Diffusion of a freely water-soluble drug in aqueous enteric-coated pellets

The effects of filler used in the pellet cores (ie, waxy cornstarch or lactose) and the enteric film coat thickness on the diffusion and dissolution of a freely soluble drug were studied. Two kinds of pellet cores containing riboflavin sodium phosphate as a model drug, microcrystalline cellulose (MCC) as a basic filler, and waxy cornstarch or lactose as a cofiller were film coated (theoretically weight increase 20% or 30%) with an aqueous dispersion of cellulose acetate phthalate (CAP). The diffusion of riboflavin sodium phosphate in aqueous enteric-coated pellets was investigated using noninvasive confocal laser scanning microscopy (CLSM). The in vitro release tests were performed using a USP apparatus I (basket method). Diffusion of drug from the core to the film coat was found to be greater with lactose-containing pellets than with waxy cornstarch-containing pellets. The dissolution test showed that 30% enteric-coated waxy cornstarch pellets had a good acidic resistance in 0.1 N HCl solution for at least 1 hour, while the other enteric pellet formulations failed the test. The waxy cornstarch-containing enteric pellets dissolved at SIF in less than 10 minutes. Confocal images of film-coated pellets showed that waxy cornstarch-containing pellets had less drug dissolved than respective lactose-containing pellets. The observations were further confirmed by measurement of fluorescence intensity of riboflavin sodium phosphate in the film coat. The dissolution test was consistent with the confocal microscopy results. In conclusion, waxy cornstarch as a cofiller in the pellet cores minimizes premature drug diffusion from the core into the film coat layer.     

The peritrophic membrane and faecal pellets of Gammarus lacustris limnaeus Smith

SUMMARY. Gammarus lacustris limnaeus Smith was fed decomposed autumnshed leaves of maple ( Acer saccharum Marsh.) and poplar ( Populus tremuloides Michx.). Faecal pellets were collected at various time intervals after egestion and examined under a light and a scanning electron microscope. Nearly all the faecal pellets collected up to a period of about 7 h after egestion possessed a thin, tightly-fitting peritrophic membrane while those that had been outside the gut of the animal for a longer time lacked a peritrophic membrane. Presumably, after egestion faecal pellets swell because of absorption of water leading to eventual rupture and loss of the membrane. The surface of newly extruded pellets is devoid of microbes and microbes seem to play a very insignificant role in the loss of peritrophic membrane from the pellets.     

Development of polysaccharide gel-coated pellets for oral administration: swelling and release behavior of calcium pectinate gel

The aim of this study was to examine the effect of pellet size, pectin type, pectin concentration, and dissolution medium on the swelling and drug release behavior of spherical pellets containing theophylline and coated with 2 different calcium pectinates, using a multi-level factorial design approach. The spherical pellets were prepared by an extrusion-spheronization method and then coated with calcium pectinate using the diffusion-controlled interfacial complexation technique, which provides a defect-free and uniform coating on solid cores. Theophylline release from the pellets was slowed by the application of the coatings. The time to release 50% of the payload (ie, T50) in an acidic medium was approximately 7 minutes from uncoated small pellets and was 55 minutes after an amidated calcium pectinate coat was applied; a comparable coat on large pellets showed a T50 of 93 minutes. Drug release profiles of dry coated pellets showed a lag time (all less than 20 minutes) when the gel coat hydrated and swelled, followed by a zero-order release. It was found that the release rate was controlled by the pellet size, pectin type, pectin concentration, and dissolution medium.     

A novel computerised image analysis method for the measurement of production of conidia from the aphid pathogenic fungus Erynia neoaphidis

A semi-automated method has been developed for the quantification and measurement of conidia discharged by the aphid pathogen Erynia neoaphidis. This was used to compare conidiation by E. neoaphidis-mycosed pea aphid cadavers, mycelial plugs cut from agar plates, mycelial pellets from shake flasks and by mycelial pellets from different phases of liquid batch fermenter culture. Aphid cadavers discharged significantly more and significantly smaller conidia than plugs or pellets. The volume of conidia discharged was stable over the period of discharge (80 h), but more detailed analysis of the size frequency distribution showed that more very small and very large conidia were discharged after 5 h incubation than after 75 h incubation. Biomass harvested at the end of the exponential growth phase in batch fermenter culture produced significantly more conidia than biomass from any other growth phase. The implications of these findings for the development of production and formulation processes for E. neoaphidis as a biological control agent are discussed.     

