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Objectives@#The stratum corneum (SC) remains an obstacle to the passage of drugs applied topically. Several investigations have focused on enhancing the penetration of drugs through the SC by integrating permeation enhancers (PE) into the drug formulation. Terpenes are among the PE utilized in formulations and are categorized by the regulatory bodies as generally recognized as safe (GRAS). This study aimed to comparatively analyze the skin permeation enhancing effect of terpenes on lipophilic drugs. @*Methods@#The present study reviewed the effects of terpenes on the permeation of lipophilic small-molecule drugs through the skin using original research published between 2000 - 2022 retrieved from PubMed®. The search phrase used was (lipophilic drug) AND (terpene) AND (permeation enhancer). @*Results@#Terpenes increase the percutaneous permeation of lipophilic small molecule drugs by 1.06 – 256.80-fold. Linear correlation analysis of terpenes’ cLog P with enhancement ratio (ER) revealed moderate and strong positive correlations in pig skin (r = 0.21) and mouse skin (r = 0.27), and rat skin (r = 0.41) and human skin (r = 0.67), respectively. Drug cLog P is a poor (r = -0.06) predictor of permeation enhancement. Terpenes with cLog P higher than 2.40 had ER greater than 10. Higher ERs (>30) were recorded for nerolidol, carvacrol, borneol, terpineol, limonene, menthone, pulegone, and menthol among the terpene-chemical penetration enhancers. @*Conclusion@#cLog P of terpene-based chemical permeation enhancers (CPE) is strongly correlated with ER of lipophilic drugs across human skin. Non-polar groups in terpenes and hydrogen bond interactions by terpenes with SC lipid enhance cutaneous drug penetration of lipophilic drugs.
Subject(s)
Terpenes , SkinABSTRACT
OBJECTIVE：To prepare supersaturated system of lip ophilic aci clovir（ACV）prodrug，and to increase the cutaneous bioavailability of ACV. METHODS ：Three prodrugs of ACV were synthesized by anhydride acylation ，i.e. aciclovir acetate （ACV-Ace），butyrate（ACV-But）and hexanoate （ACV-Hex）. The structures of ACV and three ACV prodrugs were confirmed by 1H-NMR and HRESI-MS ；the concentrations of ACV and three ACV prodrugs were determined by UPLC-triple quadrupole tandem mass spectrometry ，and saturated solubility of them in different volume fractions of propylene glycol-water solution was calculated. The compound with the greatest potential of form supersaturated system was screened out. The supersaturated system of that compound was prepared by co-solvent method. The effect of hydroxypropyl methylcellulose E 3 （HPMC E 3） on its physical stability was observed by light microscope. Vertical Franz diffusion cells were used to study the effects of degree of supersaturation （DS）and HPMC E 3 on the deposited amount of drug in the excised porcine skin after using the supersaturated system for 1 h. The distribution of ACV in the excised porcine skin was determined by frozen slicing stratified quantitative method after using the supersaturated system and marketed aciclovir cream for 1 h. RESULTS ：Three ACV prodrugs were successfully synthesized. The established quantification methods met the requirements of biological sample analysis. Among all of the three ACV prodrugs ， ACV-Hex showed the lowest saturated solubility in water [ （0.5±0.0）mmol/L] a nd the highest saturated solubility in propylene glycol [（53.4 ± 14.2）mmol/L]，which made it potentially feasible to form supersaturated system with high DS. In 10％propylene glycol-water system ，the addition of HPMC E 3 163.com enabled ACV-Hex supersaturated systems ，with DS no morethan 4，to maintain physical stability within 1 h. The total deposited amount （ACV + ACV-Hex ） in skin after the application of ACV-Hex supersaturated system with DS of 4 for 1 h was higher than that after the application of ACV-Hex supersaturated system with DS less than 4 or without HPMC E 3. In addition ，the concentration of ACV in the basal epidermis （skin thickness was 100-160 mm）by supersaturated system was significantly higher than that of the marketed aciclovir cream （P＜0.05）. CONCLUSIONS：ACV-Hex，the lipophilic prodrug of ACV ，can form stable supersaturated system with DS of 4 in 10％ propylene glycol-water system in the presence of HPMC E 3. High concentration of ACV could be accumulated in the basal epidermis after the skin was exposed to supersaturated system for 1 h，which may be valuable for local treatment skin infection of herpes simplex virus .
