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At least 793 records · Page 44Linked to original sources
PubMed2006

Development of a respirable, sustained release microcarrier for 5-fluorouracil II: In vitro and in vivo optimization of lipid coated nanoparticles.

The release rate of 5-fluorouracil (5-FU) from lipid-coated nanoparticles (LNPs) was determined to develop a respirable delivery system for use as adjuvant (postsurgery) therapy for lung cancer. LNPs were prepared by spray drying, and the in vitro release was measured by microdialysis. The composition of the core and shell affected the release rate. Increasing the core diameter at constant shell thickness and increasing shell thickness at constant core diameter reduced the release rate, suggesting that the lipid shell is the rate limiting step for the release of 5-FU. A model consisting of a sequential zero-order/first-order dependence on time from polydispersed cores within polydispersed shells was developed to describe the release. Based on studies of the effect of geometry of the layered particles, the optimal formulation was identified as a 600-nm diameter 5-FU/poly-(glutamic acid) core with a 200-nm thick tripalmitin/cetyl alcohol shell. This system is readily aerosolized by ultrasonic atomization, which did not change the release properties. Preliminary instillation and inhalation delivery studies to the hamster resulted in lung levels of the particles and 5-FU that were near the desired values. Through this effort, a sustained-release, respirable delivery system for adjuvant therapy of lung cancer in humans may ultimately be realized.

Administration, Inhalation↗
PubMed2006

Development of a respirable, sustained release microcarrier for 5-fluorouracil I: In vitro assessment of liposomes, microspheres, and lipid coated nanoparticles.

The release rate of 5-fluorouracil (5-FU) from liposomes, microspheres, and lipid-coated nanoparticles (LNPs) was determined by microdialysis to investigate their use as a respirable delivery system for adjuvant (postsurgery) therapy of lung cancer. 5-FU was incorporated into liposomes using thin film hydration and into microspheres and LNPs by spray drying. Primary particle size distributions were measured by dynamic light scattering. Liposomes released 5-FU in 4-10 h (k(1) = 0.44-2.31/h, first-order release model). Extruded vesicles with diameters less than one micron released 5-FU more quickly than nonextruded vesicles. With poly-(lactide) (PLA) and Poly-(lactide-co-glycolide) (PLGA) microspheres, slower release rates were observed (k(1) = 0.067-0.202/h). Increasing the lactide:glycolide ratio (50:50-100:0) resulted in a progressive decrease in the release rate of 5-FU. poly-(lactide-co-caprolactone) (PLCL) microspheres released 5-FU more rapidly compared to PLGA systems (k(1) = 0.254-0.259/h). LNPs formulated with polymeric core excipients had lower release rates compared to monomeric excipients (k(1) = 0.043-0.105/h vs. k(1) = 0.192-0.345/h). Changing the lipid chain length of the shell lipid components had a relatively minor effect (k(1) = 0.043-0.129/h). Overall, these systems yielded a wide range of delivery durations that may be suitable for use as an inhalation delivery system for adjuvant therapy of lung cancer.

Administration, Inhalation↗
PubMed2006

Manipulation of beclomethasone-hydrofluoroalkane interactions using biocompatible macromolecules.

The aim of this work was to physically stabilise beclomethasone dipropionate (BDP) microparticles within a hydrofluoroalkane (HFA) propellant using biocompatible polymers in order to allow the efficient delivery of the steroid to the airways from a pressurised metered dose inhaler (pMDI). BDP microparticles were coated with a number of different "amphiphilic" macromolecular excipients by spray-drying an aqueous BDP suspension in which the excipients were dissolved. The physical stability of the coated BDP microparticles was assessed both indirectly using a twin-stage impinger (TSI) and directly using "in-situ" laser diffraction particle size analysis in a range of nonpolar solvents. The solubility of the formulation excipients within a number of the nonpolar vehicles was determined using an internally manufactured filtration rig and the influence of zeta potential within the microparticle suspensions measured in a series surrogate nonpolar systems. The size of the pure BDP microparticles increased significantly (p < 0.05, ANOVA) from 3.13 +/- 0.15 microm to 9.86 +/- 0.50 microm upon suspension within a nonpolar HFA solvent. However, the addition of poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) to the BDP microparticles dramatically reduce this aggregation leading to the production of physically stable suspensions with excellent aerosolisation properties (Stage 2 deposition >40% in the twin-stage impinger). It is postulated that the enhanced physical stability observed when PVA and PVP are coated onto BDP microparticles is partially as a result of steric stabilisation in HFA solvents. However, the large zeta potential associated with the nonpolar microparticle suspensions suggest that charge stabilisation may also influence the physical stability within these systems.

