Showing papers in "Die Pharmazie in 2001"
Journal Article•
TL;DR: Results indicate that TTO and EUO affect the virus before or during adsorption, but not after penetration into the host cell, suggesting their possible application as antiviral agents in recurrent herpes infection is promising.
Abstract: The antiviral effect of Australian tea tree oil (TTO) and eucalyptus oil (EUO) against herpes simplex virus was examined. Cytotoxicity of TTO and EUO was evaluated in a standard neutral red dye uptake assay. Toxicity of TTO and EUO was moderate for RC-37 cells and approached 50% (TC50) at concentrations of 0.006% and 0.03%, respectively. Antiviral activity of TTO and EUO against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) was tested in vitro on RC-37 cells using a plaque reduction assay. The 50% inhibitory concentration (IC50) of TTO for herpes simplex virus plaque formation was 0.0009% and 0.0008% and the IC50 of EUO was determined at 0.009% and 0.008% for HSV-1 and HSV-2, respectively. Australian tea tree oil exhibited high levels of virucidal activity against HSV-1 and HSV-2 in viral suspension tests. At noncytotoxic concentrations of TTO plaque formation was reduced by 98.2% and 93.0% for HSV-1 and HSV-2, respectively. Noncytotoxic concentrations of EUO reduced virus titers by 57.9% for HSV-1 and 75.4% for HSV-2. Virus titers were reduced significantly with TTO, whereas EUO exhibited distinct but less antiviral activity. In order to determine the mode of antiviral action of both essential oils, either cells were pretreated before viral infection or viruses were incubated with TTO or EUO before infection, during adsorption or after penetration into the host cells. Plaque formation was clearly reduced, when herpes simplex virus was pretreated with the essential oils prior to adsorption. These results indicate that TTO and EUO affect the virus before or during adsorption, but not after penetration into the host cell. Thus TTO and EUO are capable to exert a direct antiviral effect on HSV. Although the active antiherpes components of Australian tea tree and eucalyptus oil are not yet known, their possible application as antiviral agents in recurrent herpes infection is promising.
269 citations
Journal Article•
TL;DR: Because of the specific role of neutrophil elastase in the inflammatory process its inhibition by phenolic natural compounds might be one explanation for the use of medicinal plants containing phenolic compounds in the treatment of inflammation.
Abstract: The influence of 40 phenolic compounds from plants were tested on the enzymatic activity of neutrophil elastase (EC 3.4.21.37). Among the flavonoids especially the compounds with a catecholic structure showed a strong inhibitory activity in the range of mumol/l, hyperosid was the strongest inhibitor with an IC50 of about 0.3 mumol/l. Lipophilic caffeic acid esters and phenolic compounds with catecholic structure elements in general inhibited the enzyme. Because of the specific role of neutrophil elastase in the inflammatory process its inhibition by phenolic natural compounds might be one explanation for the use of medicinal plants containing phenolic compounds in the treatment of inflammation.
99 citations
Journal Article•
TL;DR: The results showed that the ethylacetate honey extract showed antibacterial, anticandida and antifungal effects at low concentration and the release of honey extract from different ointment bases was depending on the constituents of the base, and its stability was found to be temperature and base dependent.
Abstract: Old and recent reports show that honey has beneficial effects on the skin as antiseptic for wounds, burns and ulcers and as a healing promoter. Many investigators confirmed the usefulness of honey in the treatment of skin infections as well as internal diseases. The factors behind these effects are not completely explained. The aim of this study is: a) to investigate the antimicrobial activity of crude honey, b) to separate the fractions responsible for its activity, c) to formulate the honey extract as semisolid dosage forms, d) to study its release, and e) to determine its stability. The results showed that the ethylacetate honey extract showed antibacterial, anticandida and antifungal effects at low concentration. The release of honey extract from different ointment bases was depending on the constituents of the base, and its stability was found to be temperature and base dependent.
83 citations
Journal Article•
TL;DR: Scoparinol, a diterpene, isolated from Scoparia dulcis showed significant analgesic and anti-inflammatory activity and sedative action in animals by a marked potentiation of pentobarbital-induced sedation.
