nanostructured lipid carrier and investigate its transdermal absorption behavior in vitro. Methods:Piroxicam nanostructured lipid carrier was prepared by a melt-emulsion ultrasonication and low temperature-solidifica-tion method. The physicochemical properties such as appearance, morphology, particle size distribution, PdI and zeta potential of pi-roxicam nanostructured lipid carrier were evaluated. The transdermal absorption in vitro was investigated using Franz diffusion cells. Results:Piroxicam nanostructured lipid carrier was clear and transparent with small spherical shape as seen under a transmission elec-tron microscope. The particle size distribution, PdI and zeta potential was (106. 4 ± 31. 6) nm, (0. 217 ± 0. 07) and ( -31. 6 ± 2. 5) mV, respectively. Piroxicam nanostructured lipid carrier had higher cumulative transdermal amount in 12 h than piroxicam solution. Conclusion:The nanostructured lipid carrier can remarkably improve piroxicam permeation into skin, which provides reference for the new dosage form for the topical use of piroxicam.

Preparation and in vitro Transdermal Study of Zolmitriptan-Diclofenac Microemulsion / 中国药房

OBJECTIVE:To prepare zolmitriptan-diclofenac microemulsion,and conduct quality evaluation and in vitro trans-dermal study. METHODS:Using solubility and microemulsion area in pseudo-ternary phase diagram as indexes,the types of oil phase and mixed emulsifier ratio of zolmitriptan-diclofenac microemulsion were screened;the microemulsion quality was inspected using particle size,Zeta potential,appearance and stability. HPLC was used to measure the contents of zolmitriptan and diclofenac. Transdermal diffusion test instrument was used,2 g microemulsion was smeared in cuticle of extracouporeal rats'skin,and cumula-tive transdermal rate in 24 h was determined. RESULTS:The microemulsion formulation was as follow as 10% oil phase(octanoic acid triglyceride),25% mixture emulgator [polysorbate 80-brij 97 (1:1)],8.3% propylene glycol and 25 mg zolmitriptan,1.25 mg diclofenac,and water adding to 100 mL. The average particle size of prepared microemulsion was(28.2±2.5)nm,Zeta poten-tial was(-3.25±0.33)mV,the appearance was rounding;the microemulsion showed no stratification or flocculation at room tem-perature after placed for 1 month. Contents of zolmitriptan and diclofenac were 0.248 mg/mL,12.46 mg/mL(n=3);24 h cumula-tive transdermal rates were 80%,75%. CONCLUSIONS:Zolmitriptan-diclofenac microemulsion is prepared,and its in vitro trans-dermal ability is good.

In vitro Transdermal Absorption of Xiaochuan Ointment / 中国药师

Objective:To study the transdermal absorption in vitro of sinapine thiocyanate,tetrahydropalmatine and asarinin in Xiaochuan ointment so as to offer reference for its clinical application.Methods:A Franz diffusion cells method with isolated rat skins was carried out to study the percutaneous rate of sinapine thiocyanate,tetrahydropalmatine and asarinin determined by LC-MS/MS.Results:With the increase of administration dosage,the cumulative penetration of sinapine thiocyanate,tetrahydropalmatine and asarinin showed few changes.The results showed that the transdermal behavior of sinapine thiocyanate fit to a Higuchi equation,and that of tetrahydropalmatine and asarinin fit zero-order process.The penetration rate of tetrahydropalmatine and asarinin respectively was 0.362×10-1 and 0.330×10-2 μg·cm-2·h-1.Conclusion:Xiaochuan ointment exhibits transdermal penetration and absorption properties,which provides evidence for its transdermal administration.

Evaluation of Rabbit Skin Irritation and in vitro Transdermal Absorption of Diclofenac Sodium Microemul-sion / 中国药房

OBJECTIVE:To investigate the property,skin irritation and in vitro transdermal absorption of Diclofenac sodium microemulsion(DS-ME),and to explore the feasibility of local external use of it. METHODS:The content of DS in DS-ME was determined by ultraviolet spectrophotometry. The distribution of particle size was determined by laser particle size analyzer. The ef-fects of DS-ME and blank micro-emulsion on normal skin of single administration,normal skin of multiple administration and dam-aged skin of single administration were investigated by rabbit skin irritation test. The transdermal parameters of DS-ME and commer-cially available DS gel through isolated skin of mice were compared by Franz diffusion cell. RESULTS:The prepared DS-ME was O/W microemulsion with particle size of(30.140±9.020)nm. Compared with blank ME,DS-ME had no significant difference in rabbit skin irritation score. Steady permeation rates of DS-ME and commercially available DS gel were 34.16 and 18.62 μg/(cm2·h), respectively;the permeation coefficient of them were 1.029 and 0.561 cm/h;the delay time were 0.124 2 and 0.367 2 h. CONCLU-SIONS:The particle size of DS-ME is small and not irritant to skin,and can improve transdermal absorption rate of DS.