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PubMedDate not supplied

Release of paclitaxel from polylactide-co-glycolide (PLGA) microparticles and discs under irradiation.

Paclitaxel is a promising anti-cancer drug as well as a radiosensitizer for chemotherapy and radiotherapy applications. Because of the poor solubility of paclitaxel in water and most pharmaceutical reagents, it is usually formulated with an adjuvant called Cremophor EL, which causes severe side effects. This work develops new dosage forms of paclitaxel for controlled release application, which do not require the adjuvant and, thus, can avoid its associated side effects. Paclitaxel was encapsulated into the PLGA matrix with various additives such as polyethylene glycol (PEG), isopropyl myristate (IPM) and d-alpha tocopheryl polyethylene glycol (Vitamin E TPGS). These additives were used to enhance the release rate of paclitaxel from the polymer matrix. Spray-drying and an hydraulic press were used to prepare paclitaxel-PLGA microspheres and discs. The microspheres and discs were given different irradiation doses to investigate their effects on the surface morphology (characterized by SEM, AFM and XPS) and in vitro release properties. There seems to be a small effect of the ionizing radiation on various formulations. Although the irradiation did not cause observable changes on the morphology of the polymer matrix, the release rate can be enhanced by a few per cent. It was found that PEG has the highest enhancement effect for release rate among all the additives investigated in this study.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Microencapsulation of L. acidophilus (La-05) and B. lactis (Bb-12) and evaluation of their survival at the pH values of the stomach and in bile.

Microcapsules were prepared using the probiotic microorganisms Lactobacillus acidophilus (La-05) and Bifidobacterium lactis (Bb-12) and the spray drying technique and cellulose acetate phthalate as the wall material. This study evaluated the resistance of these microorganisms to drying at three temperatures and also the in vitro tolerance of the free and microencapsulated form to pH values and bile concentrations similar to those found in the human stomach and intestine. With an air entry temperature of 130 degrees C and exit temperature of 75 degrees C, the number of viable cells of B. lactis was practically unaltered, whereas the population of L. acidophilus was reduced by two logarithmic cycles. B. lactis was more resistant to the drying process than L. acidophilus under all conditions tested. The morphology of the microcapsules was determined by scanning electron microscopy and the microcapsules presented a rounded external surface containing concavities, a continuous wall with no apparent porosity, average size of 22 microm, moisture content varying from 5.3 to 3.2% and water activity between 0.230 and 0.204. After inoculation into HCl solutions with pH values adjusted to 1 and 2, incubated anaerobically at 37 degrees C, and plated after 0, 1 and 2 h of incubation, microcapsules were effective in protecting the microorganisms, while the populations of both free microorganisms were eliminated after only 1 h at the acidic conditions. Microencapsulated B. lactis and L. acidophilus, both free and microencapsulated, were also resistant after 12h to bile solutions.

Bifidobacterium↗
PubMed2004

Microencapsulation of hydrophilic drug substances using biodegradable polyesters. Part II: Implants allowing controlled drug release--a feasibility study using bisphosphonates.

The prolonged delivery of hydrophilic drug salts from hydrophobic polymer carriers at high drug loading is an ambitious goal. Pamidronate disodium salt (APD) containing implants prepared from spray-dried microparticles were investigated using a laboratory ram extruder. An APD-containing polymer matrix consisting of an APD-chitosan implant embedded in the biodegradable polymer D,L-poly(lactide-co-glycolide acid-glucose) (PLG-GLU) was compared with a matrix system with the micronized drug distributed in the PLG-GLU. The APD-chitosan matrix system showed a triphasic release behaviour at loading levels of 6.86 and 15.54% (w/w) over 36 days under in-vitro conditions. At higher loading (31.92%), a drug burst was observed within 6 days due to the formation of pores and channels in the polymeric matrix. In contrast, implants containing the micronized drug showed a more continuous release profile over 48 days up to a loading of 31.78% (w/w). At a drug loading of 46.17% (w/w), a drug burst was observed. Using micronized drug salts and reducing the surface area available for diffusion, parenteral delivery systems for highly water-soluble drug candidates were shown to be technically feasible at high drug loadings.

Adjuvants, Pharmaceutic↗
PubMed2004

Alginate microparticles for Polymyxin B Peyer's patches uptake: microparticles for antibiotic oral administration.