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Fingerprints of lipophilic components in the roots of Salvia miltiorrhiza and S.yunnanensis were analyzed by UPLC-DADand UPLC coupled with mass spectroscopy to evaluate the differences and similarities of the lipophilic components in the two kinds of herbs.The UPLC analysis of 18 batches of S.miltiorrhiza and 16 batches of S.yunnanensis was performed on a 25℃Thermo Accucore C_(18)column(2.1 mm×100 mm,2.6μm)by Shimadzu LC-20AD;mobile phase was 0.026%phosphoric acid(A)-acetonitrile(B)with gradient elution;flow rate was 0.4 m L·min~(-1);detection wavelength was set at 270 nm;injection volume was 2μL.The molecular structures of the lipophilic components were analyzed on a 25℃Thermo Accucore C_(18)column(2.1 mm×100 mm,2.6μm)by Thermo U3000 UPLC Q Exactive Orbitrap LC-MS/MS with a mobile phaseconsisting of 0.1%formic acid water(A)and 0.1%formic acidacetonitrile(B).The mass spectrometry was acquired in positive modes using ESI.There are 10 common peaks in the lipophilic components of S.miltiorrhiza.The similarity between the 16 batches of S.miltiorrhiza and their own reference spectra was greater than 0.942,and the average similarity was 0.973.There are 12 common peaks in the lipophilic components of S.yunnanensis.The similarity between the 18 batches of S.yunnanensis and their own reference spectra was greater than 0.937,and the average similarity was 0.976.The similarity between the reference chromatograms of S.miltiorrhiza and S.yunnanensis was only 0.900.There are three lipophilic components in S.yunnanensis,which are not found in S.miltiorrhiza,and one of which isα-lapachone.There is a lipophilic component in S.miltiorrhiza not found in S.yunnanensis,which may be miltirone.The two herbs contain 8 common lipophilic components including dihydrotanshinoneⅠ,cryptotanshinone,tanshinoneⅠ,tanshinoneⅡ_A,nortanshinone in which the content of tanshinoneⅡ_A,dihydrotanshinoneⅠand cryptotanshinone of S.yunnanensisis significantly lower than that of S.miltiorrhiza(P<0.01),and the contents of tanshinoneⅠand nortanshinone are significantly lower than that of S.miltiorrhiza too(P<0.05).There are significant differences in the types and contents of lipophilic components between the roots of S.miltiorrhiza and S.yunnanensis,and the similarity between the fingerprints of interspecies is much lower than that between the same species.Therefore,the roots of S.miltiorrhiza and S.yunnanensis are two kinds of herbs which are quite different in chemical compounds and compositions.
Subject(s)
Chromatography, Liquid , Abietanes , Molecular Structure , Plant Roots , Salvia miltiorrhiza , Tandem Mass SpectrometryABSTRACT
In view of the present situation that edible marine shellfishes are combinedly contaminated by different kinds of lipophilic toxins, common lipophilic shellfish toxins in marine shellfishes were simultaneously detected by liquid chromatography-tandem mass spectrometry, and the safety risk of commercial marine shellfish was evaluated using the risk assessment method based on combined contamination of various toxins. Under the optimum conditions, satisfactory recoveries (63. 3％ - 88. 8％ ), precision ( relative standard deviations RSD≤14. 5％ ) and sensitivity (limit of detection in the range of 0. 5-2. 7 ng / g) of the method were achieved for all the analytes. Among the 105 commercially available shellfish samples, 42. 86％ of the samples had at least a kind of toxin. The highest average content was 47. 6 μg / kg of DTX1, which was the most serious contaminant for marine shellfishes. The total Expose Risk Index (∑ERI) was calculated based on Tolerable Daily Intake (TDI) and Acute Reference Dose (ARfD) of each toxin to evaluate the safety risk of commercial marine shellfish. The results showed that the ratio of commercially available marine shellfish with safety risk was 19. 05％ and the food safety risk of scallop was the highest. In summary, a new method based on the combined contamination of lipophilic shellfish toxins was successfully developed for risk assessment of the commercial marine shellfish. The proposed method is more harsh compared with the European Food Safety Authority (EFSA) regulation and can make shellfish consumers better to avoid the risk of poisoning.
