Effect of Microemulsion on Content of Index Components in Different Phases of Zexietang Extract / 中国实验方剂学杂志

ObjectiveTo investigate the effect of microemulsion on the distribution of index components in different phases of Zexietang extract based on high performance liquid chromatography（HPLC） and phase separation process. MethodParticle size meter and transmission electron microscope were used to characterize the colloidal particles in blank microemulsion， aqueous extract of Zexietang and microemulsion extract of Zexietang. The phase separation process was established by high-speed centrifugation and dialysis， and based on this process， the aqueous extract and microemulsion extract of Zexietang were separated into the true solution phase， the colloidal phase and the precipitation phase， respectively. The contents of six components， including atractylenolide Ⅲ， atractylenolide Ⅱ， 23-acetyl alisol C， alisol A， alisol B and alisol B 23-acetate， were determined by HPLC with the mobile phase of water（A）-acetonitrile（B） for gradient elution（0-5 min， 40%-43%B； 5-20 min， 43%-45%B； 20-45 min. 45%-60%B； 45-75 min， 60%-80%B）. The solubility of the index components in water and microemulsion was determined by saturation solubility method. ResultThe colloidal particles in the aqueous extract， microemulsion extract and blank microemulsion were all spherical， and the particle size， polydispersity index（PDI） and Zeta potential of the colloidal particles were in the order of aqueous extract >microemulsion extract >blank microemulsion. The results of phase separation showed that the colloidal phase and the true solution phase could be completely separated by dialysis for 2.5 h， and the phase separation process was tested to be stable and feasible. Compared with the aqueous extract of Zexietang， the use of microemulsion as an extraction solvent could increase the contents of atractylenolide Ⅲ， 23-acetyl alisol C， atractylenolide Ⅱ ， alisol A， alisol B and alisol B 23-acetate by 3.75， 6.82， 35.47， 10.66， 35.41， 27.75-fold， and could increase the extraction efficiencies of the latter five constituents by 2.03， 1.15， 1.70， 6.43， 5.53 times. The solubility test showed that the microemulsion could significantly improve the solubility of atractylenolide Ⅱ， alisol A， alisol B and alisol B 23-acetate， but it had less effect on the solubility of atractylenolide Ⅲ and 23-acetyl alisol C. ConclusionMicroemulsion can improve the extraction efficiency and increase the distribution of the index components in the colloidal phase state of Zexietang to different degrees， providing a reference for the feasibility of microemulsion as an extraction solvent for traditional Chinese medicine.

Preparation of two tanshinone Ⅱ_A-astragaloside Ⅳ co-loaded nano-delivery systems and in vitro antitumor activity comparison / 中国中药杂志

This study screened excellent carriers for co-loading tanshinone Ⅱ_A(TSA) and astragaloside Ⅳ(As) to construct antitumor nano-drug delivery systems for TSA and As. TSA-As microemulsions(TSA-As-MEs) were prepared by water titration. TSA-As metal-organic framework(MOF) nano-delivery system was prepared by loading TSA and As in MOF by the hydrothermal method. Dynamic light scattering(DLS), transmission electron microscopy(TEM), and scanning electron microscopy(SEM) were used to characterize the physicochemical properties of the two preparations. Drug loading was determined by HPLC and the effects of the two preparations on the proliferation of vascular endothelial cells, T lymphocytes, and hepatocellular carcinoma cells were detected by the CCK-8 method. The results showed that the particle size, Zeta potential, and drug loading of TSA-As-MEs were(47.69±0.71) nm,(-14.70±0.49) mV, and(0.22±0.01)%, while those of TSA-As-MOF were(258.3±25.2) nm,(-42.30 ± 1.27) mV, and 15.35%±0.01%. TSA-As-MOF was superior to TSA-As-MEs in drug loading, which could inhibit the proliferation of bEnd.3 cells at a lower concentration and improve the proliferation ability of CTLL-2 cells significantly. Therefore, MOF was preferred as an excellent carrier for TSA and As co-loading.