Microparticles with size less than 3 microm, able to be taken up by M cell of Peyer's patches for the drug delivery to the Gut Associated Limphoid Tissue (GALT), were developed in order to improve oral bioavailability of Polymyxin B (PMB). Less than 3 microm alginate microparticles resistant to gastro-intestinal media were prepared by spray-drying technique and cross-linking by calcium ions and chitosan. The cross-linked microparticles were evaluated for PMB content by spectrophotometric method, alginate/PMB interaction by rheological study, cross-linking degree by EDS analysis and PMB activity by microbiological assay. By modulating the polymer cross-linking degree, cationic PMB interacted on alginate chains leading to a proper PMB loading as well as antibiotic retention in gastric environment and sustained delivery in intestinal fluid. Moreover, the procedure resulted suitable for PMB biological activity preservation.

Administration, Oral↗
PubMed2004

Nanoparticle-coated microparticles: preparation and characterization.

The objective of the present work was to design and prepare new nanoparticle-coated drug-loaded inorganic microparticles by spray-drying using diclofenac as drug model. Previous works presented the process to dry drug-loaded polymeric nanoparticles using silicon dioxide as adjuvant, otherwise in the present proposition the drug is associated with the silicon dioxide and unloaded polymeric nanocapsule or nanosphere suspensions were used as organic coating. Eudragit S100 was chosen because of its gastric resistance. The potential application of polymeric colloidal suspensions as nanocoating for microparticles were evaluated in terms of process yields, encapsulation efficiencies, morphologic analyses and in vitro drug release profiles in buffered media (pH 1.2; 5.0 and 7.4). The results showed the technological feasibility of preparing controlled nanoparticle-coated drug-loaded inorganic microparticles. When the diclofenac was employed as a hydrophilic model, in this salt form, the powders prepared in two steps (core previously prepared) showed an adequate gastroresistance by the use of Eudragit S100. The use of diclofenac as a hydrophobic model (acid form) conducted to powders presenting good gastroresistance when the nanocapsules and triacetin were employed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Characteristics of vitamin C encapsulated tripolyphosphate-chitosan microspheres as affected by chitosan molecular weight.

In this paper, the effect of chitosan molecular weight on the characteristics (size, encapsulation efficiency, zeta potential, surface morphology and release rate) of vitamin C encapsulated tripolyphosphate cross-linked chitosan (TPP-chitosan) microspheres. The molecular weight of chitosan had a noticeable influence on the size, encapsulation efficiency, zeta potential, surface morphology and controlled release behaviour of the vitamin C encapsulated TPP-chitosan microspheres. The mean particle size and encapsulation efficiencies of TPP-chitosan microspheres were 3.1, 4.9 and 6.7 microm and 67.25, 60.43 and 52.74% for the microspheres prepared using low, medium and high molecular weight chitosan, respectively. All the TPP-chitosan microspheres (low, medium and high molecular weight) had positive charge on their surface. The zeta potential of the TPP-chitosan microspheres prepared using low, medium and high molecular weight chitosan was 41.25, 40.84 and 39.13 mV, respectively. The particle sizes of TPP-chitosan microspheres increased with increases in chitosan molecular weight. Molecular weight of chitosan did not affect significantly the % yield of TPP-chitosan microspheres prepared by spray-drying. The influence of chitosan molecular weight on the surface morphology of vitamin C encapsulated TPP-chitosan microspheres was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It was observed that, as the molecular weight of chitosan increases, TPP-chitosan microspheres with uniform spherical shape could be obtained. The physical state of vitamin C (amorphous or crystalline) in TPP-chitosan matrix was studied by X-ray diffraction (XRD) and it was found that vitamin C is dispersed at the molecular level (amorphous) in the TPP-chitosan matrix. Release rate of the vitamin C from TPP-chitosan microspheres was significantly affected by the chitosan molecular weight. The release rate decreased with increase in the chitosan molecular weight. The release of vitamin C from TPP-chitosan microspheres followed Fick's law of diffusion.

Ascorbic Acid↗
PubMed2006

New microencapsulation system for ascorbic acid using pea protein concentrate as coat protector.

Microencapsulation is essential to preserve biological activity of ascorbic acid (AA) and pea protein has not been used as a carrier in such processes. This work aimed to produce microparticles by a spray-drying process using pea protein (PPC) as wall material of AA and evaluate the retention of the core by HPLC, overall morphology SEM, size distribution by light scattering and release kinetics. Carboxymethylcellulose (CMC) and blends with maltodextrin (M) were produced for comparative analyses. The yields were compatible with the applied technology and the retention was above 84% for all materials. The PPC microparticles presented irregular and rough surfaces, CMC produced a regular and smooth surface and agglomeration was more intense in microparticles with M. Mean particle diameters were all below 8 microm. The microparticle release rates were lower than those with free AA, being best correlated to the Higuchi kinetic model. These results support the utilization of PPC for microencapsulation of AA.