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Objective: To improve in vitro dissolution of lipophilic constituents in Compound Danshen Tablet, a novel freeze-dried emulsion was designed and developed. Methods: Compound Danshen liquid emulsion was prepared by high-speed shearing, following by high pressure homogenization process. The oil phase and cryoprotectants were optimized by uniform design test, using physical appearance and redispersibility as evaluation indexes. The in vitro dissolution profile of tanshinone IIA and borneol in the freeze-dried emulsion and Compound Danshen Tablet was determined in artificial gastric juice and artificial intestinal juice containing 0.5% sodium lauryl sulfate (SDS). Based on the appearance, average particle size and zeta potential, the stability of freeze-drying emulsion was investigated. Results: The developed Compound Danshen freeze-dried emulsion had good physical appearance, meanwhile maintained a good redispersibility and stability, when 10% medium chain triglycerides (MCT) was adopted as oil phase of liquid emulsion and 18% maltose combined with 0.25% beta-cyclodextrin was optimized as cryoprotectants. In artificial gastric juice, the accumulated dissolution rates of tanshinone IIA and borneol in Compound Danshen freeze-dried emulsion reached up to (94.8 ± 2.8)% and (97.4 ± 2.9)% at 30 min, respectively. However, the accumulated dissolution rate of borneol in the tablet was only (23.3 ± 3.4)% at 120 min, while tanshinone IIA showing no dissolution. In artificial intestinal juice, the accumulated dissolution rates of tanshinone IIA and borneol in the tablet rose to (42.5 ± 2.7)% and (74.4 ± 1.8)% at 120 min, but they were still much lower than that in the freeze-dried emulsion which reached up to (97.8 ± 1.9)% and (92.7 ± 3.5)%. After one year's storage, there were no significant changes of the stability evaluation index for freezing dry emulsion. Conclusion: The dissolution rates of lipophilic constituents in Compound Danshen freeze-dried emulsion increased significantly and exhibited a fast and fairly complete drug release, which provides a potential and promising formulation to improve bioavailability of the original dosage form of tablet. Its physical stability is good.
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In order to provide scientific basis for quality evaluation of Lepidium meyenii Walp.in Sichuan province,the extracted constituents of essential oil and petroleum ether were analyzed by gas chromatography-mass spectrometry (GC-MS),respectively.The volatile oil and fat soluble components were extracted by the steam distillation and petroleum ether ultrasonic.They were isolated and identified by GC-MS.The structures were identified in combination with database search system of MS.The relative content of every compound was determined by normalization method.The results showed that a total of 22 compounds were identified in volatile oil (98.85％) and 40 compounds were identified in liposoluble constituents (73.99％).There were significant differences of components and relative percentage contents of volatile oil and fat-soluble components.Dodecane,quinoline,3-methoxybenzaldehyde,palmitic acid methyl ester and ethyl linoleate were the same compositions.Comparative analysis was conducted on volatile oil and liposoluble constituents by GC-MS for the first time.The results provided references for herbal resource investigation and quality standard evaluation of Maca.