Microemulsions Improve Topical Protoporphyrin IX (PpIX) Delivery for Photodynamic Therapy of Skin Cancer

Abstract We report here microemulsions (MEs) for topical delivery of protoporphyrin IX (PpIX) for Photodynamic Therapy (PDT) of skin cancers. Selected MEs consisting of Oil/Water (O/W) bicontinuous (BC) and Water/Oil (W/O) preparations were characterized as to pH, nanometric size, zeta potential, drug content, and viscosity. Sustained in vitro PpIX release was achieved from MEs 2A (O/W), 10B (BC) and 16B (W/O) through an artificial membrane for up to 24 h, characterizing MEs as drug delivery systems. None of these MEs showed permeation through the skin, demonstrating the required topical effect. After 4 h, in vitro retention of PpIX in the stratum corneum (SC) was higher from both ME 10B and control (PpIX at 60 µg/mL in PEG 300). However, in the Epidermis + Dermis ([Ep + D]), retention from ME 10B and ME 16B was ~40 times higher compared to control. Confocal Laser Scanning Microscopy (CLSM) showed higher fluorescence intensity in the SC for both control and ME 10B, whereas ME 10B fluorescence was higher in [Ep+D]. The results indicate that ME 10B is suitable for PpIX encapsulation, showing good characteristics and a localized effect for a potential delivery system for PDT-associated treatments of skin cancers.

Preformulation studies for the development of a microemulsion formulation from Ambrosia peruviana All, with anti-inflammatory effect

Abstract Natural products are considered an important source of the therapeutic arsenal currently available. Among these alternatives are the seeds of Ambrosia peruviana (altamisa), whose extract has shown an anti-inflammatory effect. The main objective of this work was to perform a preformulation study of Ambrosia peruviana seeds ethanolic extract, where the main factors that affect the physical, chemical, and pharmacological stability of the extract were evaluated, as well as a compatibility study by differential scanning calorimetry (DSC) analysis against different excipients. A dry extract was obtained by rotary evaporation of the seeds macerated with 96% ethanol. The anti-inflammatory activity was determined by measuring its effect on NO production in RAW 264.7 macrophages, stimulated with LPS. The results showed that the dry extract maintained its stability over time when stored at a temperature of 4 and 25ºC, demonstrating its biological activity, the content of phenolic compounds, and its physicochemical parameters remain practically invariable. However, when exposed to high temperatures (60 ºC) it was affected. The thermal analysis revelated that the behavior of most of the selected excipients and the dry extract was maintained, which indicates that it did not present incompatibilities, therefore they can be candidates for formulating a microemulsion.

Preparation and evaluation of sirolimus sustained release tablets based on mesoporous silicon loaded self-microemulsion / 药学学报

Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the Cmax of the sustained-release tablets decreased by 49.47%, the Tmax of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.

Preparation of Angelica•Cinnamomum self•microemulsion drug delivery system based on the concept of “unifica- tion of drugs and excipients ” / 中国药房

OBJECTIVE To prepare Angelica•Cinnamomum（Angelica sinensis-Cinnamomum cassia ）self•microemulsion drug delivery system （AC•SMEDDS），and to optimize its formulation and characterize its preparation . METHODS Using Angelica• Cinnamomum mixed volatile oil as oil phase and model drug ，on the basis of selecting emulsifier and co -emulsifier and the optimization of their mass ratio range ，the formulation was optimized with central composite design •response surface methodology using the ratio of oil phase （Angelica•Cinnamomum mixed volatile oil ），mass ratio of emulsifier and co -emulsifier as factors ，the comprehensive score of volatile oil content ，particle size and emulsifying time as index . Morphology，particle size ，drug loading ， entrapped efficiency and stability of optimized AC•SMEDDS were characterized . RESULTS The optimum formulation of AC•SMEDDS contained the ratio of oil phase was 30%，and the mass ratio of emulsifier （EL•40）and co -emulsifier（ethanol）was 9∶1. Results of validation tests showed that the average particle size of AC•SMEDDS was （148.33±1.53）nm，and emulsifying time was （18.44±0.11）s. The comprehensive score was 0.68，relative deviation of which from the predicted value （0.70）was 2.86%. AC•SMEDDS prepared by optimal formulation was faint yellow ，uniform and transparent liquid ，and spherical particals with translucent edge were observed under transmission electron microscope . Calculated by ligustilide and cinnamaldehyde ，the drug loading was （7.58±0.03） and （4.17±0.01） mg/g，and entrapped efficiency was （93.25±0.01）% and （88.89±0.02）% ， respectively. No stratification or precipitation occurred after centrifugation at the speed of 10 000 r/min or placing within 7 （No.2019-0520） days at 4 and 25 ℃ . The contents of ligustilide and cinnamaldehyde were stable . Its particle size had no significant change after 50，100 and 200 times dilution by purified water . CONCLUTIONS AC•SMEDDS is prepared successfully and its formulation is optimized . The stability of the preparation is good .

