Research progress in new formulations of norcantharidin / 药学实践杂志

Objective To review the research progress in new formulations of norcantharidin. Methods The foreign and domestic literature search in the new formulations of norcantharidin was conducted. The research and development of norcantharidin formulations were summarized and commented. Results The drug delivery systems, such as microspheres, nanoparticles, liposomes, and microemulsions, have great development potential as the new formulations for norcantharidin. Conclusion Norcantharidin is an excellent anti-tumor drug. The traditional injections and tablets have serious side effects in clinical application. The new formulations reduced the renal and urinary toxicity and side effects. Those formulations provided better therapeutic effects as target medication. Therefore, the new norcantharidin formulations have great development prospects.

monitoring of the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET

Microemulsions are promising drug delivery systems for the oral administration of poorly water-soluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized, especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET spectra indicated micelles with smaller particle sizes were generated during lipolysis, which could be affected by CaCl, bile salts and lecithin. Then, the effect of mucus on the structural change of lipolysed microemulsions was studied. The results of SAXS and FRET indicated that the liquid crystalline phases disappeared, and more micelles were generated. In summary, we studied the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET, and successfully monitored the appearance and disappearance of the liquid crystalline phases and micelles.

Efecto de Microemulsiones de Aceites Esenciales Sobre el Eritrocito Humano y Bacterias Patógenas / Effect of Microemulsions of Essential Oils on Human Erythrocyte and Pathogens Bacteria

RESUMEN: El objetivo del presente trabajo fue evaluar el efecto de las microemulsiones de aceite esencial de romero (AER) y árbol de té (AET) sobre el eritrocito humano y microorganismos patógenos. Para ello, se elaboraron microemulsiones de AER y AET al 8.0% (v/v), 5.0% (v/v) y 2.5% (v/v). Las microemulsiones fueron probadas sobre el eritrocito humano para determinar el porcentaje de hemólisis, el porcentaje de inhibición de hemólisis y su actividad antibacterial contra E. coli O157:H7 y S. aureus. Las microemulsiones con AER no presentaron actividad hemolítica significativa, caso contrario con las microemulsiones de AET al 8.0% (≈70%) y 5.0% (33%) que presentaron mayor actividad hemolítica. Las microemulsiones de AER protegieron significativamente al eritrocito contra la presencia de radicales libres, en comparación con aquellas de AET (p< 0.05). Además, las emulsiones de AET al 8.0% mostraron efectos antibacterianos contra E. coli O157:H7 y S. aureus mientras que AER al 8.0% solo mostraron efecto contra E. coli O157:H7. La limitante del estudio fue que no utilizamos células nucleadas para establecer si los aceites esenciales dañan el material nuclear. Sin embargo, observamos que el tipo y la cantidad de aceite utilizado pueden tener implicaciones serias sobre la membrana eritrocitaria. Se concluye que las microemulsiones de AER presentaron mejor efecto protector eritrocitario, mientras que las microemulsiones de AET presentaron mejor actividad antibacterial contra las bacterias estudiadas, pero con mayor efecto tóxico sobre el eritrocito.

ABSTRACT: The aim of the study was to evaluate the effect of microemulsions of rosemary (AER) and tea tree (AET) essential oils on human erythrocyte and pathogen bacteria. Microemulsions of each oil were prepared at 8.0% (v/v), 5.0% (v/v) and 2.5% (v/v), and they were tested on human erythrocyte to determine the hemolysis percentage, hemolysis inhibition percentage and the antibacterial capacity against E. coli O157:H7 and S. aureus. All AER microemulsions showed no significant hemolytic activity. On the contrary, AET microemulsions showed hemolytic effect but those in concentrations of 8.0% (≈70 %) and 5.0% (33%) showed the highest effect. In addition, AER microemulsions showed protective effect against free radicals in comparison with the AET microemulsions (p< 0.05). On the other hand, the AET microemulsion at 8.0% showed antibacterial effect against E. coli O157:H7 and S. aureus, and the AER at 8.0% showed antibacterial effect against E. coli O157:H7. The limitation of this study was that nucleated cells were not used to observe the damage of the essential oils on nuclear material. However, the observed damage of erythrocyte's membrane is depending on type and amount of used oil. Therefore, it can be concluded that the AER microemulsions showed better protective effect of erythrocytes, while AET microemulsions showed better antibacterial effect against the tested bacteria, although with toxic effect on the erythrocytes.