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Objective To determine hydrophilic–lipophilic balance (HLB) value, stability of formulate emulsion and properties of sacha inchi oil. Methods The physiochemical characteristics of sacha inchi oil were first investigated. Free radical scavenging property was studied by DPPH assay. HLB value of sacha inchi oil was experimentally determined by preparing the emulsion using emulsifiers at different HLB value. Sacha inchi oil emulsion was prepared using the obtained HLB and its stability was conducted by centrifugation, temperature cycling, and accelerated stability test. The efficiency of the prepared emulsion was clinically investigated by 15 volunteers. The primary skin irritation was performed using closed patch test. Subjective sensory assessment was evaluated by using 5-point hedonic scale method. Results Peroxide value of sacha inchi oil was 18.40 meq O
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Objective:To determine hydrophilic-lipophilic balance (HLB) value,stability of formulate emulsion and properties of sacha inchi oil.Methods:The physiochemical characteristics of sacha inchi oil were first investigated.Free radical scavenging property was studied by DPPH assay.HLB value of sacha inchi oil was experimentally determined by preparing the emulsion using emulsifiers at different HLB value.Sacha inchi oil emulsion was prepared using the obtained HLB and its stability was conducted by centrifugation,temperature cycling,and accelerated stability test.The efficiency of the prepared emulsion was clinically investigated by 15 volunteers.The primary skin irritation was performed using closed patch test.Subjective sensory assessment was evaluated by using 5-point hedonic scale method.Results:Peroxide value of sacha inchi oil was 18.40 meq O2/kg oil and acid value was 1.86 KOH/g oil.The major fatty acids are omega-3 (44％),omega-6 (35％) and omega-9 (9％).The vitamin E content was 226 mg/100 g oil.Moreover,sacha inchi oil (167 ppm)and its emulsion showed 85％ and 89％ DPPH inhibition,respectively.The experimental HLB value of sacha inchi oil was 8.5.The sacha inchi oil emulsion exhibited good stability after stability test.The emulsion was classified as non-irritant after tested by primary skin irritation method.The skin hydration value significantly increased from 38.59 to 45.21 (P ＜ 0.05) after applying sacha inchi oil emulsion for 1 month and the overall product satisfaction of volunteers after use was with score of 4.2.Conclusions:This work provides information on HLB value and emulsion properties of sacha inchi oil which is useful for cosmetic and pharmaceutical application.
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ABSTRACT Formulators face great challenges in adopting systematic approaches for designing self-nanoemulsifying formulations (SNEFs) for different drug categories. In this study, we aimed to build-up an advanced SNEF development framework for weakly basic lipophilic drugs, such as cinnarizine (CN). First, the influence of formulation acidification on CN solubility was investigated. Second, formulation self-emulsification in media with different pH was assessed. Experimentally designed phase diagrams were also utilized for advanced optimization of CN-SNEF. Finally, the optimized formulation was examined using cross polarizing light microscopy for the presence of liquid crystals. CN solubility was significantly enhanced upon external and internal acidification. Among the various fatty acids, oleic acid-based formulations showed superior self-emulsification in all the tested media. Surprisingly, formulation turbidity and droplet size significantly decreased upon equilibration with CN. The design was validated using oleic acid/Imwitor308/Cremophor El (25/25/50), which showed excellent self-nanoemulsification, 43-nm droplet size (for CN-equilibrated formulations), and 88 mg/g CN solubility. In contrast to CN-free formulations, CN-loaded SNEF presented lamellar liquid crystals upon 50% aqueous dilution. These findings confirmed that CN-SNEF efficiency was greatly enhanced upon drug incorporation. The adopted strategy offers fast and accurate development of SNEFs and could be extrapolated for other weakly basic lipophilic drugs.
Subject(s)
Solubility/drug effects , Process Optimization/classification , Cinnarizine/analysis , Drug Compounding/statistics & numerical data , Acidification/analysisABSTRACT
Cardiovascular drugs are commonly used in clinical medicine,which can cause refractory shock and cardiac arrest when poisoning.Lipid emulsion was mainly used for detoxification of lipophilic anesthetics poisoning in the past.Recently more and more studies and clinical cases suggest that lipid emulsion can be adopted as one of therapies for cardiovascular drugs poisoning.Now we review and focus on the research status of the lipid emulsion in the treatment of cardiovascular drugs poisoning,the related mechanisms of detoxification,therapeutic regimen and adverse effect.