Comparison of Microemulsion and Solvent Evaporation Technique for Solubility Enhancement of Amlodipine Besylate

@#Introduction: Amlodipine besylate is a calcium channel blocker indicated for hypertension and angina. It is described as slightly soluble in water and due to its limited solubility, it may result in poor bioavailability. The aim of this study is to enhance the solubility of amlodipine besylate using solvent evaporation method and microemulsion technique and to compare the two methods. Method: Solid dispersions (SD) of amlodipine besylate were developed by employing solvent evaporation method. PEG6000 was the polymer of choice and different drug:polymer ratios were used. Evaluation of the prepared SDs include solubility studies, dissolution studies and scanning electron microscopy (SEM). As for the microemulsion technique, microemulsions were prepared by phase titration method and the optimized microemulsion formulation was then characterized for solubility studies and dissolution studies. Results: SD3 with drug:polymer ratio of 1:4 achieved the highest solubility which was 96.97 mg/ml ± 0.92 whereas the solubility of the optimized microemulsion was found to be 112.54 mg/ml ± 0.92. In solvent evaporation method, as the drug:polymer ratio increases, the solubility and dissolution rate of SDs increases. Conclusion: The two methods had significantly enhance the solubility of amlodipine besylate however the microemulsion technique showed better solubility profile.

New topical microemulsions of etofenamate as sufficient management of osteoarthritis

Abstract In this study, microemulsions containing etofenamate were prepared and evaluated as dermal delivery carriers. The developed microemulsions consist of oleic acid, Span 80, Tween 20, Cremophor EL, Transcutol and ethanol. The percentage of etofenamate loading in the microemulsions was 5% (w/w). The characterization of formulations included droplet size, zeta potential, pH, conductivity, PDI, refractive index and viscosity. Moreover, ex vivo penetration study was carried out using mice abdominal skin. The developed formulations were analyzed for their cytotoxicity via MTT assay and tested for their anti-inflammatory properties opposed to LPS-stimulated nitrite prοduction in RAW 264.7 cells. As ideal formulation, M2ETF, was chosen due to its greater permeation, lower penetration as well as higher anti-inflammatory

Compatibility and efficiency of preservatives in emulsive cosmetics containing high surfactant content

Abstract The objective of this study was to determine the influence of nonionic surfactants on the effectiveness of preservatives used in emulsions containing high surfactant content. Mixtures of different concentrations were prepared between polyethoxylated (40) hydrogenated castor oil (PHCO) and polyoxyethylene sorbitan monooleate (PSO), with methylparaben, phenoxyethanol, methylparaben, ethylparaben, propylparaben, and isobutylparaben (PMEPBI) blend, phenoxyethanol and benzoic acid (BP) blend, and phenoxyethanol and caprylyl glycol (PC) blend. Subsequently, the compatibility of the formulation ingredients and the effectiveness of the preservatives were evaluated by the challenge test. It was found that PHCO and PSO inactivated the antimicrobial action of methylparaben and PMEPBI. Paraben-free preservatives BP and PC had less influence on surfactants than systems containing parabens. When incorporated into microemulsions and nanoemulsions containing 40% and 20% surfactants, methylparaben and BP 0.2% and 0.5% were only effective against Aspergillus niger. The PMEPBI 0.2% was effective as a preservative in nanoemulsified formulations against A. niger, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The results demonstrate that the efficacy of the preservative system in formulations containing nonionic surfactant excipients depends on the type of excipient, the components of the formulation, the preservative systems composition, the excipient to preservative ratio, and the availability in the formulation.