Preparation of microemulsions loaded with total flavonoids from Potentilla discolour and the therapeutic effect on diabetic mice / 中成药

AIM To prepare the microemulsions loaded with total flavonoids from Potentilla discolor Bunge and to evaluate the therapeutic effect on diabetic mice.METHODS Total flavonoids,the extract from P.discolor by 70％ ethanol,were made into microemulsions after purification with.macroporous resin.With types and amount of oil phase,emulsifier and co-emulsifier,and addition amount of total flavonoids as influencing factors,together with drug loading,encapsulation efficiency,particle size and Zeta potential as evaluation indices,the formulation was optimized by drawing pseudo-ternary phase diagram.By establishing diabetic mouse models induced by streptozotocin (STZ) and high fat diet,the obtained microemulsions' effects on fasting blood glucose,oral glucose tolerance (OGT),insulin,glycosylated serum protein (GSP),triglyceride (TG),total cholesterol (TC),low density lipoprotein (LDL),high density lipoprotein (HDL),superoxide dismutase (SOD) and malondialdehyde (MDA) in mice were investigated.RESULTS The optimal formulation was determined to be 400 mg for isopropyl myristate (oil phase) amount,400 mg for Cremophor RH 40 (emulsifier) amount,200 mg for polyethylene glycol 400 (coemulsifier) amount,and 80 mg for addition amount of total flavonoids.The spherical-like and uniformly-sized microemulsions shared average drug loading of (7.28 ± 0.12)％,encapsulation efficiency of (91.79 ± 1.02)％,particle size of (36.79 ±0.17) nm and Zeta potential of (-15.77 ±2.89) mV.They could significantly reduce fasting blood glucose level,promote insulin secretion,regulate blood lipid,increase SOD activity,and decrease MDA level in diabetic mice.CONCLUSION Once prepared into microemulsions,the total flavonoids from P.discolor demonstrate an obviously enhanced activity in reducing blood glucose.

Application of New Carriers in Transdermal Drug Delivery System / 中国药师

Compared with traditional oral administration and parenteral administration, transdermal administration has such fea-tures as convenient application, high local drug concentration and strong security. This paper reviewed the composition, characteristics and applications of new carriers ( microemulsions, ethosomes, transfersomes, niosomes, proliposomes, gels and so on) in transdermal drug delivery system with increased drug transdermal transport efficiency in recent years. The advantages of the new transdermal drug delivery carriers make them possess high research value and broad development space.

Organic cocoa extract -loaded surfactant-based systems intended to skin bioadhesion

ABSTRACT This study was to develop, characterize, and evaluate the physical-chemical stability, in vitro antioxidant activity and in vitro safety profile of liquid crystalline systems (LCS) and microemulsions (MEs) with and without organic cocoa (OC) extract. LCS stabilized by surfactant polyoxyethylene 20 cetyl ether, containing water and oleic acid were studied. LCS and MEs were characterized using polarized light microscopy, small angle X-ray scattering, rheology and in vitro bioadhesion, and were evaluated for a period of 30 days by visual aspects, centrifuge test, pH value and relative density. PLM and SAXS assays showed the presence of domains of MEs, cubic and hexagonal mesophasephases, varying the proportions of the components of the formulations; where in the addition of the extract did not change rheological behavior of the formulations. All of the formulations were stable in the period analyzed and presented higher bioadhesive strength. In vitro antioxidant activity suggests that LCS and MEs presented a high capacity to maintain the antioxidant activity of OC extract. The results showed that the incorporation of OC in LCS improved the safety profile, according to cytotoxicity assays of systems may be a promising platform to OC extract for topical application for the potential treatment of skin disorders.

Preparation and Characterization of Resveratrol Microemulsions / 中国药师

Objective:To prepare resveratrol microemulsions by high pressure homogenization method and characterize the microe-mulsions. Methods:Using the particle size, polydispersion index and encapsulation efficiency as the indicators, the independent varia-bles of the preparation were inspected, and the microemulsions were characterized. The stability of resveratrol microemulsions was stud-ied by long term stability test preliminarily. Results:The mean particle size, polydispersion index and zeta potential of resveratrol mi-croemulsions was (231 ± 37. 8) nm, 0. 228 ± 0. 047 and ( -42. 5 ± 4. 3) mV, respectively. The microemulsions were found to be small and spherical with smooth surface under a transmission electron microscope. Long term stability studies showed that the microe-mulsions were stable in 3 months after stored at 25℃. Conclusion:The preparation process of high pressure homogenization method for resveratrol microemulsions is simple and feasible.