Aerosols↗
PubMed2006

Biodegradable micro- and nanoparticles as long-term delivery vehicles for gentamicin.

Micro- and nanoparticles of poly(lactide-co-glycolide) (PLGA) loading gentamicin were prepared by a solvent evaporation method with the aim of obtaining appropriate vectors for systemic administration. Microspheres presented mean diameters below 3 microm and nanoparticles showed homogeneous sizes with a diameter of 320 nm. Drug loading was more efficient in the case of microencapsulation. The more hydrophilic copolymers with carboxyl-end groups yielded higher microparticle loadings, reaching encapsulation efficiencies up to 9.2 microg mg(-1) of polymer (502H, 503H or 75:25H). Nanoparticles made of 502H PLGA also achieved an acceptable level of encapsulation (6.2 microg mg(-1)). Particles prepared by using the solvent evaporation method showed no aggregation after hydration, in contrast to the microparticles prepared by spray-drying which showed fast and high auto-aggregation. In vitro release profiles revealed that 503H microspheres showed the highest burst during the first hour, while the most sustained release was for microparticles of 502H copolymer (40% of gentamicin remained in the formulation after 28 days). In summary, microspheres made of 502H, 503H and 75:25H and nanoparticles of 502H showed the best potential properties for systemic use in the treatment of intra-cellular gentamicin-susceptible pathogens.

Agglutination Tests↗
PubMed2006

Preparation and antimicrobial activity of gelatin microparticles containing propolis against oral pathogens.

Gelatin microparticles containing propolis ethanolic extractive solution were prepared by spray-drying technique. Particles with regular morphology, mean diameter ranging of 2.27 microm to 2.48 microm, and good entrapment efficiency for propolis were obtained. The in vitro antimicrobial activity of microparticles was evaluated against microorganisms of oral importance (Enterococcus faecalis, Streptococcus salivarius, Streptococcus sanguinis, Streptococcus mitis, Streptococcus mutans, Streptococcus sobrinus, Candida albicans, and Lactobacillus casei). The utilized techniques were diffusion in agar and determination of minimum inhibitory concentration. The choice of the method to evaluate the antimicrobial activity of microparticles showed be very important. The microparticles displayed activity against all tested strains of similar way to the propolis, showing greater activity against the strains of E. salivarius, S. sanguinis, S. mitis, and C. albicans.

Anti-Infective Agents↗
PubMed2006

The influence of drug-excipient and drug-polymer interactions on butt adhesive strength of ranitidine hydrochloride film-coated tablets.

The influence of fillers and polymeric films on adhesive strength of hydroxypropyl methylcellulose (HPMC) and Eudragit E100 films coated on ranitidine HCl tablets containing either spray-dried rice starch (SDRS) or lactose monohydrate as fillers after storage at 45 degrees C/75% RH for four weeks was investigated by the use of butt adhesion technique. The adhesive strength of film-coated tablets of fillers without drug was found to slightly decrease after storage. In contrast, the adhesive strength of drug-containing film-coated tablets significantly reduced, the degree of which was higher for Eudragit E100 than HPMC. Physicochemical characterization by employing differential scanning calorimetry (DSC) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) revealed that the drug was obviously incompatible with lactose and possibly mild interaction with Eudragit E100 was suggested. The results indicated that the adhesive strength of film-coated tablets would be affected not only by the drug-excipient interaction, but also by the drug-polymeric film interaction.

Adhesiveness↗
PubMed2000

Folates and dairy products: a critical update.