Abstract: Scoparinol, a diterpene, isolated from Scoparia dulcis showed significant analgesic (p < 0.001) and anti-inflammatory activity (p < 0.01) in animals. A sedative action of scoparinol was demonstrated by a marked potentiation of pentobarbital-induced sedation with a significant effect on both onset and duration of sleep (p < 0.05). Measurement of urine volume after administration of scoparinol indicated its significant diuretic action.
77 citations
Journal Article•
TL;DR: Significant anti-HIV and anticancer activities were observed in vitro for some members of the series, compounds 1e, 4E, 4f, 5, 6 and 16 showing a significant activity in Leukemia, Lung, Breast and CNS anticancer evaluation.
Abstract: Some new fused heterobicyclic nitrogen systems such as 1,2,4-triazino[3,4-b] [1,3,4] thiadiazolones/thiadiazinones 4-15 and the related compounds 16-21 have been synthesized from treatment of 4-amino-3-mercapto-6-substituted-1,2,4-triazin-5-ones 1 with bifunctional oxygen and halogen compounds via heterocyclization reactions. Structures of the products have been deduced from their elemental analysis and spectral data. Significant anti-HIV and anticancer activities were observed in vitro for some members of the series, compounds 1e, 4e, 4f, 5, 6 and 16 showing a significant activity in Leukemia, Lung, Breast and CNS anticancer evaluation.
57 citations
Journal Article•
TL;DR: The nasal formulation of midazolam approaches the intravenous form in speed of absorption, serum concentration and clinical sedation effect, and no serious side effects were observed.
Abstract: Intranasal administration of midazolam has been of particular interest because of the rapid and reliable onset of action, predictable effects, and avoidance of injections. The available intravenous formulation (Dormicum i.v. solution from Hoffmann-La Roche) is however less than optimal for intranasal administration due to low midazolam concentration and acidity of the formulation (pH 3.0-3.3). In this study midazolam was formulated in aqueous sulfobutylether-beta-cyclodextrin buffer solution. The nasal spray was tested in 12 healthy volunteers and compared to intravenous midazolam in an open crossover trial. Clinical sedation effects, irritation, and serum drug levels were monitored. The absolute bioavailability of midazolam in the nasal formulation was determined to be 64 +/- 19% (mean +/- standard deviation). The peak serum concentration from nasal application, 42 +/- 11 ng ml-1, was reached within 10-15 min following administration and clinical sedative effects were observed within 5 to 10 min and lasted for about 40 min. Intravenous administration gave clinical sedative effects within 3 to 4 min, which lasted for about 35 minutes. Mild to moderate, transient irritation of nasal and pharyngeal mucosa was reported. The nasal formulation approaches the intravenous form in speed of absorption, serum concentration and clinical sedation effect. No serious side effects were observed.
54 citations
Journal Article•
TL;DR: The aims of the present study were to prepare spray-dried polymeric nanocapsules (NC) and nanospheres (NS) from poly(epsilon-caprolactone) (P epsilon C) suspensions containing diclofenac (DIC) and to determine the physicochemical properties of the formulations.
Abstract: The aims of the present study were to prepare spray-dried polymeric nanocapsules (NC) and nanospheres (NS) from poly(epsilon-caprolactone) (P epsilon C) suspensions containing diclofenac (DIC) and to determine the physicochemical properties of the formulations. NC or NS suspensions were prepared by interfacial deposition of the polymer. DSC-thermograms of raw materials and NC or NS suspensions (evaporated or spray-dried) were obtained using a PL-DSC. Spray-dried powders were prepared by addition of 3% (w/v) Aerosil 200 into suspensions of NC or NS. These mixtures were fed into a spray-dryer. DIC was assayed by HPLC. NC and NS spray-dried powders were examined under SEM (Jeol Scanning Microscope, JSM-5800). NC and NS suspensions had acceptable diameter, 340 and 247 nm respectively. The yields of NC and NS spray-dried powders were 80% and 75% and the recovery of the DIC was 99% and 93%, respectively. The melting peak of P epsilon C in NC and NS was observed at a temperature about 10 degrees C lower than in the raw material. In the NC thermograms the maximum of the oil (Miglyol 810) melting peak (+1.6 degrees C) was lowered about 7 degrees C. For spray-dried NC formulations, the SEM analyses of powders showed spherical microparticles of silicon dioxide, covered by nanoparticles (300 nm), while for spray-dried NS formulations the microparticles presented a rugged surface at the same magnification.
