FLUIDIZATION BEHAVIOR OF STICKY PARTICLES

To obtain fundamental Information on the fluidization behavior of sticky particles, a visually observable fluidized bed, which can be operated under conditions in which agglomeration of the bed materials occurs, was designed and constructed. Polyethylene particles with a softening temperature of 117.2^°C and melting temperature of 124.4^°C, in sizes from 850 to 50 μm, were chosen as the bed material. Two types of fluidizing gas distributors were used: a porous plate and a porous plate with an independently fed jet at the center. The agglomeration rate was measured at different jet and bed temperatures, particle sizes, and residence times in the fluidized bed.

The amount of agglomerates generated increased linearly with residence time and increased exponentially with either auxiliary air or jet air temperature. The agglomerates were formed from the whole range of particle sizes, but fine particles enhanced the agglomeration rate. A set of operating conditions must be properly chosen; otherwise, excessive agglomeration can lead to catastrophic sintering and defluidization.     

ULTRA-PRECISION DIAMOND MACHINING OF ADVANCED TECHNOLOGY COMPONENTS

The design, development, and application of ultra-precision CNC machines for

the single point diamond turning of non-conventional metal optical components (Al, Ge, etc. )

the diamond grinding of ferrite and, other ceramic components for magnetic disc flying heads, etc.

is described. In both cases, tolerances on workpieces in the order of ± 0·1 μm were specified and achieved, together with the overriding need to minimize degenerated surface layers, i.e. surface damage.

The effects of chip formation at low depths of cut are discussed. The factors affecting the depths of “damaged layers” formed in turning and grinding are mentioned. Typical advanced technology components for which ultra-precision diamond turning or grinding are widely used are:

Convex mirrors for high output C0₂ laser resonators

X-ray mirrors

infrared lenses in germanium for thermal imaging systems

scanners for laser printers. and drums for copiers

elliptical mirrors for YAG laser beam collectors

spherical bearing surfaces in beryllium, copper, and other materials

ceramics for magnetic read/write heads for computer memory discs

ceramics for cams, cam followers, valve seat inserts, cylinder liners, bearings, cylinder heads, turbo impell ers, etc.

Both single point and diamond grinding for ultraprecision low stress surfaces demand high precision machines that provide

high stiffness of structures and high band-width servo drives;

low rumble, high averaging bearings such as hydrostatic air or oil;

high internal damping of stuctures and drive systems;

multi closed loop control of many parameters, including temperature of coolant and temperature gradients across structures and sub-systems;

coolant delivery to the abrasive/workpiece interface is of critical importance for controlling high surface finish and minimizing surface tresses.

The paper gives examples of how these problems are satisfied in today's state of the art ultra-precision CNC machine tools.     

Investigation of Prolonged Drug Release from Matrix Formulations of Chitosan

A hydrocolloidal matrix system containing complexes of chitosan was investigated for preparation of sustained release tablets and examined in-vitro.

Theophylline tablets using chitosan as a sustained release base were evaluated. It was found that when chitosan is used in a concentration of more than 50% of tablet weight, an insoluble non-erosion type matrix was formed. Tablets prepared with a chitosan concentration of less than 33% were fast releasing.

Chitosan used in a concentration of about 10% acted as a disintegrant and the drug was dissolved within an hour.

Citric acid slowed down the release rates of chitosan based theophylline tablets. Theophylline tablets using carbomer-934P as a sustained release base were evaluated. Carbomer-934P in lower concentrations forms an erosion type matrix. In order to produce a twenty-four (24) hour sustained release tablet, more than 10% concentration of carbomer-934P is needed. Combination with chitosan and carbomer-934P produced slower releasing tablets.

A hydrocolloidal erosion type matrix was formulated using chitosan, carbomer-934Pand citric acid. Only 10% of chitosan was needed to prepare theophylline sustained release tablets in these mixtures.

The dose dumping potential of chitosan tablets due to rapid disintegration in alkaline media was eliminated by preparing hydrated erosion type matrix systems.     

Crystal Engineering and Particle Design for the Powder Compaction Process

The historical background to the subject of crystal engineering of pharmaceuticals is briefly reviewed with reference to materials as diverse as insulin and direct compression tablet excipients. In the light of the limited scientific and practical information available on the topic two questions are posed -

Is it possible to prepare 'designer' materials with preferred processing, specifically compressive, properties giving optimised product characteristics?

How can such materials be efficiently manufactured?

In order to consider these questions, several important elements of data-base requirements are regarded as essential. These include knowledge of the crystalline phases of pharmaceutical solids, full understanding of the fundamental mechanical constants and moduli of particulate solids, and the relationships describing the influence of crystallographic structure on the mechanical properties of crystals and powders. At the same time the effects of preparation, pretreatment and processing effects on crystal structure, crystallinity and thermodynamic properties of powdered solids must be established.