In recent years, folates have come into focus due to their protective role against child birth defects, for example, neural tube defects. In addition, folates may have a protective role to play against coronary heart disease and certain forms of cancer. During the last few years most countries have established increased recommended intakes of folates, for example, between 300-400 microg per day for adults. This review of folates in milk and dairy products compares some recent data based on high pressure liquid chromatography (HPLC) analyses and radioprotein-binding assays, with previous data based on microbiological assays. All three methods show similar ranges for folates in cow's milk, 5-10 microg per 100 g, the variation being due to seasonal variations. Data on folates in fermented milk (buttermilk and yogurt) are also similar for these methods. Different starter cultures, however, might explain some of the variations in folate content and folate forms. Most cheese varieties contain between 10 microg and 40 microg folate per kg, with slightly higher values for whey cheese. Ripened soft cheeses may contain up to 100 microg folate per 100 g. Most previous and recent studies using HPLC indicate that 5-methyl-tetrahydrofolate (5-methyl-THF) is the major folate form in milk, but more studies are needed concerning folate forms in other, especially fermented dairy products. Relatively new data on actual concentrations in different dairy products show folate-binding proteins (FBP) to occur in unprocessed milk, but also in pasteurised milk, spray-dried skim milk powder and whey. In contrast, UHT milk, fermented milk and most cheeses only contain low levels or trace amounts.

Animals↗
PubMed2003

Experimental study of drag resistance using a laboratory scale rotary set-up.

This work covers an experimental study of the drag resistance of different painted surfaces and simulated large-scale irregularities, viz. dry spraying, weld seams, barnacle fouling and paint remains. A laboratory scale rotary set-up was used to determine the drag resistance, and the surface roughness of the samples was determined by means of two different stylus-based methods, one having a 1.6 mm ball stylus (giving the macro-roughness) and the other having a needle type stylus (giving the micro-roughness). It is demonstrated that, in the case of ideal painted surfaces (low macro-roughness), the micro-roughness is much more important than the macro-roughness. On the other hand, the study also indicates that larger scale irregularities have a much greater influence on the drag resistance compared to measurements of the paint system alone.

Friction↗
PubMed1993

Encapsulation of food ingredients.

Microencapsulation is a relatively new technology that is used for protection, stabilization, and slow release of food ingredients. The encapsulating or wall materials used generally consist of starch, starch derivatives, proteins, gums, lipids, or any combination of them. Methods of encapsulation of food ingredients include spray-drying, freeze-drying, fluidized bed-coating, extrusion, cocrystallization, molecular inclusion, and coacervation. This paper reviews techniques for preparation of microencapsulated food ingredients and choices of coating material. Characterization of microcapsules, mechanisms of controlled release, and efficiency of protection/stabilization of encapsulated food ingredients are also presented.

Drug Compounding↗
PubMed2001

Flue gas desulfurization: the state of the art.

Coal-fired electricity-generating plants may use SO2 scrubbers to meet the requirements of Phase II of the Acid Rain SO2 Reduction Program. Additionally, the use of scrubbers can result in reduction of Hg and other emissions from combustion sources. It is timely, therefore, to examine the current status of SO2 scrubbing technologies. This paper presents a comprehensive review of the state of the art in flue gas desulfurization (FGD) technologies for coal-fired boilers. Data on worldwide FGD applications reveal that wet FGD technologies, and specifically wet limestone FGD, have been predominantly selected over other FGD technologies. However, lime spray drying (LSD) is being used at the majority of the plants employing dry FGD technologies. Additional review of the U.S. FGD technology applications that began operation in 1991 through 1995 reveals that FGD processes of choice recently in the United States have been wet limestone FGD, magnesium-enhanced lime (MEL), and LSD. Further, of the wet limestone processes, limestone forced oxidation (LSFO) has been used most often in recent applications. The SO2 removal performance of scrubbers has been reviewed. Data reflect that most wet limestone and LSD installations appear to be capable of approximately 90% SO2 removal. Advanced, state-of-the-art wet scrubbers can provide SO2 removal in excess of 95%. Costs associated with state-of-the-art applications of LSFO, MEL, and LSD technologies have been analyzed with appropriate cost models. Analyses indicate that the capital cost of an LSD system is lower than those of same capacity LSFO and MEL systems, reflective of the relatively less complex hardware used in LSD. Analyses also reflect that, based on total annualized cost and SO2 removal requirements: (1) plants up to approximately 250 MWe in size and firing low- to medium-sulfur coals (i.e., coals with a sulfur content of 2% or lower) may use LSD; and (2) plants larger than 250 MWe and firing medium- to high-sulfur coals (i.e., coals with a sulfur content of 2% or higher) may use either LSFO or MEL.

Air Pollutants↗
PubMed2006

Microcapsules formulated in the enteric coating copolymer Eudragit L100 as delivery systems for oral vaccination against infections by gastrointestinal nematode parasites.