Semisolid formulations based on solid-in-oil-in-water systems containing proteins

Abstract In recent years, improvements have been made, through biotechnological processes, in the production and development of peptides capable of increasing collagen and elastin synthesis for anti-aging skin care. However, proteins have many limitations due to their structural, chemical and physical fragility to external aggressions, which may cause conformational changes, leading to loss of biological activity. Therefore, it is important to create delivery systems that protect these biomolecules from damage, allowing them to reach their target. This work aimed to develop a system able to carry bovine serum albumin (BSA), used as a model of a protein, and to incorporate this system in a semisolid formulation suitable for skin application. A microemulgel based on a solid-in-oil-in-water (S/O/W) microemulsion was prepared. Firstly, the association efficiency (AE) of lyophilized BSA-sucrose ester complex and the size of S/O nanodispersion were assessed; then, the characterization and stability evaluation of the final semisolid formulation through evaluation of pH, texture and rheological behavior were performed. The average value of AE was 54.74% ± 2.17. It was possible to develop an S/O/W microemulsion, which allowed the subsequent development of an S/O/W microemulgel that assured suitable pH, texture and rheological characteristics for skin application.

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.

Formulation and antimicrobial activity evaluation of a 0. 2% chlorhexidine canine mouthwash with essential oils / Formulación y evaluación de la actividad antimicrobiana de un enjuague bucal canino de clorhexidina al 2% y aceites esenciales

Background: Periodontal disease is the infection and inflammation of the gums, bones, and tissues involved in teeth support, and it is one of the most common diseases affecting pet dogs. Essential oils have shown antimicrobial activity against bacteria causing periodontal disease; therefore, they are considered potential therapeutic agents. Objectives: The main objective was to formulate and evaluate the antimicrobial activity of a 0.2% chlorhexidine canine mouthwash with essential oils. Methods: Three microemulsion formulations were obtained by constructing a pseudo-ternary phase diagram using the phase titration method. Different surfactant agents were evaluated, and hydrogenated castor oil was selected as the emulsifier agent. The antimicrobial activity of oregano essential oil (Origanum vulgare), thyme essential oil (Thymus vulgaris), and the three formulations were evaluated against Staphylococcus aureus, Streptococcus mutans, Streptococcus salivarius, and Escherichia coli. Results: Pure thyme and oregano essential oils showed higher antimicrobial activity than a 0,2% chlorhexidine solution. The formulations with essential oils plus chlorhexidine and chlorhexidine alone showed antimicrobial activity. The formulation containing only essential oils did not show antimicrobial activity. Conclusions: A canine mouthwash was formulated with chlorhexidine and thyme, and oregano essential oil. Based on the evaluation of antimicrobial activity, two of the proposed formulations could be a therapeutic option to reduce the risk and prevent periodontal disease in canines

Antecedentes: La enfermedad periodontal es la infección e inflamación de las encías, huesos y tejidos que brindan soporte a los dientes, es una de las enfermedades más comunes que afectan a los perros de compañía. Los aceites esenciales han mostrado actividad antimicrobiana contra las bacterias que causan la enfermedad periodontal; por lo tanto, son considerados como potenciales agentes terapéuticos. Objetivos: El objetivo principal de este trabajo fue formular y evaluar la actividad antimicrobiana de un colutorio canino de clorhexidina al 0,2% con aceites esenciales. Métodos: Se obtuvo tres formulaciones en microemulsión mediante la construcción de un diagrama de fase pseudoternario por el método de titulación de fase. Se evaluaron diferentes tensioactivos y se seleccionó el aceite de ricino hidrogenado como agente emulsificante de la formulación. La actividad antimicrobiana del aceite esencial de orégano (Origanum vulgare), el aceite esencial de tomillo (Thymus vulgaris) y las tres formulaciones fue evaluada contra Staphylococcus aureus, Streptococcus mutans, Streptococcus salivarius y Escherichia coli. Resultados: Los aceites esenciales puros de tomillo y orégano mostraron una mayor actividad antimicrobiana que una solución de clorhexidina al 0,2%. Las formulaciones con aceites esenciales más clorhexidina y únicamente clorhexidina mostraron actividad antimicrobiana. Mientras que la formulación que contiene solo aceites esenciales no mostró actividad antimicrobiana. Conclusión: Se formuló un enjuague bucal canino con clorhexidina y aceite esencial de tomillo y orégano. Según la evaluación de la actividad antimicrobiana, dos de las formulaciones propuestas podrían ser una opción terapéutica para disminuir el riesgo y prevenir la enfermedad periodontal en caninos