The topics of material based compaction problems, property groupings of pharmaceutical powders with particular emphasis on crystal structure and mechanical properties are discussed. The review then considers recent and current research work examining the compaction behaviour of modified or engineered materials, prepared using alternative crystallisation conditions and the incorporation of low level additives. Specific examples include modern direct compression excipients, 'spherical' drug particle production and high purity lubricant (magnesium stearate) powders.

In conclusion, the future potential of the concepts of crystal engineering and particle design is considered in terms of predicting mechanical and processing properties from fundamental molecular and structural information.     

EFFECT OF SURFACTANT ADDITION ON THE MICROSTRUCTURE OF COAL FILTER CAKES

Currently, water removal from fine coal fractions is affected by vacuum filtration of a coal slurry followed by thermal drying. Due to high operating costs and the potentially hazardous nature of the drying operation, alternate methods are sought.

This work investigated the change of filter cake microstructure resulting from one such method, namely, surfactant addition to the coal slurry. By impregnating a coal filter cake with an epoxy resin, micrographic analysis of the cake structure could be made by using an image analyzer with the aid of quantitative stereology. This analysis provided a particle and pore size distribution of the filter cake which is fundamental to the understanding of the dewatering mechanism.

Three surfactants were investigated in this work: non-ionic Triton X-114, anionic Aerosol-OT, and cationic dodecyl pyrindinium chloride. The behavior of Triton X-114 and DPC was similar; they both enhanced dewatering by reducing the amount of particle segregation while increasing the pore size of the cake. Conversely, Aerosol-OT, while exhibiting enhanced dewatering characteristics, did not significantly alter the filter cake structure. At low concentrations all three surfactants exhibited little change in particle and pore size distributions when compared to a filter cake formed at the same conditions without surfactant.

Additionally, a linear relationship was shown to exist between the volume-surface mean diameters of the particles and that of the pores. Similar relationships are also presented for the geometric mean diameter and the geometric deviation. The best correlation between particles and pores was obtained from coal cakes formed with Aerosol-OT.     

Statistical Optimization of a Controlled Release Formulation Obtained by a Double Compression Process: Application of an Hadamard Matrix and a Factorial Design

A formulation containing an antiinflammatory agent (diclofenac sodium), two inert matrices (ethylcellulose and polyvinyl chloride) and two lubricants (magnesium stearate and talc) was optimized by a double compression process

In a first stage, preliminary trials were performed in order to study the effect of lubricants added before and after precompression

An Hadamard matrix H(8) was applied to estimate the main effects of four parameters: applied force at the upper punch (UPF) during precompression, particle size range after grinding, UPF during the final compression and concentration of ethylcellulose added before the final compression

Following the Hadamard matrix, a factorial design 2² was built. The complete linear models were fitted by regression for each response reflecting the compression behaviour and dissolution kinetics

In an optimal point, the validation was carried out with the area under the dissolution curve, being the major response to be optimized

The dissolution curves were well fitted by the Weibull distribution     

Granulation in a Fluidized Bed II Effect of Binder Amount on the Final Granules

There are many parameters affecting the properties of the final granules prepared in a fluidized bed. In this study one of the product parameters, quantity of the binder, has been studied for its effect on the final granule size, size distribution and friability

Determination of granule size change as a function of binder quantity leaded us to study the growth mechanisms during fluidized bed granulation. Two mechanisms are suggested;

1) Snowballing of primary granules (nuclei)

2) Agglomeration of primary granules

It has been shown that there is a critical amount of binder at which the formation of the primary granules comes to an end if more binder is added to the system. Then granule growth occurs by agglomeration of the primary granules. The physical properties of the granules formed before and after this critical binder concentration varies significantly     

Liposomes for Drug Delivery to the Respiratory Tract

This paper provides a review of the current literature pertaining to the pulmonary delivery of liposomes.

The technological aspects of delivering liposomes to the lung are discussed, including the characterization of liposome-containing aerosols and the potential advantages and disadvantages of the various methods which have been employed for their generation.

Studies have indicated that liposomes can be effectively deposited in the human respiratory tract, wherein they may remain for prolonged periods. A prolonged retention in the airways may markedly alter the pharmacokinetics of liposome associated materials; increasing local concentrations, whilst decreasing levels at sites distant from the lung. The future potential for such systems is discussed, including the possibilities for selective drug delivery to specific cell populations within the lung.     

Effect of Flowing Adjuvants on the Homogeneity and the Kinetics of Mixing of Low Dosage Cohesive Powder Mixtures

One of the major problems encountered in powder mixing, depending on the properties of the constituents of the mix is the inability of low-power mixers to break down powder agglomerates

The effects of the addition of two flowing ad juvants (colloidal Aluminium oxide and Aerosil-200^R) on the homogeneity of cohesive powder mixtures and on the kinetics of mixing, were investigated

It was demonstrated that colloidal Aluminium oxide increases the degree of homogeneity of a 1 % Triamteren-200 mesh lactose mixture blended in a Turbula T2 C mixer, when an appropriate concentration of the adjuvant, corresponding to that which produces the best flowing properties of the excipient was used. Aerosil-200^R did not enhance the homogeneity of the mix     

A COMPARISON OF TWO NaCl TEST SYSTEMS USED FOR MEASURING FILTER EFFICIENCY

The filter efficiency of materials to be used in respiratory protective devices is commonly measured by using a solid NaCl particle challenge and a flame ionization detector. The Moore's BS 4400 Bench Rig is an example of such equipment.