Aerosol Propellants↗
PubMed2006

Penetration of crystalline powder particles into excised human skin membranes and model gels from a supersonic powder injector.

The penetration of crystalline ibuprofen particles into excised human skin membranes and model target gels on actuation with the PowderJect ND1 ballistic needle-free injector has been examined. The deliverable dose of powder exiting the device is approximately 50% of the total cassette loading; the rest is lost via a gap forced open between the injector base and the surface of the target gel. It could be shown that substantial comminution of two different ibuprofen particle size fraction (38-53 microm, 53-75 microm) occurs within the injector on actuation. This resulted in an equiparation of the two initially different size fractions. Reduced comminution occurs with an ibuprofen/PVP (95:5) particulate formed by spray-drying/compaction/milling. On actuation into excised human skin membranes approximately 37% of cassette dose is recovered from the stratum corneum by stripping, and only 3% from the epidermis. It is concluded that powder delivery is mainly intra-epidermal with few particles fully breaching the stratum corneum. This is a consequence of the relative magnitude of the particle diameter (approximately 48 microm) and the stratum corneum thickness (approximately 10 microm). A 'soft' polyethylene glycol monolayer target gel gives the closest total percentage recovery of powder to that seen with the excised human skin membranes. Bilayer gels differentiated between surface impact/retention and penetration, but were difficult to handle. Powder penetration studies should therefore preferentially to be performed with human skin-membranes.

Administration, Cutaneous↗
PubMed2006

Novel colon-specific microspheres with highly dispersed hydroxycamptothecin cores: their preparation, release behavior, and therapeutic efficiency against colonic cancer.

To increase therapeutic efficiency of hydroxycamptothecin (HCPT) against colonic cancer and decrease its side-effects, highly dispersed HCPT was first incorporated in fast release microspheres. HCPT in the microspheres showed a solubility two times larger, and its cumulative release rate for 24 h in simulated colonic juice 140 times higher than that of free HCPT. The microspheres were then coated with a layer of Eudragit S100 by air suspension spray-drying method with a self-designed device to obtain colon-specific microspheres (HCPT-CSMS). The mean particle size of the microspheres was 200 microm before coating and 230 microm after coating. The in vitro cumulative release results for HCPT-CSMS in simulated gastric juice for 2 h, in simulated enteric juice for 4 h, and in simulated colonic juice for 18 h showed that over 60% of total HCPT released in simulated colonic juice in the initial 5 h. Animal tests with per os (po) administration showed that free HCPT was mainly absorbed in stomach and small intestine, while the HCPT in HCPT-CSMS was mainly delivered and absorbed in colon. po administration of HCPT-CSMS to nude mice with colonic cancer showed a cancer inhibition rate of 61.4% compared to 39.8% for free HCPT.

Animals↗
PubMed1975

Effect of physical properties on compression characteristics.

The tranmission of force to the die wall was measured by a piezoelectric sensor, and the compression cycles of lactose granules of different shapes were compared. In addition, a nearly spherical fraction of spray-dried lactose was similarly compared with a crystalline sample. Better tablets were formed when the conversion of axial to radial pressure was high and the residual pressure on the die wall remained after removal of the top punch. With acetaminophen and phenacetin, the pressure on the die wall was low, as was the residual pressure, and capping occurred in both cases. With direct compression acetaminophen, higher die wall pressure was produced and capping did not occur. It is considered that these results can be explained by the ease with which the more nearly isodiametric particle can rearrange under pressure and by the elastic properties of the solid.

Acetaminophen↗
PubMed1976

Effect of variation in compaction force on properties of six direct compression tablet formulations.

The effect of variation in compaction force on six direct compression tablet matrixes was investigated. An instrumented tablet press allowed direct measurement of applied and ejection forces. Hardness, apparent tablet density, and disintegration times also were determined. The disintegration time of spray-dried lactose tablets was essentially independent of compaction force. However, in the other systems investigated, the properties studied showed varying types of dependence on compaction pressure. A direct compression formula was developed and exhibits a decrease in disintegration time as compaction force is increased.