52 citations
Journal Article•
TL;DR: In vivo studies indicated significantly improved bioavailability of Pz from Ms with sustained and controlled blood level profiles as compared to i.v., oral and nasal administration of drug solution.
Abstract: Bioadhesive chitosan microspheres (Ms) of pentazocine (Pz) for intranasal systemic delivery were prepared with the aim of avoiding the first pass effect, and thus improving the bioavailability and achieving sustained and controlled blood level profiles, as an alternative therapy to injection and to obtain improved therapeutic efficacy in the treatment of chronic pain such as cancer, trauma and post-operative pain, etc. The formulation variables were drug loading, polymer concentration, stirring rate during crosslinking and oils. The microspheres (Ms) were subjected to evaluation for physical characteristics, such as particle size, incorporation efficiency, swelling ability, in vitro bioadhesion, in vitro drug release characteristics and in vivo performance in rabbits. Application of in vitro data to various kinetic equations indicated matrix diffusion controlled drug delivery from chitosan Ms. Drug loading, polymer concentration and stirring speed influenced the drug release profiles significantly while oils had negligible effect. In vivo studies indicated significantly improved bioavailability of Pz from Ms with sustained and controlled blood level profiles as compared to i.v., oral and nasal administration of drug solution. Good correlation was observed between in vitro and in vivo data.
52 citations
Journal Article•
TL;DR: Press-coated, time-controlled release tablets containing pseudoephedrine hydrochloride as a model drug have been formulated and the suitability of this highly soluble drug in relation to the new drug delivery system was evaluated.
Abstract: In chronopharmacotherapy, circadian changes in disease symptoms are taken into account. Press-coated, time-controlled release tablets containing pseudoephedrine hydrochloride as a model drug have been formulated and the suitability of this highly soluble drug in relation to the new drug delivery system was evaluated. Hydroxypropylmethylcellulose was used in the coat of the tablet to adjust drug release. If such a formulation was administered in the evening it would have maximal effect in the early morning, and would be useful for the treatment of nocturnal symptoms. Two cross-over, single-dose bioavailability studies were carried out on eight healthy volunteers. A dissolution test method was developed to establish level A and level C in vitro/in vivo correlation for four formulations. With a low viscosity grade of polymer, peak concentrations were achieved after five hours. The drug was absorbed much more slowly from tablets containing a high viscosity grade polymer, with a plasma peak at ten hours. For further development of the drug delivery system described, a dissolution test method at pH 7.2 at a rotation speed of 150 min-1 is recommended on the basis of level A in vitro/in vivo correlation.
44 citations
Journal Article•
TL;DR: In this article, the authors present pharmaceutical relevant literature of the last twenty years with special emphasis on extraction of natural materials, including the extraction of vegetable oils from plant material in analytical and preparative scale, the preparation of essential oils for food and cosmetic industry and the isolation of substances of pharmaceutical relevance.
Abstract: The appearance of a supercritical state was already observed at the beginning of the 19th century. Nevertheless, the industrial extraction of plant and other natural materials started about twenty years ago with the decaffeination of coffee. Today carbon dioxide is the most common gas for supercritical fluid extraction in food and pharmaceutical industry. Since pure supercritical carbon dioxide is a lipophilic solvent, mixtures with organic solvents, especially alcohols, are used to increase the polarity of the extraction fluid; more polar compounds can be extracted in this way. The main fields of interest are the extraction of vegetable oils from plant material in analytical and preparative scale, the preparation of essential oils for food and cosmetic industry and the isolation of substances of pharmaceutical relevance. Progress in research was made by the precise measurement of phase equilibria data by means of different methods. Apart from extraction, supercritical fluid chromatography was introduced in the field of analytics, as well as micro- and nanoparticle formation using supercritical fluids as solvent or antisolvent. This review presents pharmaceutical relevant literature of the last twenty years with special emphasis on extraction of natural materials.
