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PubMed2000

Possible mechanism for drug retardation from glyceryl monostearate matrix system.

Lipophilicity was evaluated as a possible mechanism for drug retardation from a glyceryl monostearate matrix system. Lipophilicity of the glyceryl monostearate matrix system was studied using contact angle measurement of water droplets on the surface of compressed disks, extrudate ascension of water, and movement of water through a powder mixture packed in a high-performance liquid chromatographic (HPLC) column. Increase in glyceryl monostearate content resulted in an increase in water droplet contact angle, decrease in the rate of water ascending the extrudate, and increase in the pressure values as a function of flow rate of water moving through the powder mixture. These could be due to the increase in lipophilicity of the matrix, rendering the matrix less wettable. As a result, the rate of water penetration into the matrix decreased, and the drug release could be sustained.

Chemistry, Pharmaceutical↗
PubMed1999

Influence of pigment concentration and particle size on adhesion of an acrylic resin copolymer to tablet compacts.

The effects of the particle size and the concentration of pigments in aqueous polymeric dispersions on the adhesive properties of an acrylic resin copolymer were investigated. Aqueous polymeric dispersions containing up to 20% (v/v) pigment were coated onto hydrophilic and hydrophobic tablet compacts, and polymer adhesion was assessed using a novel butt adhesion technique. An inverse relationship was found between the particle size of the pigment present in the aqueous polymeric dispersion and film-tablet adhesion. As the particle size of the pigment increased, the adhesive strength of the polymer to the tablet compact decreased. Increased concentrations of the opacifying agent titanium dioxide in the acrylic dispersion resulted in stronger film-tablet adhesion. No clear relationship could be established between the wettability of the tablet compact by the pigmented polymeric dispersion and the strength of film-tablet adhesion. The hydrophobicity of the tablet compact was found to affect the glass transition temperature of the polymeric film to a greater extent than the particle size, morphology, or concentration of the pigment incorporated into the acrylic dispersion.

Acrylic Resins↗
PubMed2001

Characterization of the solubility and dissolution properties of several new rifampicin polymorphs, solvates, and hydrates.

Based on reports that tuberculosis is on the increase, this investigation into the physicochemical properties of rifampicin when recrystallized from various solvent systems was undertaken. Rifampicin is an essential component of the currently recommended regimen for treating tuberculosis, although relatively little is known about its solubility and dissolution behavior in relation to its solid-state properties. A rifampicin monohydrate, a rifampicin dihydrate, two amorphous forms, a 1:1 rifampicin:acetone solvate, and a 1:2 rifampicin:2-pyrrolidone solvate were isolated and characterized using spectral, thermal, and solubility measurements. The crystal forms were relatively unstable because except for the 2-pyrrolidone solvate, all the hydrated or solvated materials changed to amorphous forms after desolvation. Fourier transform infrared (FTIR) analysis confirmed the favorable three-dimensional organization of the pharmacophore to ensure antibacterial activity in all the crystal forms except the 2-pyrrolidone solvate. In the 2-pyrrolidone solvate, the strong IR signals of 2-pyrrolidone interfered with the vibrations of the ansa group. The 2-pyrrolidone solvate was the most soluble in phosphate buffer at pH 7.4. This solvate also had the highest solubility (1.58 mg/ml) and the fastest dissolution in water. In 0.1 M HCl, the dihydrate dissolved the quickest. A X-ray amorphous form (amorph II) was the least soluble and had the slowest dissolution rate because the powder was poorly wettable and very electrostatic.

Antibiotics, Antitubercular↗
PubMed2002

Application of fluidized hot-melt granulation (FHMG) for the preparation of granules for tableting; properties of granules and tablets prepared by FHMG.