Application of Microemulsions on Transdermal Delivery Systems / 中国药师

Objective:To review the application of microemulsions as vehicles in transdermal delivery systems. Methods:Based on the recently published papers, the research on the application of microemulsions was classified and summarized. Results: Microe-mulsions is extensively applied as drug vehicles due to the ability of solubilization, drug permeation enhancement and efficacy improve-ment. Conclusion:Microemulsions as promising vehicles for transdermal delivery show a good application prospect.

Validation of high-performance liquid chromatographic method for analysis of fluconazole in microemulsions and liquid crystals

In recent decades, there has been a significant increase in the incidence of fungal diseases. Certain fungal diseases cause cutaneous lesions and in the usual treatment, generally administred orally, the drug reaches the site of action with difficulty and its concentration is too low. An approach much explored in recent years is the development of nanotechnology-based drug delivery systems, and microemulsions (ME) and liquid crystals (LC) are promising. ME and LC were developed with oleic acid or copaiba oil as the oil phase, propoxyl (5OP) ethoxyl (20 OE) cetyl alcohol as surfactant and water. An analytical method to assess the incorporation of fluconazole (FLU) in the systems under study was validated according to guidelines of the International Conference on Harmonization (ICH) guidelines and the Brazilian Food, Drug and Sanitation Agency (ANVISA). The method was conducted on a C18-RP column (250 × 4.6 mm i.d.), maintained at room temperature. The mobile phase consisted of acetonitrile and water (50:50, v/v), run at a flow rate of 1.0mL/min and using ultraviolet detection at 210nm. The chromatographic separation was obtained with a retention time of 6.3min, and was linear in the range of 20-400 µg/mL (r2=0.9999). The specificity showed no interference of the excipients. The accuracy was 100.76%. The limits of detection and quantitation were 0.057 and 0.172 µg.mL-1, respectively. Moreover, method validation demonstrated satisfactory results for precision and robustness. The proposed method was applied for the analysis of the incorporation of FLU in ME and LC, contributing to improve the quality control and to assure the therapeutic efficacy.

Nas últimas décadas, houve aumento significativo na incidência de doenças fúngicas. Certas doenças fúngicas provocam lesões cutâneas, sendo que no tratamento usual, geralmente administrado por via oral, o medicamento chega ao local de ação com dificuldade, em concentração muito baixa. Uma abordagem muito explorada nos últimos anos é o desenvolvimento de sistemas de administração de fármacos baseados em nanotecnologia, como as microemulsões (ME) e cristais líquidos (LC). ME e LC foram desenvolvidos com o ácido oleico ou óleo de copaíba como fase oleosa, álcool cetílico propoxilado (5 OP) e etoxilado (20 OE) como tensoativo e água. Método analítico para avaliar a incorporação de fluconazol (FLU) nos sistemas em estudo foi validado de acordo com as diretrizes da Conferência Internacional de Harmonização (ICH) e Agência Nacional de Vigilância Sanitária (ANVISA). O método foi desenvolvido empregando coluna C18-RP (250 x 4,6 mm id), mantida à temperatura ambiente. A fase móvel consistiu de acetonitrila e água (50:50, v/v), executado a uma taxa de fluxo de 1,0 mL/min e com detecção ultravioleta a 210 nm. A separação cromatográfica foi obtida com o tempo de retenção de 6,3min, e mostrou-se linear no intervalo de 20-400 µg/mL (r2=0,9999). Pelo estudo de especificidade, observou-se não interferência dos excipientes. A precisão foi 100,76%. Os limites de detecção e de quantificação foram 0,057 e 0,172 µg.mL-1, respectivamente. Além disso, a validação do método demonstrou resultados satisfatórios para a precisão e robustez. O método proposto foi aplicado para a análise da incorporação do FLU em ME e cristais líquidos, contribuindo para aumentar o controle de qualidade e garantir a eficácia terapêutica.