Preparation and quality evaluation of fluorocarbon microemulsion-based gel loaded with both 5-aminolevulinic acid and carbon dioxide / 药学学报

To improve the efficacy of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT), a fluorocarbon microemulsion-based gel (FMBG) loaded with both 5-ALA and carbon dioxide (CO2) was prepared in this study. Its physical and chemical properties such as particle size, zeta potential, morphology, pH value and viscosity were characterized. Acid-base titration experiment was used to determine the CO2 loading, a fluorescence derivatization method was established to determine the content of 5-ALA, and the confocal laser scanning microscope and Franz diffusion cell method were carried out to investigate its transdermal ability. Through the laser speckle contrast imaging, the CO2-affected blood flow perfusion of skin was measured. Finally, the skin irritation test was tested by hematoxylin-eosin staining (H&E) method. These results showed that the prepared FMBG was a milky white gel, with an average particle size of 202.4 nm, a zeta potential of -25.3 mV, a pH of 6.0, and a viscosity of 1 062.0 mPa·s. It can be stored stably for seven days at room temperature. The 5-ALA content of FMBG was measured to be approximately equal to 20% (w/w). At room temperature and normal pressure, the CO2 loading content of FMBG was 5.016 mg·L-1, which was 1.5 times as much as that of water. The transdermal absorption experiment and blood perfusion results showed that the FMBG can effectively enable the transdermal delivery of 5-ALA and CO2, and significantly increased the blood perfusion of skin. H&E staining results indicated that FMBG had negligible skin irritation (all animal tests were approved by the Ethics Committee of 900 Hospital of the Joint Logistics Team). In this study, a safe and stable FMBG loaded with both 5-ALA and CO2 was successfully prepared. It was suitable for transdermal application, having the potential of enhancing the efficacy of 5-ALA-mediated PDT.

Microemulsion assisted transdermal delivery of a hydrophilic anti-osteoporotic drug: Formulation, in vivo pharmacokinetic studies, in vitro cell osteogenic activity

Gastrointestinal adverse effects such as esophageal irritation and ulcers are the major disadvantages of the oraladministration of alendronate (ALD) and nitrogen-containing bisphosphonate. We hypothesized that the transdermaldelivery of ALD via water in oil (w/o) microemulsion might help to prevent the aforementioned side effects withoutcompromising the efficacy. The pseudo-ternary phase diagrams were constructed with varying ratios of surfactantmixture and oil to recognize the concentration range of excipients required to form a monophasic microemulsion.Globule size, morphology transmission electron microscopy, and thermal behavior differential scanning colorimetryof drug-loaded microemulsion were investigated. The in vitro permeation studies revealed significantly enhancedpermeation of ALD through microemulsion than pure solution across the rat skin (p < 0.01). In an in vivopharmacokinetic study in Wistar rats, microemulsion achieved around two folds higher bioavailability than pure drugsolution (p < 0.05) when given in equal doses (30 mg/kg). Cell viability assay with human osteoblastic osteosarcoma(MG-63) cells exhibited the positive effects of ALD microemulsion on cell growth. Moreover, alkaline phosphataseand mineralization studies proved that microemulsion as a carrier retains distinct osteogenic properties of ALD.Overall, these outcomes demonstrated that the w/o microemulsion as a transdermal carrier is a promising approach forthe effective delivery of ALD, bypassing the adverse effects associated with oral administration