The objective of this study was to investigate the properties of granules and tablets prepared by a novel Fluidized Hot-Melt Granulation (FHMG) technique. Macrogol 6000 (polyethylene glycol 6000, PEG 6000), macrogol 20000 (polyethylene glycol 20000, PEG 20000), and glyceryl monostearate (GMS) were used as binders with different levels of viscosity and water solubility. The properties of both granules and tablets were compared with those obtained using the Standard Tablet Formulation (STF, lactose/corn starch/hydroxypropylcellulose/ magnesium stearate: 66/30/3.5/0.5) for fluidized-bed granulation, which is widely used for wet granulation. To obtain suitable flowability as granules for tabletting, the content of the melting material should be approximately 10 w/w%. The rate of increase in the mean diameter of the granules during FHMG was affected by both the melting temperature and the viscosity of the melting material used in the granules. The compression properties of granules prepared by FHMG were also investigated, demonstrating that these granules had a high pressure transmittance. The hardness and the disintegration time of tablets obtained from granules prepared by FHMG were influenced by the properties of the melting material, such as its compaction behavior, solubility, and wettability. No significant differences of hardness were observed when compared to STF tablets. Tablets prepared from FHMG granules disintegrated within 15 min, whereas the STF tablets showed faster disintegration. It was also demonstrated that the hardness and disintegration time of tablets prepared from FHMG granules were not affected by the tablet porosity. Therefore, tablets with a constant quality may be obtainable under a wide range of compression forces. The results of this study suggested that FHMG is a useful method of preparing granules for tableting without using any solvents or water.

Drug Compounding↗
PubMed2002

Enhancement of dissolution rate and anti-inflammatory effects of piroxicam using solvent deposition technique.

Piroxicam solid depositions were prepared by means of the solvent deposition technique using different concentrations of microcrystalline cellulose as carrier material. The solvent deposition system (SDS) with drug to carrier ratio of 1:9 had a rapid dissolution rate in vitro. When this SDS was administered perorally to rats with a previous experimentally induced inflammation in their paws, it exhibited a pronounced anti-inflammatory action. X-ray diffraction and infrared (IR) spectroscopy showed no differences in the crystal state of piroxicam in SDS formulation and physical mixture of piroxicam and carrier. The increase in the dissolution rate and consequent enhancement of anti-inflammatory effect of piroxicam in SDS were attributed to the reduced particle size of drug deposited on the carrier and enhanced wettability of the particles brought about by the carrier.

Administration, Oral↗
PubMed2001

Effect of processing methods and heat treatment on the formation of wax matrix tablets for sustained drug release.

The objective of this study was to evaluate the effects of processing methods and heat treatment on matrix formation and subsequent drug release from wax matrix tablets for controlled release. Phenylpropanolamine hydrochloride (PPA) and Compritol were processed with appropriate diluent(s) using either dry blending (DB), wet granulation (WG), partial melt granulation (PMG), or melt granulation (MG). Then the tablets were heat-treated at 80 degrees C. Particle size distribution and compressibility, along with drug release, tablet micro-morphology, wettability, porosity, and tortuosity were investigated. The drug release was different for the four processing methods even though the tablet formulation was identical. Heat treatment further retarded drug release and its effect was related to the previous manufacturing processes. Scanning Electron Microscopy (SEM) showed that heat treatment redistributed the wax and formed a film-like structure covering drug and excipients. The contact angle of tablets made from DB, WG, and PMG methods increased after heat treatment, while that of tablets made from MG remained constant. Tablet tortuosity calculated from drug release rate constants increased dramatically after heat treatment. Drug release from the wax tablets with or without heat treatment was best described by the Higuchi equation. Different processing methods produced different matrix structures that resulted in different drug release rates. Heat treatment retarded drug release mainly by increasing tortuosity of the matrix. Contact angle measurement and SEM analysis indicated that heat treatment caused the wax to melt, redistribute, coat the drug and diluents, and form a network structure.

Delayed-Action Preparations↗
PubMed2000

Influence of emulsion droplet surface charge on indomethacin ocular tissue distribution.