43 citations
Journal Article•
TL;DR: The aim of the study was to investigate melt granulation in a laboratory scale fluid-bed granulator with respect to granule growth, granule properties and resulting tablet properties.
Abstract: The aim of the study was to investigate melt granulation in a laboratory scale fluid-bed granulator with respect to granule growth, granule properties and resulting tablet properties. The parameters investigated were method of addition of PEG (spray-on or addition as flakes), binder concentration, PEG type (3000, 4000 and 6000, sprayed-on), size (PEG 4000, added as three different sized flakes), powder type (two different sized lactose types and corn starch) and operating conditions (volume air flow and heating temperature). Addition of binder as flakes led to layering as a growth mechanism when the size of the flakes was high. Coalescence occurred when the size was low. Coalescence also occurred when spraying was the method of addition. Due to the greater viscosity of the PEG 6000 melt it produced bigger granules than 3000 or 4000. The influence of volume air flow was moderate and the influence of heating temperature in the range of 70-90 degrees C was very low with both methods of addition. The disintegration time of tablets from granules where PEG was added as flakes was shorter than from granules where PEG was sprayed-on. The latter method of binder addition led to tablets which did not disintegrate but eroded. This was apparently caused by formation of a binder matrix, which could not be destroyed by the disintegrant.
Journal Article•
TL;DR: Observations suggest that liposomes coated with lectin (Con-A) were able to maintain the sugar affinity and specificity of the associated ligand and could be targeted to the surface 'glyco-calyx' of bacterial bio-film.
Abstract: Liposomes constructed of egg phosphatidylcholine (EPC), cholesterol (Chol) and stearoylamine (SA) were coated with lectin (Concanavalin-A). These lectinized liposomes were found to retain the ligand binding activity of surface coated concanavalin A (Con-A) as demonstrated by bovine submaxillary mucin (BSM) binding assay. Moreover the ligand specificity of Con-A was maintained even after coating the liposome surface because the presence of competing sugar alpha-methyl mannoside, significantly inhibited the interaction of lectinized liposomes and BSM. The significance of divalent cations for these interactions was studied. The Con-A coating was found to be stable in simulated salivary fluids (SSF, pH 7.2) and under various pH conditions. In vitro targeting studies of lectinized liposomes with gram-negative bacilli (Streptococcus mutans) that harbor in the periodontal pocket (biofilm) demonstrated nearly 100% bacterial growth inhibition (% BGI). The antimicrobial effect was maintained for 360 min. The results were compared with metronidazole bearing plain (protein free/uncoated) liposomes and the free drug at the same dose levels. Mechanisms involved are also discussed. These observations suggest that liposomes coated with lectin (Con-A) were able to maintain the sugar affinity and specificity of the associated ligand and could be targeted to the surface 'glyco-calyx' of bacterial bio-film.
Journal Article•
TL;DR: Measurements of the ciliary beat frequency of human ciliated nasal epithelium showed that LPC resulted in total loss of ciliated cells while DM beta CD, TMC and chitosan hydrochloride did not cause any major changes in CBF.
Abstract: The intranasal toxicity of selected absorption enhancers (LPC, DM beta CD, N-trimethyl chitosan chloride (TMC) and chitosan hydrochloride) were determined in vivo by investigating the acute microscopic toxic potential on the morphology of rat nasal epithelium with transmission electron microscopy (TEM) and in vitro by measurement of the ciliary beat frequency (CBF), of human ciliated nasal epithelium. TEM evaluations showed that LPC (1% w/v) caused severe epithelial damage and pyknosis. No damage to the rat nasal epithelium was caused by the other absorption enhancers. CBF measurements showed that LPC resulted in total loss of ciliated cells while DM beta CD, TMC and chitosan hydrochloride did not cause any major changes in CBF.
Journal Article•
TL;DR: The first proposals for the use of electric current in drug delivery date from the mid 18th century and the technique was never widely adopted but always proved useful to some extent in solving particular drug delivery problems.