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The particles suspended in seawater have great influence on pollutant migration and transformation in marine environment, while the lipophilic algae toxins enriched by the particles suspended in seawater will lead more serious toxicity to marine filter feeders. In this study, a new method was developed for the simultaneous determination of eight lipophilic algae toxins in suspended particles by ultra performance liquid chromatography-tandem mass spectrometry ( UPLC-MS/MS ) . After extracted with methanol by ultrasonic-assisted extraction, the sample was separated on an Acquity UPLC BEH C18 column (50 mm×2. 1 mm, 1. 7 μm) using gradient elution of acetonitrile and water containing 5 mmol/L ammonium acetate as eluent modifiers. The qualitative and quantitative analyses were carried out by electrospray ionization ( ESI) tandem mass spectrometry in multiple reaction monitoring ( MRM) mode. Under the optimal conditions, satisfactory precision (relative standard deviations (RSD≤14. 1%), recoveries (83. 8%-110. 4%) and detection limits (2. 9-103 pg/g) of the method were achieved. Good linearity (R2≥0. 99) was also obtained for all studied analytes. Then, the method was applied to determine the amounts of the eight lipophilic marine toxins in authentic suspended particle samples collected from Qingdao near-shore area. Pectenotoxin 2 ( PTX2 ) was detected in the samples from Shilaoren beach and No. 3 bathing beach with concentration ranges of 717 and 790 pg/g, respectively.
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@#Ten compounds were isolated from the 95% ethanol extract of the stem bark of Toona sinensis by silica gel, ODS Sephadex LH-20 column chromatographies and preparation TLC methods. Their structures were elucidated by spectroscopic methods and chemical properties as betulinic acid(1), stigmastane-3, 6-dione(2), stigmast-4-en-3-one(3), 7β-hydroxysitosterol(4), 6-hydroxystigmast-4-en-3-one(5), stigmast-4-ene-3β, 6β-diol(6), ergosterol peroxide(7), 7-methoxy-2-(3, 4-methylenedioxyphenyl)benzofuran-5-carboxylate(8), canthin-6-one(9), and α-acetylamino-phenylpropyl α-benzoylamino phenylpropionate(10). All compounds were isolated from T. sinensis for the first time.
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Over past twenty years a large number of ligands, both agonists and antagonists have been developed by computational methodologies which are used to increase the efficiency of drug discovery process by rendering the design of new drug candidates. Both 2D and 3D-quantitative structure activity relation (QSAR) studies have been carried out using topological parameters along with thermodynamic and structural descriptors. The scope of this review is to highlight the use of pharmacophoric models and QSAR studies for identification and optimization of new ligands having potential to develop as drug candidates.
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El género Malassezia comprende un grupo de levaduras lipofílicas que forman parte de la microbiota de la piel del hombre y otros vertebrados. Sin embargo se han relacionado con varias entidades dermatológicas. En esta investigación se planteó como objetivo caracterizar las especies de Malassezia aisladas en piel sana de estudiantes del Liceo Baralt de la Ciudad de Maracaibo- Edo. Zulia. Las muestras fueron tomadas, mediante el método de la impronta con cinta adhesiva transparente, de cuero cabelludo, pabellón auricular, pecho y espalda e inoculadas en el medio Dixon Agar modificado e incubadas a 32°C por 14 días. La identificación de las especies se realizó siguiendo las claves descritas por Gueho y Cols. y el test de difusión en tween propuesto por Guillot y Cols, la prueba de la catalasa y la utilización de triptófano como única fuente de carbono. De un total de 100 estudiantes evaluados 81(81%) fueron positivos a Malassezia, se obtuvo 184 aislamientos, 100 (54,30%) para el sexo masculino y 84 (45,6%) para el femenino. Los resultados muestran una alta prevalencia de Malassezia furfur (54,3%) seguida de Malassezia sympodialis (45,1%) y Malassezia globosa (0,50%). Las localizaciones anatómicas con mayor número de aislamientos fueron espalda (33%) y pecho (30,2%).