The aim of this study was to compare the corneal penetration of indomethacin from Indocollyre [a marketed hydro-poly(ethylene glycol) (PEG) ocular solution] to that of a negatively and a positively charged submicron emulsion. Male albino rabbits were separated randomly into three groups and each group (N = 15) was treated with either one drop of radiolabeled 0.1% Indocollyre, or 0.1% indomethacin positively or negatively charged submicron emulsion, respectively. The rabbits were sacrificed at selected time points and the eyes were enucleated. The eyes were dissected into the different tissues: cornea, conjunctiva, aqueous humor, iris, lens, vitreous, sclera, and retina. The samples were weighed before radioactivity counting. Regardless of the preparation instilled, the highest concentration of indomethacin was achieved in the cornea followed by conjunctiva, sclera retina, and aqueous humor. However, the positively charged emulsion provided significantly higher drug levels than the control solution and negatively charged emulsion only in the aqueous humor and sclera-retina. Furthermore, the spreading coefficient of the positively charged emulsion on cornea is four times higher than that of the negatively charged emulsion. It was therefore deduced that the positively charged submicron emulsions have better wettability properties on the cornea compared to either saline or the negatively charged emulsion. The positive charge may prolong the residence time of the drop on the epithelial layer of the cornea and thus enable better drug penetration through the cornea to the internal tissues of the eye, as confirmed by the animal studies.

Absorption↗
PubMed2000

Direct Access to Plant Epicuticular Wax Crystals by a New Mechanical Isolation Method.

A new method for the isolation of wax crystals from plant surfaces is presented. The wax-covered plant surface, e.g., a piece of a leaf or fruit, is brought into contact with a preparation liquid, e.g., glycerol or triethylene glycol, and cooled to ca. -100 degrees C. When the plant specimen is removed, the epicuticular wax remains embedded in the frozen liquid. After it warms up, the wax layer can be captured on appropriate carriers for further studies. This isolation method causes very little stress on the wax crystals; thus the shape and crystal structure are well preserved. In many cases it is possible, by choosing a preparation liquid with appropriate wettability, to isolate either the entire epicuticular wax layer or only discrete wax crystals without the underlying wax film. These crystals are well suited for electron diffraction studies by transmission electron microscopy and high resolution imaging by atomic force microscopy. The absence of intracuticular components and other impurities and the feasibility of the selective isolation of wax crystals enable improved chemical analysis and a more detailed study of their properties.

Journal Article↗
PubMed2000

Respiratory-related quality of life: relation to pulmonary function, functional exercise capacity, and sputum biophysical properties.

One of the difficulties in assessing mucoactive therapy is selecting clinical outcome variables that reflect the impact of clearing airway secretions on quality of life (QOL). Petty and colleagues developed a questionnaire designed to evaluate the clinical impact of mucoactive therapy in patients with chronic bronchitis (CB). We evaluated this questionnaire in a multicenter study of a mucolytic medication used in patients with CB and hypothesized that spirometry, exercise capacity, and sputum clearability changes would correlate with QOL changes. This was a multicenter trial in 159 patients with stable CB (111 completed the 16-week study). Spirometry, plethysmography, the 6-minute walk test (6MWT), and Petty score as a measure of QOL were assessed at each visit. Sputum was collected at each visit. Cough transportability was measured in a cough machine, and mucociliary transportability was measured on the frog palate. Cohesivity was measured in a filancemeter, interfacial tension by de Noüy ring, and wettability by contact angle analysis. Within the entire data set of 694 evaluations, there was no correlation between pulmonary function and QOL. There was an inverse correlation with distance covered in a 6MWT (R(2) = 0.041, p < 0.0001). Sputum CTR was directly correlated with QOL (R(2) = 0.027, p < 0.0001). Change from baseline (mean of first three visits) was computed and compared the change in the mean of values at the 8- and 12-week visits (n = 108 sets of data pairs). This was analyzed as a percentage of change for continuous measurements, and as QOL is normative, we calculated the absolute change in QOL. There was no relation between QOL and 6MWT changes. There was an inverse relation between change in forced expiratory volume in 1 second and QOL (R(2) = 0.092, p = 0.0021) as well as between forced vital capacity and QOL (R(2) = 0.05, p = 0.024). There was a direct relation between CTR and QOL (R(2) = 0.039, p = 0.048). The relation between QOL and 6-minute walk distance was expected but weak. The consistent relation between CTR and QOL (suggesting that improved CTR of sputum is associated with decreased QOL) is difficult to explain. A change in forced expiratory volume in 1 second and forced vital capacity did correlate with a change in QOL. There is a need for a good QOL tool to evaluate mucus clearance devices or medications. The Petty questionnaire was designed specifically for this task, but the effect on sputum properties by current mucoactive agents may be too small to elicit a significant change in the Petty score.