Abstract: The first proposals for the use of electric current in drug delivery date from the mid 18th century. Serious progress was made in the 19th century notably by Benjamin Ward Richardson (1828-1896), Hermann Munk (1839-1912), William James Morton (1846-1920), Stephane Leduc (1853-1939) and Fritz Frankenhauser (born 1868). Administration of metal ions as well as alkaloids was tried at that time. Until the early 20th century, current mediated drug delivery was known as "cataphoresis"; Frankenhauser is said to have introduced the term "iontophoresis" before 1908. Recently, researchers talk about "electrically-assisted transdermal drug delivery". The technique was never widely adopted but always proved useful to some extent in solving particular drug delivery problems. At the dawn of the 21st century, attempts are being made to achieve iontophoretic delivery of peptides and proteins.
Journal Article•
TL;DR: A new norditerpenyl ester, named Calotropterpenyl Ester, and two unknown pentacyclic triterpenoids, namely calotropursenyl acetate and calotropfriedelenylacetate have been isolated from the root bark of Calotropis procera.
Abstract: A new norditerpenyl ester, named Calotropterpenyl ester, and two unknown pentacyclic triterpenoids, namely calotropursenyl acetate and calotropfriedelenyl acetate have been isolated from the root bark of Calotropis procera. Their structures have been established as 6,10,14-trimethylpentadec-6-enyl-2',4',8',12',16'-pentamethyl nonadecane ester, urs-12,19(29)-diene-3 beta-yl acetate and friedelin-1-ene-3 beta-yl acetate, respectively, on the basis of spectral data analyses and chemical reactions.
Journal Article•
TL;DR: Curing at higher temperatures improves the polymer particles coalescence to a physically stable state and other stability aspects such as physical and chemical aging, migration of plasticizers and drugs and incompatibilities are also discussed.
Abstract: The formation of film coatings from aqueous polymer dispersions is a complex process, highly dependent on additives and process parameters. Release instability of modified release coatings from aqueous polymer dispersions is a frequently described problem that hinders the general application of such dispersions. However, if some important prerequisites are fulfilled, storage stability should be achievable. Most important are: (a) The appropriate plasticizing time has to be considered, incorporating sparingly soluble plasticizers in the dispersion. (b) Necessary pore formers increase the permeability of the coating to a desired and constant extent only if they are compatible with the polymer. (c) Coating in the fluidized bed at or slightly above the minimum film forming temperature may lead to only incomplete film formation. Curing at higher temperatures improves the polymer particles coalescence to a physically stable state. Other stability aspects such as physical and chemical aging, migration of plasticizers and drugs and incompatibilities are also discussed.
Journal Article•
TL;DR: There was a significant relationship between valerenic acids content and added valerian root for the standardized products but not for the non-standardised products.
Abstract: Thirty-one commercial valerian preparations available in Australia, including teas, tablets, capsules and liquids, were analysed by HPLC for valepotriates, valerenic acid and valerenic acid derivatives. The concentration of valerenic acid and its derivatives ranged from < 0.01 to 6.32 mg/g of product. Powder capsules, on average, contained the highest concentration of valerenic acids (2.46 mg/g) and liquids the lowest concentration (0.47 mg/ml). The mean concentration of valerenic acid in the five products standardized against valerenic acid (3.56 mg/g) was significantly higher than in the 26 non-standardized products (0.89 mg/g). There was a significant relationship between valerenic acids content and added valerian root for the standardized products but not for the non-standardised products. Valepotriates were found at low levels (< 1.0 mg/g) in some teas but were not detected in any of the finished products.
Journal Article•
TL;DR: The 13C NMR spectrum of the higher molecular weight polymer fraction revealed a 3',4'-dihydroxylated B-ring oxidation pattern and the 2,3-cis relative stereochemistry of the constituent flavan-3-ol units.
Abstract: From the aqueous acetone extract of the herb of Hypericum perforatum the flavanols catechin (1) and epicatechin (2), and the procyanidins A2 (9), B1 (3), B2 (4), B3 (5), B5 (6), B7 (7) and Cl (8) were isolated. Their structures were established as their peracetate derivatives, on the basis of chemical and spectral evidence. The 13 C NMR spectrum of the higher molecular weight polymer fraction revealed a 3',4'-dihydroxylated B-ring oxidation pattern and the 2,3-cis relative stereochemistry of the constituent flavan-3-ol units. The mean average molecular size of the polymers was estimated to be 4 to 5 flavan-3-ol units. The procyanidin pattern in comparison to that of Crataegus spec, is briefly discussed.