Aspectos fundamentais no desenvolvimento de sistemas microemulsionados contendo anfotericina B para uso oftálmico / An overview of the development of microemulsion systems containing amphotericin B for ophthalmic use

A exemplo do que ocorre com outros fármacos, a biodisponibilidade da anfotericina B (AmB) através da via ocular repreesenta um grande desafio para a pesquisa científica. Na verdade, a baixa biodisponibilidade apresentada por tal molécula é devido, principalmente, a presença das barreiras oculares que impedem a absorção deste fármaco para os tecidos internos. A toxicidade associada a este fármaco, assim como a sua baixa capacidade em permear a córnea íntegra também consiste em um problema associado ao seu uso clínico. Novos veículos seguros e eficazes para a liberação ocular da AmB são, portanto, necessários. As microemulsões (MEs) aparecem como um interessante sistema devido à sua transparência, estabilidade termodinâmica e favorável viscosidade. O conhecimento do processo de formação das MEs contendo AmB, assim como a compreensão de toda a sua caracterização físico-química correspondem a aspectos importantes para se determinar as condições favoráveis para que estes sistemas venham a ser empregados como colírios. Esta revisão tem como objetivo, portanto, abordar este tema enfatizando os principais aspectos relacionados com a utilização de MEs como sistemas de liberação para a AmB através da via tópica oftálmica.

As occurs with a number of drugs, the bioavailability of amphotericin B (AmB) used to treat fungal infections by the ocular route remains a great challenge to research scientists. In fact, the poor bioavailability of AmB is due mainly to the corneal barrier, which leads to a precorneal loss and consequent decrease in the absorption of this drug into the intraocular tissues. The toxicity associated with this molecule, together with its poor ability to penetrate the intact corneal epithelium, also represents a major drawback to its clinical use. New effective and safe drug vehicles for ocular delivery of AmB are therefore urgently needed. Microemulsions (MEs) seem to be an interesting system, owing to their transparent appearance, thermodynamic stability and favorable viscosity. Knowledge of the process of formation of AmB-containing MEs, as well as a good understanding of the physical chemistry of such systems, would provide reliable information on the best conditions for the use of these systems as eye drops. The goal of this research was thus to make an approach to this subject by reviewing the main studies on the use of MEs as delivery systems for AmB in topical eye treatment.

Using Algebraic Geometry to Describe Boundaries of Microemulsion Regions in Nonionic Systems.

This study aimed to propose an empirical polynomial function based on algebraic geometry which could represent microemulsion regions in nonionic systems. The systems composed of olive oil (OO), water (W) and various ratios of sorbitan monooleate (SMO) and polyoxyethylene 20 sorbitan monooleate (PSMO) mixtures were investigated for their microemulsion regions obtained on the phase diagrams. Concept of algebraic geometry in this study was that description of close-boundary shape was cross-sectioning of a 3D-geometrical object with a plane which could be explained by an empirical polynomial function of the {oil, water, surfactant mixture}. In-house ad hoc software was created according to the proposed concept. It was found that this method could describe boundaries of microemulsion regions in the studied systems. Although this method could not reduce time consumption since it required intensive computational powers, the software could automatically run. Moreover, the developed program could provide acceptable level of accuracy.

Novel drug delivery systems in topical treatment of psoriasis: Rigors and vigors.

Psoriasis is a chronic inflammatory skin disorder that may drastically impair the quality of life of a patient. Among the various modes of treatments for psoriasis, topical therapy is most commonly used in majority of patients. The topical formulations based on conventional excipients could serve the purpose only to a limited extent. With the advent of newer biocompatible and biodegradable materials like phospholipids, and cutting-edge drug delivery technologies like liposomes, solid lipid nanoparticles (SLNs), microemulsions, and nanoemulsions, the possibility to improve the efficacy and safety of the topical products has increased manifold. Improved understanding of the dermal delivery aspects and that of designing and developing diverse carrier systems have brought in further novelty in this approach. Substantial efforts and the consequent publications, patents and product development studies on the subject are the matter of interest and review of this article. However, majority of the work is related to the preclinical studies and demands further clinical assessment in psoriasis patients.