Chemistry, Pharmaceutical↗
PubMed1977

Application of gluconolactone in direct tablet compression.

Gluconolactone was evaluated as an excipient for tablets prepared by direct compression using various drugs known to be difficult to compress. The physical properties of the tablets were evaluated after compression and after storage and were satisfactory. Comparative studies were conducted between gluconolactone and anhydrous lactose, a common direct compression diluent, for development of static charges during blending, flow, drug distribution, drug stratification, color distribution, compressibility, and preservation against mold growth. Gluconolactone possesses those properties necessary to produce high quality tablets by the direct compression process. Separate powdered mixtures of aspirin USP with gluconolactone, anhydrous lactose, spray-dried lactose, mannitol, and sorbitol were stored at various humidities and temperatures for specified periods and tested for the integrity of aspirin. Gluconolactone contributed least to the degradation of the drug as compared to other excipients studied. A preliminary in vivo study also was conducted on the bioavailability of aspirin from separate and similar mixtures with gluconolactone, anhydrous lactose, and starch. Gluconolactone did not show any inhibitory effect on aspirin absorption.

Animals↗
PubMed1979

Conductivity and hardness changes in aged compacts.

Batches of sodium, potassium, and ammonium chloride tablets containing no excipients and spray-dried lactose tablets containing 0.5% magnesium stearate were stored at 20 and 76% relative humidity. Electrical resistance and hardness measurements were made within 1 hr after compression and at intervals during a 45-day period. Hardness values of sodium, potassium, and ammonium chloride tablets stored at 20% relative humidity increased from 70 to 200% at 45 days, while conductances decreased 10-fold. Tablets stored at 76% relative humidity showed no increases or slight decreases in hardness with slight increases in conductance. Lactose tablets decreased slightly in hardness with corresponding increases in conductance.

Ammonium Chloride↗
PubMed1981

Microencapsulation and fabrication of fuel pellets for inertial confinement fusion.

Various microencapsulation techniques were evaluated for fabrication of thermonuclear fuel pellets for use in existing experimental facilities studying inertial confinement fusion and in future fusion-power reactors. Coacervation, spray drying, in situ polymerization, and physical microencapsulation methods were employed. Highly spherical, hollow polymeric shells were fabricated ranging in size from 20 to 7000 micron. In situ polymerization microencapsulation with poly(methyl methacrylate) provided large shells, but problems with local wall defects still must be solved. Extension to other polymeric systems met with limited success. Requirements for inertial confinement fusion targets are described, as are the methods that were used.

Capsules↗
PubMed1984

Effect of compressional force on tablets containing cellulosic disintegrators I: Dimensionless disintegration values.

Spray-dried lactose tablets containing cellulosic disintegrators or microcrystalline cellulose were compressed at different compressional forces. USP disintegration times were measured as a function of pH and compressional force. Two dimensionless quantities were derived from the experimentally determined disintegration times, and their utility in the study of tablet formulations was demonstrated. These dimensionless quantities were used to assess the effect of compressional force and pH on disintegration behavior as well as to compare disintegrator efficiency. Two internally cross-linked sodium carboxymethylcellulose disintegrators were found to be the most efficient; their efficiency increased with increasing compressional force at all pH values.

Cellulose↗
PubMed1989

Preliminary studies of the development of a direct compression cellulose excipient from bagasse.

Bagasse is an unused by-product in cane sugar manufacture. Bagasse from sugar cane manually harvested in Indonesia was transformed to pulp by mechanical means and repeated autoclaving in 1.4% NaOH. It was then subjected to cycles of bleaching with hypochlorite and acid hydrolysis with 2.5 M HCl to produce 'microcrystalline' cellulose (MCC). Extraction of waxes by petroleum ether was necessary in order to improve the disintegration properties of tablets made from this material, DICEB III. When the bagasse-derived cellulose was reconstituted by recombining different proportions of selected sieve cuts to have a similar sieve size distribution as the commercially available MCC, Avicel PH102, it was found that the latter and DICEB III also had similar crystallinity as measured by X-ray powder diffraction (degree of crystallinity 2.8 +/- 0.2). The crystallinity and flow index were also relatively insensitive to most of the changes in the manufacturing procedure, indicating that the production process was quite robust. Directly compressed tablets were made containing 50 mg of caffeine and 500 mg of either Avicel PH102 or DICEB III to approximately the same hardness (11.6 +/- 1.1 and 13.7 +/- 0.5 kPa, respectively). They displayed similar satisfactory disintegration and dissolution behavior. However, DICEB III required greater compaction pressures than Avicel PH102, perhaps because the former was not spray dried to give spherical agglomerates of particles of uniform size as the commercial product. Rather, DICEB III consisted mainly of single irregular particles. Further work is required to improve the new excipient and to explore if the bagasse from mechanically harvested sugar cane (often contaminated by soil) could also be used for production of MCC.