Analysis of Variance↗
PubMed1992

Assessment of dermal and inhalation exposure to zineb/maneb in the cultivation of flower bulbs.

In bulb farming the use of pesticides for crop protection and bulb disinfection is extensive. To estimate long-term occupational exposure to pesticides, generic levels of exposure specific to the method of working were needed. In order to derive these values, dermal and inhalation exposure to the fungicide mixture zineb/maneb was assessed for different methods of mixing and loading a wettable powder formulation. Further, dermal exposure was also assessed for two methods of disinfection of bulbs. Observed exposure was expressed in terms of method-specific levels of exposure, which makes it possible to compare exposure resulting from different methods of working, with respect to the amount of pesticide handled, or whether ladling the pesticide with a scoop or dipping the bulbs using baskets resulted in high exposure. Moreover, the relative importance of dermal and inhalation exposure routes was estimated. The results show that during mixing and loading with bare hands dermal exposure is by far the greater contributor (greater than 99%) to the total estimated exposure. Comparing these results and also some preliminary results of the dermal protection provided by working gloves, with tentative health-based limit values of exposure, emphasize the need for a programme on appropriate dermal protection.

Air Pollutants, Occupational↗
PubMed1992

Differences in the response of German cockroach (Dictyoptera: Blattellidae) field strains to vapors of pyrethroid formulations.

Late-instar German cockroaches from an insecticide-susceptible field strain (Fairbanks) and four pyrethroid-resistant field strains were exposed to vapors of a cyfluthrin flowable concentrate (FC) and the formulation blank (formulation without the active ingredient). Experiments with other pyrethroid formulations were done with the Fairbanks strain and an insecticide-resistant field strain (K-851) because these strains exemplified the maximum interstrain variation in experiments with the FC. In these experiments, I used a cyfluthrin wettable powder (WP) and its blank, a cyfluthrin emulsifiable concentrate (EC), and a permethrin aerosol and its blank. Vapors of the FC and its blank caused the most rapid dispersal. Dispersal induced by vapors of the WP, EC, and aerosol formulations was low and variable. In general, less of a dispersal response occurred in the resistant strains than in the susceptible strain. The strain mostly highly resistant to pyrethroids (K-851) dispersed slowly compared with the other resistant strains in experiments with the FC and its blank. When vapor-induced dispersal was relatively low (less than 50%), a trend was still evident towards less dispersal in the K-851 strain than in the Fairbanks strain. Although dispersal in experiments with the FC did not differ significantly from that in experiments with the FC formulation blank, mean percentage dispersal at the end of the experiments was higher with the formulation blanks than with the complete formulations in experiments with the WP and permethrin aerosol.

Animals↗
PubMed1993

Relationship between insecticide resistance and performance in choice tests of field-collected German cockroaches (Dictyoptera: Blattellidae).