Development and validation of HPLC method for analysis of dexamethasone acetate in microemulsions / Desenvolvimento e validação de método de HPLC para análise de acetato de dexametasona em microemulsões

A simple, rapid, accurate and sensitive method was developed for quantitative analysis of dexamethasone acetate in microemulsions using high performance liquid chromatography (HPLC) with UV detection. The chromatography parameters were stainless steel Lichrospher 100 RP-18 column (250 mm x 4 mm i.d., 5 μm particle size), at 30 ± 2 ºC. The isocratic mobile phase was methanol:water (65:35; v/v) at a flow rate of at 1.0 mL.min-1. The determinations were performed using UV-Vis detector set at 239 nm. Samples were prepared with methanol and the volume injected was 20 μL. The analytical curve was linear (r² 0.9995) over a wide concentration range (2.0-30.0 μg.mL-1). The presence of components of the microemulsion did not interfere in the results of the analysis. The method showed adequate precision, with a relative standard deviation (RSD) smaller than 3 percent. The accuracy was analyzed by adding a standard drug and good recovery values were obtained for all drug concentrations used. The HPLC method developed in this study showed specificity and selectivity with linearity in the working range and good precision and accuracy, making it very suitable for quantification of dexamethasone in microemulsions. The analytical procedure is reliable and offers advantages in terms of speed and low cost of reagents.

Um método simples, rápido, preciso e sensível foi desenvolvido para a análise quantitativa de acetato de dexametasona em microemulsões usando cromatografia líquida de alta eficiência (CLAE). Os parâmetros cromatográficos foram: coluna cromatográfica Lichrospher 100 RP-18, (250 mm x 4 mm i.d., 5 μm partícula tamanho), com temperatura de coluna de 30 ± 2 ºC. A fase móvel foi composta de metanol: água (65:35; v/v) com fluxo isocrático de 1 mL.min-1 e volume de injeção de 20 μL. As determinações foram realizadas utilizando detector UV-Vis no comprimento de onda de 239 nm. A curva analítica mostrou-se linear (r² 0,999) em uma ampla faixa de concentração (2,0-30,0 μg.mL-1). A presença de componentes da microemulsão não interferiu nos resultados da análise. O método mostrou precisão adequada, com desvio padrão relativo menor que 3 por cento. A exatidão foi analisada pela adição de padrões do fármaco e valores de recuperação dentro dos limites recomendáveis foram obtidos para todas as concentrações estudadas. O método por CLAE mostrou especificidade e seletividade com linearidade dentro da faixa de concentração utilizada e precisão e exatidão que tornam o método adequado para a análise de dexametasona em microemulsões. O procedimento analítico é fidedigno e oferece vantagens em termos de velocidade e custo de reativos.

Study on the Influence Factors for the Preparation of Reverse Microemulsions and the Optimization of Its Formula / 中国药房

OBJECTIVE:To study the effect of oil phase,emulsifier and drugs on reverse microemulsion.METHODS:Pseudo-ternary phase diagram was adopted to study the effect of Span-80/Tween-80(emulsifier),thymopentin(model drug), long-chain glyceride,medium-chain glyceride,non-glyceride(oil phase).on the preparation of reverse microemulsions.Optimal formula of reverse microemulsions was selected.RESULTS:The largest water-in-oil(W/O)area was obtained in reverse microemulsion which was prepared using medium-chain glyceride as oil phase.Final formula was confirmed and contained distilled water/ Span-80/Tween-80/caprylic/capric triglyceride(2∶3∶6∶9).In addition,thymopentin was incorporated into the aqueous phase.CONCLUSIONS:The preparation of reverse microemulsions will be influenced by emulsifier,constitution of oil phase and drug.The influence factors for the actual preparation of reverse microemulsions should be optimized.

Pharmacokinetics of diclofenac sodium microemulsions in rabbits / 第二军医大学学报

Objective: To study the pharmacokinetic progress of diclofenac sodium microemulsions in rabbits. Methods: Diclofenac sodium microemulsion and diclofenac sodium suspension were single orally given to rabbits. Diclofenac sodium concentrations in plasma were measured by HPLC method. Results: AUC 0 ∞ , c max1 and t max1 were 13.456 ?g?h?ml -1 , 2.852 ?g/ml and 1.438 h after po diclofenac sodium microemulsion and 10.584 ?g?h?ml -1 , 3.145 ?g/ml and 0.750 h after po diclofenac sodium suspension. Conclusion: The absorption of diclofenac sodium microemulsions in rabbits is slower and can keep a higher concentration in plasma for a long time compared with those of the suspension. [