Caffeine↗
PubMed1993

Degradation and release properties of pellets fabricated from three commercial poly(D,L-lactide-co-glycolide) biodegradable polymers.

Poly(D,L-lactide-co-glycolide, 50:50) samples of similar molecular weight were obtained from three commercial sources and were characterized by gel permeation chromatography, differential scanning calorimetry, X-ray powder diffraction, viscometry, and proton nuclear magnetic resonance spectroscopy. Pellets were prepared by melt-pressing spray-dried polymer with a 4-mm standard concave punch and die set and a thermostated holder of original design. Amaranth (5% w/w) was incorporated in pellets used for release studies. Degradation and release studies were conducted at 37 degrees C in pH 7.2 phosphate buffered saline. The molecular weights of all polymers were found to decrease continuously after exposure to phosphate buffered saline. All polymers showed two distinct regions of molecular weight decrease. Mass loss experiments for all polymers resulted in sigmoidal curves typical of polymers undergoing bulk hydrolysis. The onset of mass loss (defined as 10% mass loss) was found to differ by as much as 6 days among the three polymers studied. The release studies showed an initial burst of release followed by a period of 15-25 days during which little or no dye was released. A second phase of release followed, lasting approximately 10 days, until all dye was released. The time at which release began slightly preceded the onset of mass loss.

Buffers↗
PubMed2006

Susceptibility of adult Coccinella septempunctata (Coleoptera: Coccinellidae) to insecticides with different modes of action.

Five insecticides (pyriproxifen, imidacloprid, deltamethrin + heptenophos, lambda-cyhalothrin and Bacillus thuringiensis Berliner subsp. tenebrionis) were examined in the laboratory for their acute detrimental side-effects at field rates on adult seven-spot ladybird beetle, Coccinella septempunctata L. The toxicity of the preparations was determined by measuring the acute surface contact effects (dried spray on leaves of Philadelphus coronarius L.), except for B. thuringiensis where mixed pollen was treated. Four to six concentrations were tested (pyriproxifen 12.5, 25, 50, 100, 200, 400 mg AI litre(-1); imidacloprid 62.4, 125, 250, 500 mg AI litre(-1); deltamethrin + heptenophos 26.4, 53.1, 106.3, 212.5 mg AI litre(-1); lambda-cyhalothrin 1.1, 3.4, 10, 30 mg AI litre(-1); B. thuringiensis 1.5, 3.0, 12.0, 48, 192, 768 mg AI litre(-1)), with 22 adults exposed per concentration. All tests were conducted in the laboratory of the Plant Protection Department (University of Debrecen, Hungary) at 22-25 degrees C, 40-60% RH, under a 16:8 h light:dark photoperiod in 1998-1999. Data were analyzed by probit analysis, probit transformation and analysis of variance. According to different categories of evaluation, pyriproxifen, imidacloprid and B. thuringiensis subsp. tenebrionis seem to be safe for C. septempunctata adults but the other two preparations were moderately harmful to them, which requires further semi-field or field tests to measure their real effect under field conditions.

Animals↗
PubMed2004

Evaluation of the antiherpetic activity of standardized extracts of Achyrocline satureioides.