Journal Article•
TL;DR: The design, synthesis and antituberculosis activity of a series of 2-aryl-5-methylthio-1,3,4-thiadiazoles (5a-b), ethyl alpha-(5-aryl)-1-3, 4-thIadiazole-2-ylthio)acetates and related compounds are described.
Abstract: The design, synthesis and antituberculosis activity of a series of 2-aryl-5-methylthio-1,3,4-thiadiazoles (5a-b), ethyl alpha-(5-aryl)-1,3,4-thiadiazole-2-ylthio)acetates (8a-b) and related compounds are described. All of the compounds were tested against Mycobacterium tuberculosis strain H37Rv in comparison to rifampicin. Six compounds exhibited a very good activity (MIC < 6.25 micrograms/ml, % Inhibition = 100).
TL;DR: In this article, a series of semicarbazones and hydrazones were evaluated for anticonvulsant activity, and compound 2a emerged as the most active compound at a dose of 30 mg/kg in ScSty test.
Abstract: A series of semicarbazones and hydrazones were prepared and evaluated for anticonvulsant activity. Some compounds provided significant protection against maximal electroshock (MES) and subcutaneous strychnine induced seizures (ScSty). Compound 2a emerged as the most active compound at a dose of 30 mg/kg in ScSty test. The compounds 1a, 1g and 2a-e showed significant potentiation of sedative and hypnotic activity of pentobarbitone sodium. Thus compound 2a could serve as a prototype for future developments.
Journal Article•
TL;DR: The use of compound mixtures is a suitable method for improving the capacity in permeability screens, and further improvement of the throughput may be expected upon automatisation of permeability measurements using robotics combined with increased selectivity using LC-MS analysis.
Abstract: The purpose of this investigation was a study of simultaneous permeability measurement using compound mixtures (cassette dosing) as an alternative to single compound evaluation in order to increase the capacity of screens for intestinal drug permeability. Drug transport across Caco-2 monolayers was studied, both in the apical to basolateral and the basolateral to apical direction. The apparent permeability coefficients for ten compounds displaying different intestinal transport mechanisms were determined, first as single compounds and then as components of a mixture. Seven beta-adrenoceptor antagonists and baclofen were analysed simultaneously using reversed phase HPLC with UV detection, D-glucose and mannitol were measured by scintillation counting. The results indicated that the Papp from the mixture as donor phase correlated well with that of the single compounds and merely small changes in the Papp of each compound were observed between the single compound and mixture experiments. This minor variation resulted in a change in rank-order of the poorly permeable compounds in the mixture, however, without affecting their association with the permeability class according to the biopharmaceutics classification system (BCS). It can be concluded that the use of compound mixtures is a suitable method for improving the capacity in permeability screens. Further improvement of the throughput may be expected upon automatisation of permeability measurements using robotics combined with increased selectivity using LC-MS analysis.
Journal Article•
TL;DR: The role of uncondensed 1,2,4-triazine compounds and related heterobicyclic systems in AIDS and Cancer is reviewed in this article, where their medicinal applications are also reported.
Abstract: The role of uncondensed 1,2,4-triazine compounds and related heterobicyclic systems in AIDS and Cancer is reviewed. Their medicinal applications are also reported.
Journal Article•
TL;DR: It is postulated that lycopene could play an important role in the recovery of the integrity of biological membranes of the liver after radiation injury.