The genus Malassezia includes a group of lipophilic yeasts that form part of the microbiota of the skin of humans and other vertebrates. Nevertheless, they have been related to several dermatological entities. This research proposed to characterize the morfo-physiological Malassezia species isolated on the healthy skin of students at the Baralt High School in the city of Maracaibo, State of Zulia. Samples were taken using the imprint method with adhesive transparent tape on the scalp, pinna, chest and back, inoculated into a modified Dixon Agar medium and incubated at 32°C for 14 days. Identification of the species was carried out following the keys described by Gueho and Cols, the diffusion in tween test proposed by Guillot and collaborators, the catalase test and the utilization of triptophan as the only source of carbon. Out of a total of 100 evaluated students, 81 (81%) were positive for Malassezia and 184 isolations were obtained; 100 (54.30%) were of the masculine sex and 81 (45.6%) were females. The results show a high prevalence of Malassezia furfur (54.3%) followed by Malassezia sympodialis (45.1%) and finally, Malassezia globosa (0.50%). Anatomical locations with the greatest number of isolations were the back (33%) and chest (30.2%).
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Background Enteric red mouth disease and Saprolegniasis, which are caused by the bacteria Yersinia ruckeri and the oomycete Saprolegnia parasitica, respectively, are important illnesses that affect salmonid farming. Sanitary problems in farms are addressed by the prevention of disease outbreaks or by the treatment of diseases with chemicals. Environmental and governmental restrictions, toxicity and high treatment costs limit the use of drugs. Marine organisms, such as algae, sponges and corals, have developed an antimicrobial defense strategy based on the production of bioactive metabolites. Among these organisms, seaweeds offer a particularly rich source of potential new drugs. Hence, many pharmacologically active substances have been isolated from seaweeds. In the Ceramium genus, Ceramium rubrum has been emphasized by several authors for its antimicrobial properties. Based on this background, the present study focused on the antimicrobial activity of a lipophilic extract of C. rubrum on Y. ruckeri and S. parasitica. Results The alga, collected from the Pacific coast of Chile, underwent an ethanol extraction, and the concentrated extract was partitioned between water and dichloromethane. From the dichloromethane extract, fatty acids, fatty acid esters, one hydrocarbon and phytol were identified by Gas Chromatography-Mass Spectrometry (GC/MS) analysis. The antimicrobial study showed that the whole extract was more active than the individual components, which suggests a strong synergistic effect among the components. Conclusions These results may constitute a basis for promising future applied research that could investigate the use of C. rubrum seaweed as a source of antimicrobial compounds against fish pathogens.
Subject(s)
Animals , Plant Extracts/pharmacology , Saprolegnia/drug effects , Yersinia ruckeri/drug effects , Rhodophyta/chemistry , Fish Diseases , Methylene Chloride/pharmacology , Anti-Infective Agents/pharmacology , Salmonidae , Seaweed , Colony Count, Microbial , Gas Chromatography-Mass SpectrometryABSTRACT
Objective: To study the chemical constituents of lipophilic parts from the roots of Angelica dahurica. Methods: The compounds were separated and purified by repeated column chromatography on silica gel and HPLC, as well as the chemical structures of isolated compounds were determined by spectral data analyses. Results: Forty compounds were obtained and identified as isoimperatorin (1), psoralen (2), bergapten (3), β-sitosterol (4), imperatorin (5), phellopterin (6), xanthotoxin (7), isopimpinellin (8), dehydrogeijerin (9), isooxypeucedanin (10), oxypeucedanin (11), dibutylphthalate (12), umbelliferone (13), xanthotoxol (14), 5-hydroxy-8-methoxypsoralen (15), p-hydroxyphenethyl-trans-ferulate (16), pabularinone (17), isobyakangelicol (18), heraclenin (19), columbianetin (20), isogosferol (21), pabulenol (22), byakangelicin ethoxide (23), neobyakangelicol (24), oxypeucedanin methanolate (25), isoscopletin (26), 1′, 2′-dehydromarmesin (27), angelol A (28), angelol E (29), tert-O-methylheraclenol (30), (-)-marmesin (31), dahurianol {8-[(2′R)-2′, 3′-dihydroxy-3′-methylbutoxy] bergaptol; 32}, oxypeucedanin hydrate (33), heraclenol (34), byakangelicin (35), angelol L (36), angelol G (37), trans-coniferylaldehyde (38), vanillic acid (39), and trans-ferulic acid (40), respectively. Conclusion: Compound 32 is a new natural product named dahurianol.