Exploring the Potential of A Highly Compressible Microcrystalline Cellulose as Novel Tabletting Excipient in the Compaction of Extended-Release Coated Pellets Containing an Extremely Water-Soluble Model Drug

Compaction of controlled-release coated pellets into tablets is challenging because of the fusion of pellets and the rupturing of coated film. The difficulty in compaction intensifies with the use of extremely water-soluble drugs. Therefore, the present study was conducted to prepare and compact pellets containing pseudoephedrine hydrochloride as an extremely water-soluble model drug. The pellets were produced using an extrusion–spheronization technique. The drug-loaded pellets were coated to extend the drug release up to 12-h employing various polymers, and then they were compressed into tablets using microcrystalline cellulose Ceolus KG-801 as a novel tabletting excipient. The in vitro drug release studies of coated pellets and tablets were undertaken using the USP basket method in dissolution test apparatus I. The amount of drug released was analyzed at a wavelength of 215 nm. The combined coatings of hydroxypropyl methylcellulose and Kollicoat SR-30D yielded 12-h extended-release pellets with drug release independent of pH of dissolution medium following zero-order kinetics. The drug release from the tablets prepared using inert Celous KG-801 granules as tabletting excipient was found faster than that of coated pellets. However, a modification in drug release rate occurred with the incorporation of inert Ceolus KG-801 pellets. The drug dissolution profile from tablets containing 40% w/w each of coated pellets and inert granules along with 20% w/w inert pellets was found to be closely similar to that of coated pellets. Furthermore, the friability, tensile strength, and disintegration time of the tablets were within the USP specifications.     

Iberian Rock Lizards (Lacerta monticola cyreni) Assess Conspecific Information Using Composite Signals from Faecal Pellets

A field and laboratory study was performed to analyse the role of excrement deposited on the substrate in intraspecific communication of the Iberian rock-lizard (Lacerta monticola cyreni). In the field, lizards selected specific sites on rocks to deposit faecal pellets, probably in order to facilitate visual location of pellets by conspecifics. Differential tongue flick rates to chemicals presented on cotton swabs demonstrated that male lizards can detect and discriminate between self-produced scents from faecal pellets and those of other conspecific males. In a subsequent experiment, male lizards were tested in a chamber with two platforms containing a faecal pellet of other male on one side and a control artificial pellet on the opposite side. Males spent significantly less time on the side containing the faecal pellet, suggesting that the decision of where to stay may depend on the presence of faecal pellets. Smaller males moved less than larger males on the experimental side whereas on the control side body size did not influence the proportion of time moving. The ability to discriminate chemicals from faeces, and the effects of faecal pellets on lizard behaviour, suggests that faeces might act as composite signals (visual and chemical) in the intraspecific communication of this lizard.     

Development and Evaluation of a Novel Modified-Release Pellet-Based Tablet System for the Delivery of Loratadine and Pseudoephedrine Hydrochloride as Model Drugs

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion–spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.     

Synchrotron radiation-based microcomputed tomography for three-dimensional growth analysis of Aspergillus niger pellets

Filamentous fungi produce a wide range of relevant biotechnological compounds. The close relationship between fungal morphology and productivity has led to a variety of analytical methods to quantify their macromorphology. Nevertheless, only a µ-computed tomography (µ-CT) based method allows a detailed analysis of the 3D micromorphology of fungal pellets. However, the low sample throughput of a laboratory µ-CT limits the tracking of the micromorphological evolution of a statistically representative number of submerged cultivated fungal pellets over time. To meet this challenge, we applied synchrotron radiation-based X-ray microtomography at the Deutsches Elektronen-Synchrotron [German Electron Synchrotron Research Center], resulting in 19,940 3D analyzed individual fungal pellets that were obtained from 26 sampling points during a 48 h Aspergillus niger submerged batch cultivation. For each of the pellets, we were able to determine micromorphological properties such as number and density of spores, tips, branching points, and hyphae. The computed data allowed us to monitor the growth of submerged cultivated fungal pellets in highly resolved 3D for the first time. The generated morphological database from synchrotron measurements can be used to understand, describe, and model the growth of filamentous fungal cultivations.     

Determination of bacterial cell volume with the Coulter Counter.

Two methods were used to determine mean volumes of cells of Escherichia coli B/rA in both stationary- and exponential-phase cultures, i.e., electronic measurement with a Coulter Counter-Analyzer system and biophysical measurement of the total volume and number of cells in sedimented cell pellets. Within experimental errors, the methods gave the same mean cell volumes.     