Abstract: Whole body exposure of male rats to 7 Gy gamma irradiation increased lipid peroxidation in the liver resulting in biomembrane damage of subcellular structures and release of their enzymes. This is evidenced by increase of thiobarbituric acid-reactive substances (TBARS) in mitochondria, lysosomes and microsomes. This was associated with a decrease in activity of the enzymes specific for each subcellular fraction; namely, mitochondrial glutamate dehydrogenase (GDH), lysosomal beta-glucuronidase and microsomal glucose 6-phosphatase. This was paralleled by an increased activity of these enzymes in the cytosol. Rats were supplemented with lycopene, a carotenoid present in tomatoes (5 mg/kg weight/day), by gavage, for 7 days before exposure to 7 Gy gamma irradiation. This resulted in diminishing amount of TBARS recorded for each subcellular structure in the liver of irradiated animals. Significant amelioration in the decrease recorded for the activity of mitochondrial glutamate dehydrogenase, lysosomal beta-glucuronidase and microsomal glucose 6-phosphatase was observed. This was associated with significant amelioration in the increase recorded for the activity of these enzymes in the cytosol. It is postulated that lycopene could play an important role in the recovery of the integrity of biological membranes of the liver after radiation injury.
Journal Article•
TL;DR: The results revealed that in spite of the high content of spray-dried powder in the tablets, the dissolution profiles of the extract did depend on the adjuvant used, and the filler/binder had the most important effect on the dissolution efficiency of the tablets.
Abstract: A 2 3 factorial design was used in order to evaluate the influence of some adjuvants on the dissolution profile of tablets containing high doses of Maytenus ilicifolia spray-dried extract. Tablets were prepared on a single punch tablet press using 15 mm flat punches by individual direct compression of 650 mg from each formulation containing 375 mg of the spray-dried extract. The factors investigated were disintegrant (croscarmellose sodium or sodium starch glycolate), lubricant (colloidal silicon dioxide or magnesium stearate) and filler/binder (microcrystalline cellulose or lactose). The dissolution profiles were analyzed to determine the dissolution kinetics, the dissolution half-lives (t 50% ), the similarity factor (f 2 ) and the dissolution efficiency (DE %), which was selected as the response criteria to evaluate the factorial design. The results revealed that in spite of the high content of spray-dried powder in the tablets, the dissolution profiles of the extract did depend on the adjuvant used. The filler/binder had the most important effect on the dissolution efficiency of the tablets.
Journal Article•
TL;DR: In this article, the authors evaluated three compounds, 2b, 4b and 4d, for the first and second level in vitro screening of Mycobacterium tuberculosis and mycobacteria avium in the TAACF Antituberculosis Screen Program.
Abstract: The compounds being reported in this paper have all been evaluated within the TAACF Antituberculosis Screen Program, and some of them have been shown to possess high growth inhibition activity against Mycobacterium tuberculosis and Mycobacterium avium in the run of the first and second level in vitro screenings. The three compounds which have shown a good SI (Selectivity Index) are 2b, 4b and 4d; in addition, 6,7-dimethyl-3-[4-(4'-nitrophenyl)piperazin-1-yl]quinoxaline-2-carbonitrilo 1,4-di-N-oxide (4b) is currently being tested within the in vivo antituberculosis screening in view of its very good in vitro activity.
Journal Article•
TL;DR: Examination of the gels in the biopharmaceutical model, which simulated the physiological conditions of the vagina, allowed determination of the mobility of the preparations in patients and confirmed the binding of lactic acid with basic polymers polyvinyl pyrrolidone K-90.
Abstract: In continuing the investigation of the binding of lactic acid with basic polymers polyvinyl pyrrolidone K-90 (PVP) was used. Use of PVP in mixtures with lactic acid in experimentally determined and calculated proportions allowed the preparation of gels with pH 3.8-4.4, i.e. maintaining the physiological conditions in the vagina. The viscosity of the methylcellulose gels increases proportionally to the amount of the PVP - lactic acid complex added. Examination of the gels in the biopharmaceutical model, which simulated the physiological conditions of the vagina, allowed determination of the mobility of the preparations in patients.
Journal Article•
TL;DR: A 7-factor 12-run Plackett-Burman screening design showed that all the seven factors affected, with varying order, the release of naproxen from its compressed tablets.