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La ciclosporina A (CsA) por sus propiedades inmunosupresoras es empleada en el transplante de órganos sólidos, médula ósea, así como para determinados estadíos de ciertas enfermedades autoinmunes. En Cuba, se comercializa una solución oral que presenta problemas de absorción gastrointestinal. Objetivos: lograr una microemulsión preconcentrada conteniendo ciclosporina A con alto grado de dispersión, igual o mayor que la formulación comercial. Métodos: se realizó un estudio de porcentajes de los emulgentes y el balance hidrófilo lipófilo (HLB), en los intervalos que permitieran obtener sistemas automicroemulsionables a través de un diseño factorial multinivel. Se empleó el porciento de transmitancia como variable de respuesta en la determinación del grado de dispersión de la formulación. También se realizó la evaluación de las características organolépticas de la formulación seleccionada, el estudio reológico, el conteo microbiano y la efectividad antimicrobiana. Resultados: los factores estudiados tienen influencia significativa sobre el porcentaje de transmitancia, la formulación con mayor grado de dispersión se logró empleando un 60 por ciento de emulgentes junto a un HLB de 11,5 con valores de transmitancia de 95,03 por ciento, significativamente mayor que el del producto líder en formato de cápsulas blandas que fue de 84,6 por ciento. Organolépticamente el producto cumple con las características de líquido transparente, brillante y sin partículas en suspensión, con comportamiento Newtoniano desde el punto de vista reológico. El conteo de bacterias y hongos cumplió con los requisitos establecidos en la Farmacopea de los Estados Unidos para soluciones orales. Conclusiones: se logró una microemulsión preconcentrada de CsA en solución bebible con alto grado de dispersión, cumpliendo con los requisitos físicos y microbiológicos establecidos para este tipo de forma farmacéutica
Cyclosporine A (CsA), due to its immunosuppressive properties, is used in the transplantation of solid organs, bone marrow, and in some stages of certain autoimmune diseases. In Cuba, the Cyclosporine A oral solution causes gastrointestinal absorption problems. Objectives: to achieve a pre-concentrated micro-emulsion containing highly dispersed cyclosporine A that may be equal to or higher than the one in the commercial formulation. Methods: study of percentages of emulsifiers and of hydrophilic lipophilic balance (HLB), at some intervals that allow obtaining self-emulsifying systems through a multilevel factorial design. The percent transmittance was used as the response variable in determining the formulation dispersion degree. The evaluation of the organoleptic characteristics of the selected formulation, the rheological study, the microbial count and the antimicrobial effectiveness estimation were all performed. Results: the studied factors have a significant influence on the transmittance percentage, the formulation with the highest degree of dispersion was achieved when using 60 percent of emulsifiers and an HLB of 11.5, being transmittance values of 95.03 percent, which were significantly higher than those of the leading product in the form of soft capsules, equal to 84.6 percent. Organoleptically speaking, the product meets the characteristics of a clear brilliant fluid without suspended particles and Newtonian behavior from the rheological point of view. The bacteria and fungi count met requirements of U.S. Pharmacopoeia for oral solutions. Conclusions: a pre-concentrate highly dispersed CsA microemulsion was achieved in a drinkable solution meeting the physical requirements and microbiological criteria established for this type of dosage form
Subject(s)
Cyclosporine/pharmacology , Emulsions , Immunosuppressive AgentsABSTRACT
Bryophytes are known to produce a great range of biologically active compounds viz. terpenoids, aromatic compounds, and acetogenins. A lot of these constituents have typical odour, tanginess, and bitterness, and exhibit a fairly curious collection of bioactivities and medicinal properties. Chemical studies of the bryophytes were neglected for a long time in India. They are stockroom of naturally occurring materials. Many of these materials display substantial biological activity. Investigations are hindered commonly because of too little amounts of plant material. The resulting low yields of components are then generally insufficient to allow testing for biological activity. In vitro culture and suitable chemical synthesis on a preparative scale are now being undertaken to overcome this difficulty. In present review the bryophytes of Indian territory and their biologically active compounds have been highlighted which need to be used in sustainable manner.