Time-Dependent Climate Impact and Energy Efficiency of Internationally Traded Non-torrefied and Torrefied Wood Pellets from Logging Residues

Demand for wood pellets as a renewable alternative to fossil fuels has increased in the past decade. However, production and use of wood pellets involves several operations (biomass extraction, chipping, transport, drying, milling, pelleting, combustion) with negative impacts on e.g. the climate. In this study, the energy efficiency and climate impact of production and use of non-torrefied and torrefied wood pellets were analysed and compared. The wood pellets, produced from logging residues extracted from a boreal coniferous forest stand (Norway spruce (Picea abies (L.) H. Karst)) in northern Sweden, were assumed to be exported and finally used in a power plant. Time-dependent life cycle assessment, expressing the climate impact as global temperature change over time, was used to include annual greenhouse gas fluxes of both fossil and biogenic origin. The results showed that carbon stock changes due to extraction of logging residues contributed most of the warming effect on global temperature. Due to greater demand for raw material, a higher warming impact per gigajoule fuel was obtained for torrefied wood pellets than for non-torrefied wood pellets. However, torrefied wood pellets demonstrated a lower climate impact (per GJ electricity) when advantages such as higher electrical energy efficiency and higher co-firing rate were included. A general conclusion from this study is that replacing coal with non-torrefied or torrefied wood pellets made from logging residues can mitigate climate change. The energy output of these systems was about sevenfold the primary energy input.     

Preparation,Characterization and <Emphasis Type="Italic">In Vitro</Emphasis> / <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Oral Time-Controlled Release Etodolac Pellets

The objective of this study was to prepare time-controlled release etodolac pellets to facilitate drug administration according to the body’s biological rhythm, optimize the drug’s desired effects, and minimize adverse effects. The preparation consisted of three laminal layers from center to outside: the core, the swelling layer, and the insoluble polymer membrane. Factors influenced the core and the coating films were investigated in this study. The core pellets formulated with etodolac, lactose, and sodium carboxymethyl starch (CMS-Na) were prepared by extrusion-spheronization and then coated by a fluidized bed coater. Croscarmellose sodium (CC-Na) was selected as the swelling agent, and ethyl cellulose (EC) as the controlled release layer. The prepared pellets were characterized by scanning electron microscopy and evaluated by a dissolution test and a pharmacokinetic study. Compared with commercial available capsules, pharmacokinetics studies in beagle dogs indicated that the prepared pellets release the drug within a short period of time, immediately after a predetermined lag time. A good correlation between in vitro dissolution and in vivo absorption of the pellets was exhibited in the analysis.     

Influence of operational variables on properties of piroxicam pellets prepared by extrusion-spheronization: A technical note

Summary and Conclusion  The processing conditions has a pronounced effect on the pellet properties. Drying conditions influenced the mean size and the drug release of the pellets. Because of the shrinking of the pellets upon drying at higher temperatures, the pellets also showed increased densities. Freeze drying almost prevented shrinking and thus led to the highest drug release. With an increase in the temperature of drying, the drug release rate decreased. Both spheronization time and spheronization speed affected the shapes of pellets, and the changes in shapes then affected the pellet flow properties. Within the studied range, the circularity of the pellets was affected more by the spheronization time than by the spheronization speed. Drying conditions influenced pellet friability, which decreased with an increase in drying temperature, indicating the formation of more dense structures at higher temperatures. The same result was obtained with spheronization time. With an increase in spheronization time, the friability decreased, because of the formation of more compact masses at higher spheronization time. Mean size was not affected by spheronization time or spheronization speed. Published: March 9, 2007     

Studies of cell pellets: II. Osmotic properties, electroporation, and related phenomena: membrane interactions.