Abstract: The objectives of the present study were to screen the formulation and process variables for the preparation of extended release naproxen tablets with Eudragit L100-55. The tablets were prepared by compression of microspheres that were obtained by a coprecipitation technique. The process involved dissolution of naproxen and Eudragit L 100-55 in alcohol USP followed by the addition of an aqueous solution containing a surfactant and deaggregating agents. The mixture was stirred for a specified time period to obtain microspheres, which were filtered and air-dried to a constant weight. The microspheres were then compressed to obtain plain tablets with a diameter of 12 mm. A 7-factor 12-run Plackett-Burman screening design was employed to evaluate the main effects of homogenization time (X1), rate of water addition (X2), amount of polymer (X3), amount of precipitating solution (X4), concentration of electrolytes (X5), compression pressure (X6), and the concentration of lubricant (X7) on the rate of drug release. The response variable was cumulative percent of naproxen dissolved in 12 h in simulated intestinal fluid with constraints on responses that included percent yield, hardness, thickness, and the angle of repose. Mathematical relationship for percent of naproxen dissolved in 12 h (Y5) with various factors yielded the following polynomial equation; Y5 (% dissolved in 12 h) = 95.48 + 0.53 X1 + 3.51 X2 + 3.84 X3 - 3.80 X4 - 2.46 X5 - 2.90 X6 - 3.91 X7. The results showed that all the seven factors affected, with varying order, the release of naproxen from its compressed tablets.
Journal Article•
TL;DR: The addition within compatibility limits of the pore formers hydroxypropyl methylcellulose (HPMC) and hydroxy ethylcellulOSE (HEC) to coatings of the quaternary polymethacrylate dispersion Eudragit RS 30 D enables drug release to be controlled without problems.
Abstract: The addition within compatibility limits of the pore formers hydroxypropyl methylcellulose (HPMC) and hydroxy ethylcellulose (HEC) to coatings of the quaternary polymethacrylate dispersion Eudragit RS 30 D enables drug release to be controlled without problems. 20 and 15%, respectively, of these pore formers are suitable for release within 8 h of theophylline from pellets with a coating thickness of about 30 microns. A 10% addition of plasticizer, water soluble triethyl citrate (TEC) or water insoluble dibutyl phthalate (DBP), lowers the minimum film forming temperature (MFT) from 48 to 17 and 26 degrees C, respectively. The MFT is scarcely influenced by the pore formers. However, the plasticizers may modify the effect of the pore formers: HPMC is more effective in the presence of DBP. In spite of the preparation of the coatings at a bed temperature about 20 degrees C above MFT, the release from the diffusion pellets is not stable during storage. Only curing in an oven or in the fluidized bed up to a certain limiting release rate at 80 degrees C for 1 h results in stable products. Increased relative humidity allows reduction of the curing temperature. The water soluble additives polyoxy ethylene (PEG) and polyvinyl pyrrolidone (PVP) and insoluble additives are ineffective as pore formers.
Journal Article•
TL;DR: A series of appropriate aminoisopropanoloxy derivatives of 2-, 3- or 6-xanthone was synthesized and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (ScMet) assays and for neurotoxicity (TOX).
Abstract: A series of appropriate aminoisopropanoloxy derivatives of 2-, 3- or 6-xanthone was synthesized and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (ScMet) assays and for neurotoxicity (TOX). The most interesting result was the anticonvulsant activity of (±)-3-(2-propylamino)-1-[(2-methyl)-6-xanthonoxy]-2-propanol hydrochloride (10), which displayed anti-MES activity with a protective index (TD 50 /ED 50 ) of 0.80. Some of the obtained compounds were also tested for their effect on the circulatory system (influence on the non-working heart perfusion, protection against adrenaline induced-arrhythmia) and acute toxicity.
Journal Article•
TL;DR: A series of N-(5-phthalimidopentanoyl)-, N-[2-(2-ethoxy)acetyl]-, and N-(7-oxooctanoyal)-phosphono and phosphinoalanine derivatives has been synthesized and evaluated for inhibition of the D-glutamic acid-addressing enzyme (MurD) of peptidoglycan biosynthesis.
Abstract: A series of N-(5-phthalimidopentanoyl)-, N-[2-(2-ethoxy)acetyl]-, and N-(7-oxooctanoyl)-phosphono and phosphinoalanine derivatives has been synthesized and evaluated for inhibition of the D-glutamic acid-adding enzyme (MurD) of peptidoglycan biosynthesis.