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The purpose of the present work was to investigate synaptic vesicle trafficking when vesicles exhibit alterations in filling and acidification in two different synapses: a cholinergic frog neuromuscular junction and a glutamatergic ribbon-type nerve terminal in the retina. These synapses display remarkable structural and functional differences, and the mechanisms regulating synaptic vesicle cycling might also differ between them. The lipophilic styryl dye FM1-43 was used to monitor vesicle trafficking. Both preparations were exposed to pharmacological agents that collapse ΔpH (NH4Cl and methylamine) or the whole ΔµH+ (bafilomycin), a necessary situation to provide the driving force for neurotransmitter accumulation into synaptic vesicles. The results showed that FM1-43 loading and unloading in neuromuscular junctions did not differ statistically between control and experimental conditions (P > 0.05). Also, FM1-43 labeling in bipolar cell terminals proved highly similar under all conditions tested. Despite remarkable differences in both experimental models, the present findings show that acidification and filling are not required for normal vesicle trafficking in either synapse.
O objetivo do presente trabalho foi investigar o tráfego de vesículas sinápticas quando estas apresentam alterações no armazenamento de neurotransmissores e acidificação em duas distintas sinapses: a junção neuromuscular colinérgica de rãs versus o terminal nervoso glutamatérgico do tipo ribbon em céulas bipolares da retina. Essas sinapses exibem notáveis diferenças estruturais e funcionais e os mecanismos de regulação de ciclo das vesículas sinápticas podem ser diferentes entre eles. Para monitorar o tráfego de vesícula, foi utilizado o marcador lipofílico FM1-43. Ambas as preparações foram expostas a agentes farmacológicos que provocam o colapso de ΔpH (NH4Cl e metilamina) ou de todo ΔµH+ (bafilomicina), gradientes necessários para o acúmulo de neurotransmissores em vesículas sinápticas. Nossos resultados demonstram que a marcação e desmarcação de FM1-43 nas junções neuromusculares não foi estatisticamente diferente entre as diversas condições experimentais (P > 0,05). Além disso, a marcação de FM1-43 em terminais sinápticos de células bipolares foram bastante semelhantes em todas as condições testadas. Apesar das diferenças marcantes em ambos os modelos experimentais, nossos achados demonstram que a acidificação e o preenchimento de vesículas sinápticas não são necessários para o tráfico normal da vesícula nas sinapses estudadas.
Subject(s)
Synapses/metabolism , Synaptic Vesicles/classification , Acidification/analysis , Retinal Bipolar Cells/classificationABSTRACT
Agaricoglyceride A (AGA), showed strong activities against neurolysin. The objectives of this study was to prepare solid self-emulsifying drug delivery system (sSEDDS) by spray drying the SEDDS (liquid system) using Aerosil 200 as the inert solid carrier, and to evaluate the enhanced bioavailability (BA) of AGA from sSEDDS. The AGA formulated in the sSEDDS was quickly and completely dissolved within 20min, both in 0.1N HCl and phosphate buffer pH 6.8 dissolution media, whereas AGA powder was significantly less dissoluble. Meanwhile, the sSEDDS formulation was stable for at least 90days at room temperature. the plasma levels of AGA in the solid SEDDS group at the dose level (15mg/kg) remained detectable for up to 1.5 h after the oral dose. After oral administration to rats, a significant increase (P<0.0001) in the Cpmax and AUC0→24 h were observed in the sSEDDS group when compared with the AGA powder group. Furthermore, AGA-loaded sSEDDS exerted significant antinociceptive properties and alleviated pain insults in mice. The results suggest that the sSEDDS could be considered and further evaluated for the oral delivery of lipophilic poorly soluble drugs for which an oral route of administration is desirable.