Development And Validation Of A Simple Hplc Method For Estimation Of Mycophenolate Mofetil In Microemulsion Formulation

Objective: The present study deals with the development, validation and application of a simple, precise and accurate HPLC method for the determination of mycophenolate mofetil in pharmaceutical formulations and microemulsions. Methods: In this method, a simple isocratic mobile phase composition of methanol and water (75:25 v/v) pumped at 1 ml/minute flow rate through Phenomenex C18 column (dimension: 250 4.6 mm and 5 µm particle size) was used. Injection volume was 20 µl and analysis of mycophenolate mofetil was carried out at 250 nm. Results: The coefficient of regression was found to be 0.9996, indicating the linearity of the developed method within a range of 0.1 to 10 µg/ml. The limit of detection (LOD) and the limit of quantization (LOQ) were found to be 3.660ng/ml and 11.091ng/ml, respectively. The results showed that % deviation for change in compositions of the mobile phase, flow rate and temperature was within a range of-5.51 to 10.99%,-3.70 to 8.80% and-5.29 to 10.90%, respectively. The method seemed sensitive to change of temperature (±5 ○C) and methanol composition (±2%) as the results were at the boundary limit of 10% deviation. Conclusion: A simple, precise and accurate HPLC method for the determination of drug content from microemulsion has been developed and validated in accordance with ICH guidelines.

Development Of Microemulsion Formulation For Oral Delivery Of Rosuvastatin Calcium

The purpose of conducting this study was to prepare an oral microemulsion formulation of Rosuvastatin calcium (RC) to improve its water solubility. Oil in water microemulsion was formulated using Oleic acid, Tween 80 and Polyethylene Glycol-400(PEG-400) as oil, surfactant and co-surfactant, respectively. The ideal proportion of surfactant: co-surfactant (Smix) was chosen by constructing pseudoternary diagrams. The microemulsion formulations which proved to be stable after thermodynamic stability testing were further evaluated for physical characteristics. Selected formulations were evaluated for droplet size, zeta potential, polydispersity index, viscosity and % drug content. The results were suggestive that optimized microemulsion formulation (F2) was thermodynamically stable and clear having a droplet size of 74.29 nm and zeta potential of -18.44. In vitro dissolution study for optimized microemulsion was performed using a dialysis bag method and cumulative % drug release was determined. The result from the release study was indicative of improved solubility of Rosuvastatin calcium which may serve to boost up the oral bioavailability of drug.

Preparation and Evaluation of Weisu Microemulsion-Ion Sensitive Gel / 中国药学杂志

OBJECTIVE: To design and evaluate the formula of Weisu microemulsion-ion sensitive gel. METHODS The prescription of microemulsion-ion sensitive gel was conducted on the basis of single factor method and pseudotemary phase diagram method combining with central composite design-response surface methodology. The final formulation was evaluated by particle size, viscosity, potential, contents of naringin, hesperidin and neohesperidin. RESULTS: The optimum prescription ratio of Weisu microemulsion-ion sensitive gel was as following:volatile oil 3 g, RH-40 9 g, PEG-400 3 g, 0.3% deacetylated gellan gum made into 333 mL microemulsion gel. The results of physicochemical properties showed that microemulsion gel appearance was clear. The particle diameter was 20.14 nm. The Zeta potential was -4.04 mV. pH value was 5.43. The contents of naringin, hesperidin and neohesperidin are respectively 6.122 4, 2.094 1, 4.277 mg•mL-1. CONCLUSION: The preparation process of Weisu microemulsion gel is reasonable and feasible. The prepared microemulsion gel is system are stable.