Using the relations between pellet structure and electric properties derived from the preceding paper, the responses of rabbit erythrocyte pellets to osmotic or colloidal-osmotic effects from exchanged supernatants and from electroporation were investigated. Changing the ionic strength of the supernatant, or replacing it with dextran or poly(ethylene glycol) solutions, caused changes of Rp according to the osmotic behavior of the pellet. Rp was high and ohmic before electroporation, but dropped abruptly in the first few microseconds once the transmembrane voltage exceeded the membrane breakdown potential. After the initial drop, Rp increased as a result of the reduction of intercellular space. Rp increased regardless of whether the pellets were formed before or immediately after the pulse, indicating that porated cells experienced a slow colloidal-osmotic swelling. The intercellular or intermembrane distances between cells in a pellet, as a function of osmotic, colloidal-osmotic, and centrifugal pressures used to compress rabbit erythrocyte pellets, were deduced from the Rp measurement. This offered a unique opportunity to measure the intermembrane repulsive force in a disordered system including living cells. Electrohemolysis of pelleted cells was reduced because of limited swelling by the compactness of the pellet. Electrofusion was observed when the applied voltage per pellet membrane exceeded the breakdown voltage. The fusion yield was independent of pulse length greater than 10 microseconds, because after the breakdown of membrane resistance, voltage drop across the pellet became insignificant. Replacing the supernatant with poly(ethylene glycol) or dextran solutions, or coating pellets with unporated cell layers reduced the colloidal-osmotic swelling and hemolysis, but also reduced the electrofusion yield. These manipulations can be explored to increase electroloading and electrofusion efficiencies.     

Decolorization of textile dyeing wastewater by<Emphasis Type="Italic">Phanerochaete chrysosporium</Emphasis>

The potential use of fungal pellets for decolorization of the textile dyeing wastewater was evaluated. The live pellets of the fungus Phanerochaete chrysosporium were found to remove more than 95% of the color of this wastewater within 1 d. The dye-removal capacity was a function of time and was proportional to the agitation rate; the optimum temperature was 30 degrees C. Both live and dead pellets were further examined in a repeated-batch mode for 5 d. The decolorization performance of live pellets remained high and stable for 5 d and they showed twice to thrice higher decolorization capacity than dead pellets.     

DMSP-consuming bacteria associated with the calanoid copepod Acartia tonsa (Dana)

DMSP-consuming bacteria (DCB) were recovered from the body and fecal pellets of the copepod Acartia tonsa (Dana). The most probable number of DCB associated with starved A. tonsa was 9.2x10(2) cells copepod(-1). The abundance of DCB recovered from the copepod body increased to 1.6-2.8x10(4) after the copepod fed on DMSP-containing alga. DCB abundance associated with fecal pellets averaged 1.2x10(4) cells pellet(-1). In enrichment cultures, the DCB grew with a doubling time of 1.1-2.9 days, and consumed DMSP at a rate of 4.5-7.5 fmol cell(-1) day(-1). The apparent DMSP-to-DMS conversion efficiency was 25-41% for DCB from copepod body, and 99% for DCB from fecal pellets. Our study demonstrated that copepods and their fecal pellets may harbour dense populations of DCB, and that the copepod-bacteria coupling represents a novel mechanism for DMSP consumption in the water column.     

Territorial Pheromones of Female Red-backed Salamanders

Pheromones provide an important source of communication during social interactions of caudate amphibians. To further examine their use in territorial defense, we performed a laboratory experiment to test the hypothesis that non-courting female red-backed salamanders (Plethodon cinereus) deposit pheromones in or on fecal pellets, as males are known to do during territorial advertisement. Four conditions were tested: (1) a burrow marked with a female's own pellet vs. a burrow marked by a conspecific female's pellet, (2) own vs. unmarked burrows, (3) conspecific vs. unmarked burrows, and (4) paired unmarked burrows as a control. Females nose-tapped (for olfactory cues) their own and conspecific pellets about equally. However, they spent significantly more time in both threat and submissive behavior toward the conspecific pellets and spent significantly more time in their own marked burrows. We infer that female P. cinereus do deposit pheromones in or on fecal pellets and that these pellets may be used to advertise territories. The behavioral responses of females toward pellets of other females were more aggressive than those of males (in a previous study) toward pellets of other males.     

Pheromonal markers as indicators of parasite load: parasite-mediated behavior in salamanders (Plethodon angusticlavius)

Assessment of parasite load of conspecifics may be important during social interactions such as courtship and aggressive encounters. We used a correlational study to test whether pheromonal markers can be used to assess parasite load of conspecifics, and whether the parasite load of the pheromone receivers affected their responses. We tested the responses of parasitized and nonparasitized Ozark zigzag salamanders, Plethodon angusticlavius, to territorial markers (fecal pellets) from conspecific males. Males and females were simultaneously exposed to fecal pellets placed in front of two artificial burrows located at the opposite ends of their chambers. The treatments were (1) fecal pellet of male with low parasite load versus fecal pellet of male with high parasite load, (2) fecal pellet of male with low parasite load versus control pellet (chemical blank), and (3) fecal pellet of male with high parasite load versus control pellet. Nonparasitized females spent significantly more time near fecal pellets of males with low parasite load in test condition 1, whereas the behavior of parasitized females was not significantly different from random in any test condition. Males responded differently to treatments only in condition 3; males with low parasite loads spent significantly more time near control pellets, whereas males with high parasite loads spent significantly more time near fecal pellets of males with high parasite loads. This study demonstrates that pheromonal markers may be used for assessment of parasite load of conspecifics and that responses by both males and females may be influenced by their own level of infection. Received: 21 January 1999 / Received in revised form: 17 March 2000 / Accepted: 13 November 2000     