Traditionally, Achyrocline satureioides or 'marcela' has been used in South America for the treatment of several disorders. For the present study, three spray-dried extracts (N1, N2 and N3) were used, all of them prepared with 50% of an hydroethanolic extract rich in flavonoid compounds and 50% of blends of different adjuvants. The cytotoxic concentration which causes destruction in 50% monolayer cells (CC50) was 62.5 microg/ml for the three extracts. The antiviral activity was evaluated by using two different strains of herpes simplex virus (HSV-1) and the best results were obtained with KOS strain and N2 extract. Studies concerning the mechanism of the antiherpetic activity demonstrated that N2 extracts showed no virucidal effect or activity on cellular receptors. HSV-1 DNA synthesis was not inhibited. The antiherpetic activity occurred between the second and ninth hour of the virus replication cycle, probably indicating a perturbation on late stages of this cycle.

Achyrocline↗
PubMed2026

Low-Carbon-Residue Multi-Principal-Element Magnetic Alloys for Excellent Microwave Absorption.

Magnetic alloy/carbon composites are promising microwave absorbers due to abundant interfaces and multiple loss mechanisms. However, reducing carbon content while maintaining uniform magnetic component distribution remains challenging. We report a spray-drying strategy to address this. By tuning nitrate precursor ratios and optimizing thermal treatment, we synthesize low-carbon alloy/oxide microspheres with uniformly distributed alloy phases. Limiting carbon content improves impedance matching, while selective nitrate precipitation creates a magnetic alloy architecture that suppresses nanoparticle agglomeration and enhances interfacial polarization. For this multiscale synergistic polarization is achieved: highly conductive Cu maximizes conduction loss, insulating Al2O3 buffers impedance, and Mn provides abundant polarization centers. The resulting microspheres exhibit tunable, exceptional performance. The attenuation-dominated FeCuMn system achieves -48.2&#xa0;dB minimum reflection loss at 1.5&#xa0;mm thickness. The impedance-matched FeCuAl system delivers an ultra-broad effective absorption bandwidth (EAB) of 5.12&#xa0;GHz. Additionally, the FeAlMn system demonstrates superior polarization miniaturization for optimal absorption at extremely thin matching thicknesses. This work provides a practical strategy for designing electromagnetic composite structures with tunable component distribution.

customizable multicomponent↗
PubMed1990

Teratogenic effects of maternal biotin deficiency on mouse embryos examined at midgestation.

Pregnant mice were fed a basal diet that not only did not contain biotin, but also contained the spray-dried egg white including avidin that caused the biotin deficiency. The effects of maternal biotin deficiency on craniofacial and limb development in embryos were examined at two stages of midgestation. On day 12.6 of gestation, male and female embryos weighted less and digit development was retarded in the biotin-deficient group. On day 15.6 of gestation (dg), the embryos also weighted less and external malformations, such as micrognathia (94.8%), micromelia (41.4%), and exencephaly (11.4%), were observed. The inhibition of palatal and digit formation by biotin deficiency at midgestation is responsible for later formation of cleft palate and micromelia. On dg 12.6 the liver biotin level of biotin-deficient dams was reduced to 20% of control values. Interestingly, the biotin content of the whole embryonic body was about ninefold greater than liver biotin levels in their dams.

Animals↗
PubMed2000

Stabilization and preservation of Lactobacillus acidophilus in saccharide matrices.

Lyophilization and vacuum- or spray-drying are some of the most useful techniques for preserving foods, agricultural products, and pharmaceuticals. Biological materials, however, can be irreversibly damaged during these treatments. Therefore, it is essential to design protective agents to preserve protein activity and cell viability. In this paper we examine the use of alpha, alpha-trehalose-borate systems as protectants for Lactobacillus acidophilus during freeze- and vacuum-drying. Trehalose was found to be an effective protectant for freeze-dried and vacuum-dried samples, and it is equivalent to a protective formulation which is in current industrial use. It is known from our previous work on enzymes that the presence of borate can dramatically enhance the protective ability of trehalose. In this work, the addition of trehalose-borate to bacterial concentrate greatly improves the recovery of viable cells after storage. This improvement was seen in freeze-dried samples stored at 37 degrees C as well as for vacuum-dried samples held at room temperature. A tailored buffering strategy was tested to counteract the high pH resulting from the addition of borate to the mixture. Use of citric or lactic acids in combination with ammonium hydroxide gave a protectant solution with high pH (resulting in effective crosslinking between trehalose and borate) but a dry product with reduced pH upon rehydration (conducive to cell survival). These results raise exciting possibilities for protection of more labile prokaryotic species as well as simple eukaryotes.

Ammonium Hydroxide↗