Topical application (LD) and time-mortality response (LT) methods were used to determine resistance levels of field-collected strains of the German cockroach, Blattella germanica (L.). LD50s for chlorpyrifos were determined for seven strains. LT50s and LT90s with eight insecticides were determined for another three strains. Resistance ratios (RR) of > 10 to chlorpyrifos (LD50) were directly related to a significant decrease in activity in Ebeling choice-box tests. Using the LT method, the three field-collected strains were shown to possess zero to moderate resistance at the RR50 level (0.9-5.3) to organophosphates, moderate to high resistance to (1.4->21.0) to carbamates, moderate to high resistance (4.3-20) to cypermethrin, and high resistance (>17->35) to synergized pyrethrins. When the three field-collected strains were tested in choice boxes, RR50S of 1.2-2.2 for chlorpyrifos and 2.5-5.3 for diazinon directly related to significantly lower efficacy. Low-level propoxur resistance (RR50 of 1.4-2.3) also reduced choice-box efficacy, but an RR50 of 0.9-1.3 for acephate did not reduce its performance. Cypermethrin deposits used in choice tests killed cockroaches exhibiting RR50s as high as 20 in the lethal time test, perhaps because resistance mechanisms could not detoxify the exceptional activity of the active ingredient formulated as a wettable powder. Because they were repellent, residual deposits of pyrethrins resulted in poor efficacy in choice tests with either susceptible or field-collected strains. Strains with low-level physiological resistance as measured by the time-mortality response method survived insecticide exposure in choice-box tests to certain organophosphate and carbamate insecticides, indicating that these compounds would not be effective in the field.

Animals↗
PubMed1996

Activity of insecticides applied to turfgrass to control adult cat fleas (Siphonaptera:Pulicidae).

A bioassay was developed to determine the efficacy of insecticides against adult cat fleas, Ctenocephalides felis (Bouché), on turfgrass. Activity was assessed by exposing adult fleas to treated and untreated disks of turf for 24 h, 1 and 7 d after treatment. Filter paper, a representative nonwaxy, porous substrate was bioassayed in similar fashion 1 d after treatment to confirm insecticide activity. Results demonstrated the relative efficacy of insecticides applied to turf at different rates as well as differences among insecticides. Of 10 insecticides tested, chlorpyrifos wettable powder and emulsifiable concentrates consistently provided greatest kill of adult fleas. Although initially active, pyrethroid insecticides and diazinon generally showed significant declines in residual activity by day 7. Possible reasons for differences in activity are discussed.

Animals↗
PubMed1997

Effect of ecdysteroid UDP-glucosyltransferase gene deletion on efficacy of a baculovirus against Heliothis virescens and Trichoplusia ni (Lepidoptera: Noctuidae).

Laboratory, greenhouse, and field studies were conducted to characterize the biological activity of a genetically altered form of Autographa californica (Speyer) nucleopolyhedrosis virus (AcNPV). The altered baculovirus (vEGTDEL) had a deletion in the ecdysteroid UDP-glucosyltransferase gene. Results from bioassays conducted with neonate and 3rd-instar tobacco budworm, Heliothis virescens (F.), as well as with 3rd-instar cabbage looper, Trichoplusia ni (Hübner), showed vEGTDEL caused larval death slightly, but significantly, quicker than AcNPV. Based on supposition (LT50 values were not calculated), it appeared that larval mortality occurred 0.5-1.0 d faster following exposure to vEGTDEL versus AcNPV. Greenhouse studies conducted against H. virescens on cotton showed that hastened virulence exhibited by vEGTDEL led to improved plant protection versus AcNPV. For example, following 5 weekly sessions of foliar application and H. virescens artificial infestation, cotton treated with wettable powder formulations of vEGTDEL or AcNPV at 2.5 x 10(12) OB/ha averaged 25.7 and 61.8% damaged flower buds, respectively. Although vEGTDEL tended to provide more consistent control of T. ni than AcNPV in greenhouse and field trials conducted on leafy vegetables, differences in efficacy between the 2 baculoviruses were marginal and usually not statistically significant. Generally, results from these studies suggest that genetic modification of NPVs to hasten their lethal effect may be a promising strategy for improving the insecticidal properties of the insect-specific pathogens.

Animals↗
PubMed1997

Evaluation of methods of insecticide application for control of smokybrown cockroaches (Dictyoptera: Blattidae).