Microcapsules using the copolymer of methacrylic acid (Eudragit L100) were formulated for oral delivery of vaccines against the enteral/parenteral nematode parasite Trichinella spiralis. Antigenic preparations from first stage larvae (L1) of T. spiralis were microencapsulated in Eudragit L100. The microcapsules prepared by the spray drying method were resistant to acid pH, although the antigen was rapidly released under neutral and basic environmental conditions. The native protein conformation and biological activity was preserved in the microcapsules, as assessed by SDS-PAGE and ELISA. When administered to NIH mice, the antigen loaded microcapsules protected against infection by T. spiralis at both the intestinal and muscular levels, the worm burden diminishing by 45.58 and 53.33%, respectively. Furthermore, following administration of the microparticles an increase of the serum IgG1 response, a marker for the Th2 type response, was evident. These results indicate that microcapsules formulated with anionic biocompatible polymers such as Eudragit may be useful for oral vaccination against nematode infections.

Administration, Oral↗
PubMed2006

Ex-vivo evaluation of alginate microparticles for Polymyxin B oral administration.

A crosslinked alginate microparticle system for the targeting to the lymphatic system by Peyer's patches (PP) uptake was designed in order to improve the oral absorption of Polymyxin B (PMB). To verify mucoadhesion and PP uptake, microparticles labelled with fluorescein isothiocyanate (FITC) were prepared by spray-drying technique and crosslinking reactions with calcium ions and chitosan (CS), in vitro characterized and assayed by an ex vivo method. Microparticles showed a size less then 3 microm, an antibiotic loading level of 11.86 +/- 0.70%, w/w, a sustained drug release behaviour in simulated gastro-intestinal (GI) fluids and a preserved biological activity throughout the manufacture. The ex vivo study was performed by a perfusion method on intestinal tracts of just sacrificed adult rats. The recovered samples were analysed by epifluorescence microscope for mucoadhesion and PP uptake and by microbiological analysis for antibiotic activity preservation, providing evidence of mucoadhesion at the level of both PP and non-PP epithelium, uptake by PP and PMB microbiological activity in PP tissue. Furthermore, the study revealed the involvement of transport pathways across villous enterocytes.

Administration, Oral↗
PubMedDate not supplied

Preparation and analgesic activity of Eudragit RS100 microparticles containing diflunisal.

Two different techniques, the quasi-emulsion solvent diffusion method and spray drying that provide polar and nonpolar preparation environments, were used to prepare microspheres from Eudragit RS100 (RS) (acrylic/methacrylic copolymer) incorporating the nonsteroidal anti-inflammatory drug diflunisal. The effects of pH on the preparation medium and drug/polymer ratio on production yield and drug incorporation, as well as on the in vitro drug release at pH 1.2 and 6.8 from tabletted microparticles, were evaluated. The drug-polymer interactions and the effect of diflunisal incorporation in the polymer matrix on drug crystallinity have been evaluated by using differential scanning calorimetry, IR and ultraviolet spectroscopy, x-ray diffraction, and microscopy analysis. A preliminary biological assay confirmed that diflunisal maintains its analgesic activity after intraperitoneal administration to rats.

Acrylic Resins↗
PubMedDate not supplied

Study of gamma-irradiation effects on chitosan microparticles.

Gamma (gamma)-irradiation is finding increasing use in the sterilization of pharmaceutical products. However, irradiation also might affect the performance of drug delivery systems. In this study, the influence of gamma-irradiation on the characteristics of chitosan microparticles was investigated. The diclofenac sodium was incorporated into chitosan microparticles by spray-drying method. The chitosan microparticles (placebo and drug-loaded) were irradiated at doses of 5, 15, and 25 kGy using a (60)Co source. Later, the microparticles were characterized by Fourier transform infrared (FTIR) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and atomic force microscopy. In addition, microparticles also were evaluated for their sizes, drug content, swelling, and drug release behavior. Encapsulation efficiency of irradiated and nonirradiated microparticles was essentially the same. Notably, surface roughness (rms) of placebo microparticles decreased significantly after gamma-irradiation when compared with nonirradiated placebo microparticles. FTIR spectroscopy revealed that gamma-irradiation of chitosan microparticles induced neither cross-linking nor formation of new group in the chitosan matrix. EPR spectroscopy results showed that the gamma rays induced only one kind of free radical in the chitosan matrix. Size, crystallinity, and thermal properties of the chitosan microparticles did not change much after gamma-irradiation. gamma-irradiated microparticles, exhibited a slightly higher drug release rate and low swelling capacity than the nonirradiated microparticles.

Anti-Inflammatory Agents, Non-Steroidal↗