Vertical distribution of faecal pellets during FLEX '76

During FLEX '76 (Fladen Ground Experiment), the vertical distribution of faecal pellets was studied at a time station on the Fladen Ground (North Sea). Generally, the faecal pellets showed a clearly-defined maximum above the main thermocline within a depth of 0–30 m. Only in a period of storms was the faeces-maximum lowered to the main thermocline, which occurred at 50–60 m depth. The maximum numbers of the copepodCalanus finmarchicus, the most important producer of faecal pellets, initially occupied the same level as the faeces maximum. However, from the middle of May, theC. finmarchicus population started a diel vertical migration, during which, as a rule, the copepods migrated away from the surface region into deeper waters. On this occasion, the faecal pellet maximum did not break up but remained in the uppermost layer of the water column. The high concentrations of faecal pellets found within the uppermost 30 m of the water column contradict the extremely high sinking rates of faeces reported by various authors. The quotients of the depth-integrated counts of faecal pellets andC. finmarchicus individuals were calculated. The main maximum of faeces per individual occurred in the period between 28 April and 6 May 1976. A second, smaller maximum was documented between 23–28 May 1976. These two maxima coincided with the development of phytoplankton blooms observed at this particular time station.JONSDAP '76 Contribution No. 68.     

Diffusion and reaction within porous packing media: a phenomenological model

A phenomenological model has been developed to describe biomass distribution and substrate depletion in porous diatomaceous earth (DE) pellets colonized by Pseudomonas aeruginosa. The essential features of the model are diffusion, attachment and detachment to/from pore walls of the biomass, diffusion of substrate within the pellet, and external mass transfer of both substrate and biomass in the bulk fluid of a packed bed containing the pellets. A bench-scale reactor filled with DE pellets was inoculated with P. aeruginosa and operated in plug flow without recycle using a feed containing glucose as the limiting nutrient. Steady-state effluent glucose concentrations were measured at various residence times, and biomass distribution within the pellet was measured at the lowest residence time. In the model, microorganism/substrate kinetics and mass transfer characteristics were predicted from the literature. Only the attachment and detachment parameters were treated as unknowns, and were determined by fitting biomass distribution data within the pellets to the mathematical model. The rate-limiting step in substrate conversion was determined to be internal mass transfer resistance; external mass transfer resistance and microbial kinetic limitations were found to be nearly negligible. Only the outer 5% of the pellets contributed to substrate conversion. (c) 1993 Wiley & Sons, Inc.     

Studies of cell pellets: I. Electrical properties and porosity.

Cell pellets formed by centrifugation provided a good system to study the osmotic behavior, electroporation, and interaction between cells. Rabbit erythrocyte pellets were used in this study because they were simpler than nucleated cells to model analytically. Structurally, cell pellets possessed properties of porous solid bodies and gels. Electrically, cell pellets were shown to behave as a parallel set of resistance, Rp, and capacitance, Cp. Information on pellet structures was obtained from electric measurements. The pellet resistance reflected the intercellular conductivity (porosity and gap conductivity), whereas the pellet capacitance depended mostly on membrane capacitance. The pellet resistance was more sensitive to experimental conditions. The intercellular gap distance can be derived from pellet porosity measurements, providing the cell volume and surface area were known. Rp increased and relaxed exponentially with time when centrifugation started and stopped; the cycles were reversible. When supernatants were exchanged with solutions containing hypotonic electrolytes or macromolecules (such as PEG) after the pellets were formed, complicated responses to different colloidal osmotic effects were observed. A transient decrease followed by a large increase of Rp was observed after the application of a porating electric pulse, as expected from a momentary membrane breakdown, followed by a limited colloidal-osmotic swelling of pelleted cells. The equilibrium values of Rp, Cp, pellet porosity, and intercellular distances were measured and calculated as functions of cell number, centrifugation force, and ionic strength of the exchanged supernatant. Thus, the structure and properties of cell pellets can be completely characterized by electrical measurements.