The insecticide components of a previously developed integrated pest management system for smokybrown cockroaches, Periplaneta fuliginosa (Serville), were tested individually and at reduced application rates in 4 separate trials over 2 yr. A 2-bait combination (pellet and gel baits) did not significantly reduce cockroach abundance more than a single constituent bait alone. A targeted spray of trelamethrin was significantly less effective than a 2-bait combination. Residual activity of insecticides was determined with American cockroaches, P. americana (L.), in a laboratory bioassay. Chlorpyrifos wettable powder remained active < 12 d in the field, after which time its activity was not different from an experimental control (no insecticide residues), whereas chlorpyrifos pellet and hydramethylnon paste baits retained initial activity for > 27 d. Nematodes [Steinernema carpocapsae (Weiser)] applied as a spray solution did not effect the abundance of smokybrown cockroaches, and no cockroaches were recovered that exhibited nematode infection. Time needed to apply various insecticide treatments did not differ substantially (15-25 min per house), even for lower application rates.

Animals↗
PubMed1998

Evaluation of three (Z)-9-tricosene formulations for control of Musca domestica (Diptera: Muscidae) in caged-layer poultry units.

A field trial comparing the effectiveness of toxic targets impregnated with different formulations of the Musca domestica L. female sex pheromone (Z)-9-tricosene was conducted in a caged-layer, deep-pit poultry unit in southern England. Targets baited with 5 g of technical grade (Z)-9-tricosene, or 5 g of a 40% polymer bead formulation, caught significantly greater numbers of M. domestica than control targets. This increase in attractiveness of the pheromone-impregnated targets persisted for at least 24 wk. However, mean daily catch rates of M. domestica at targets baited with 5 g of a 2% wettable powder formulation did not significantly differ from control levels. Technical grade and bead formulations of the pheromone attracted significantly more males than females. However, the catches of female M. domestica at these pheromone-impregnated targets were significantly greater than female catches at control targets. Monitoring with sticky cards indicated that the introduction of toxic targets successfully suppressed adult M. domestica population density for up to 13 wk. Possible hypotheses explaining the effect of (Z)-9-tricosene on female attraction are discussed.

Alkenes↗
PubMed2004

Biological control of Lobesia botrana (Lepidoptera: Tortricidae) larvae by using different formulations of Bacillus thuringiensis in 11 vine cultivars under field conditions.

This work describes the results of an experiment that was conducted in the vineyard of the American Farm School, Thermi, Thessaloniki Greece, during 2001. Its aim was to study the efficacy of two formulations of Bacillus thuringiensis Berliner (wettable powder and dust) to control the larvae of Lobesia botrana Denis & Schiffermueler (Lepidoptera: Tortricidae). The experimental results showed that the two formulations of B. thuringiensis are significantly more effective than the control, the dusting being more effective in most cultivars (Asyrtico, Sauvignon blanc, Debina, Athiri, Agiorgitico, Limnio, Syrah, and Cabernet sauvignon), and the spraying in a few cultivars (Xinomavro, Roditis, and Chardonnay). Dusting in the blue-black cultivars was found to be more effective than spraying, this not being the case in the yellow-green cultivars. This fact should be taken into consideration when cultivars of different color were planted in the same field. Single dusting proved to be better in cultivars with loose, average and dense berry cluster compactness, whereas double spraying gave better results in compact cultivars.

Animals↗
PubMed1989

Activity of insecticides against the preemerged adult cat flea in the cocoon (Siphonaptera: Pulicidae).

The activity of insecticides against the adult cat flea, Ctenocephalides felis (Bouché), inside the cocoon (preemerged) was determined by spraying the cocoons directly and observing subsequent emergence of adults over the next 14 d. Direct sprays of 0.5% trimethacarb wettable powder (WP) and chlorpyrifos emulsifiable concentrate (EC) and WP provided greater than 70% kill. The order of activity against the preemerged adult exposed to direct sprays was organophosphates greater than carbamates greater than pyrethroids. In general, pyrethroids and proprietary aerosols failed to kill preemerged adults. Even though most sprays did not kill preemerged adults, they stimulated adult emergence from cocoons. Preemerged adults placed in the nap of carpet were not killed by chlorpyrifos, diazinon, or propetamphos sprays; the carpet protected them effectively.

Animals↗