Preparation and Formulation Optimization of Ketoprofen Microemulsion-based Gel / 中国药学杂志

OBJECTIVE: To prepare the ketoprofen microemulsion-based gel in order to expand its drug loading and increase the transdermal permeability. METHODS: The proportion range of oil phase/surfactant in ketoprofen microemulsion were screened by the pseudo-ternary phase diagram. Optimization of formulation for microemulsion gels was conducted by central composite design-response surface methodology with the cumulative permeation quantity across in vitro rat skin and time-lag as evaluation indexes.The transdermal performance of self prepared gel was compared with the commercially available gel. RESULTS: The optimal oil phase, surfactant and cosurfactant of ketoprofen microemulsion were oleic acid, polyoxy ethylene castor oil (EL-35) and ethanol, respectively.The optimal microemulsion formulation was 1.35% oleic acid, 10.8% EL-35, and 9% ethanol by central composite design experiment. The cumulative penetration quantity in 24 h reached 562.82 μg•cm-2 in vitro rat skin was 1.35 times as much as commercially available gel. CONCLUSION: The ketoprofen microemulsion-based gel prepared in this study has good permeability, which lay the foundation for development of the gel.

Dangshen Yuanzhi Powder microemulsion attenuates learning and memory impairment in Alzheimer’s disease model mice / 中草药

Objective: To observe the effects of Dangshen Yuanzhi Powder microemulsion on protein expression of AchE and ChAT, and the contents of Ach and AchE in brain tissue of Alzheimer’s disease model mice and analyze its mechanism based on cholinergic theory. Methods: Mice were divided into control group, model group, BME group, Piracetam group, water extractant group and microemulsion extractant group, with 15 mice in each group. Alzheimer’s disease mice model was established by intraperitoneal injection with D-gal and NaNO2. Meanwhile, each group was given by gavage for six weeks with distilled water, BME, Piracetam tablets, water extractant and microemulsion extractant. Water maze was used to conduct behavior study. Contents of Ach and AchE in brain tissue were also measured. HE staining was used to observe pathological changes and IHC staining was used to detect expression of AchE and ChAT in hippocampal CA1 region and cerebral cortex of mice. Results: Compared with the model group, learning and memory abilities of mice were significantly improved (P < 0.05), content of Ach was significantly improved (P < 0.01), content of AchE was significantly decreased (P < 0.01), pathological changes of hippocampal CA1 region and cerebral cortex were improved, AChE expression was significantly downregulated (P < 0.01), and ChAT expression was markedly upregulated (P < 0.01) in microemulsion extractant group. Conclusion: Dangshen Yuanzhi Powder microemulsion can control the progression of Alzheimer’s disease by upregulating ChAT expression and inhibiting AChE expression in hippocampal CA1 region and cerebral cortex of mice.

Preparation, quality evaluation and cell uptake of 1,8-cineole self-microemulsion drug delivery system / 中草药

Objective: To optimize the formulation of 1,8-cineole self-microemulsifying drug delivery system (1,8-Cin-SMEDDS), characterize it and investigate its cell uptake. Methods: By drawing pseudo-ternary phase diagram, the effective self-emulsifying region of 1,8-Cin-SMEDDS was determined, and the preliminary prescription was screened. Taking the particle size and drug loading as the index, the central composite design-response surface method was used to optimize and verify the prescription. Fluorescence microscope was used to observe the uptake of human umbilical vein endothelial cells (HUVEC) injured by high glucose. Results: The results showed that the best prescription of 1,8-Cin-SMEDDS was a mixture of soybean oil (7.5%) and 1,8-Cin (22.5%), HS15 (56%) as emulsifier, ethanol (14%) as co-emulsifier, and dripping pure water to 8 mL to obtain a translucent slightly bluish emulsion. The appearance of spherical droplets was observed by transmission electron microscope, and the average particle size and Zeta potential measured by laser particle size Zeta tester was (131.68 ± 1.44) nm and (-10.03 ± 1.63) mV, respectively; The entrapment efficiency estimated by HPLC was (99.890 ± 0.012)%, and the drug loading was (224.750 ± 0.028) mg/g. The results of HUVEC cell uptake assay showed that the uptake of 1,8-Cin-SMEDDS by cells was higher than that of free 1,8-Cin. Conclusion: The preparation method of 1,8-Cin-SMEDDS is simple and reproducible. The obtained method has good appearance, high entrapment efficiency, stable physical, and chemical properties, which can also promote cell uptake.