Recently, TSI, Inc. introduced their Model 8110. This system also produces a NaCl particle challenge. It uses a laser diode detector.

The filter efficiencies of two different filter materials were determined in a comparative study utilizing several Moore's and TSI systems. The results indicate that the two test systems are relatable and that the between-machine consistency of the Model 8110 is better than the Moore's system.     

EFFECT OF CLAY CONTENT ON SURFACE CHARACTERISTICS OF COAL GROUND UNDER DIFFERENT CONDITIONS

The surface characteristics of a coal with a kaol in content of 7% have been studied.

The coal has been either wet or dry ground, with and without an additive. All the products have been examined by XPS and IR spectrometry.

The results show that the wet and dry grinding lead to different surface content of the clay species, while the additive seems to have negligible effect. Wet grinding leads to a concentration of kaolin on the coal surface that is 3 times higher than in the case of the dry ground sample and 7 times higher than in the bulk.     

Scheduling Policies for Automatic Warehousing Systems: Simulation Results

This paper examines and extends previous analytical work on the scheduling of stacker cranes in automatic warehousing systems. In particular, the following are examined by means of a computer simulation:

(1) The performance of the closest-open-location rule compared to random storage assignment;

(2) The dynamic behavior of the system under stochastic conditions, using various crane and rack utilization levels;

(3) The actual versus predicted reduction in crane travel time due to improved scheduling rules;

(4) The effect of imperfect information concerning the length of stay of an incoming pallet on system performance.

The results of our experiments provide evidence in support of the proposed analytical models. Most important, the experiments demonstrate the value of previously-proposed scheduling rules in a dynamic, stochastic environment operating with imperfect information.     

ELECTROCHEMICAL METALLIZING OF ADVANCED MATERIALS

Electrochemical metallizing provides sound metallurgical coatings for maintenance and production applications. The technique involves tankless electroplating, using a brush-on procedure.

Maintenance applications involve resizing, restoring, rebuilding or resurfacing worn, damaged, corroded, eroded or overmachined metal components. This paper deals with special production applications. The title may be a misnomer, since the paper deals with advanced materials, but also covers special unique applications and infrequently used metals and alloys.

For experimenting with new advanced materials, electrochemical metallizing is invaluable. Manually operated, not requiring large or expensive equipment, enabling rapid controlled deposition of numerous metals, alloys and composites, the system provides a low-cost experimental start-up procedure.

Advanced materials covered are primarily metal composites--nickel with a codeposited fluorinated carbon and a nickel-silicon deposit. The first has a decomposition temperature of 850° to 1000°F (460° to 535°C) and a very low friction coefficient. This makes it useful for high temperatures, low sticking and high wear applications, sometimes replacing Teflon or chromium. The second has a Vickers hardness of HV725 (at 100 grams load) and interesting high hardness applications. Also noted are nickel-silicon carbide, nickel-alumina-silicon dioxide and cobalt composites.

Special application deposits exist for preventing galling; improving brazeability; improved bonding of rubber or plastic to aluminum alloys; aluminum hard coatings; repairing electroless nickel; and light-absorbent surfaces.

Finally, the paper deals with electrochemical metallizing materials infrequently used, e.g. antimony, arsenic, bismuth, gallium, indium, palladium, rhenium, ruthenium, nickel-zinc, nickel-phosphorous, nickel-tungsten and tin-indium.     

Validation of solid dosage forms the FDA view

In May 1987 the United States Food and Drug Administration published the final version of a guideline for process validation for pharmaceutical manufacturing. The document incorporated the comments from the pharmaceutical industry gathered after the publication of three draft versions in 1983, 1984 and 1986.

The presentation will cover the current definition of process validation as well as terms such as “worse case” and “installation qualification”.

The stages of process validation will be discussed including the written plan (protocol): records to be maintained; suitability of raw materials; equipment performance qualification; the number of runs required; and acceptance criteria.

Specifics for solid dosage forms will be presented along with details on batch record in instructions and establishment of acceptable range limits.

Circumstances and requirements for revalidation will be discussed as well as the validation of current finished dosage forms by retrospective validation.     

ELECTROSTATIC SEPARATION OF ULTRAFINELY GROUND LOW-RANK COALS

Low-rank coals have an as mined ash content in the range of 10 to 30 per cent. It has been well documented that ash in these coals occurs as organically bound inorganics and as finely divided minerals which are dispersed throughout the coal structure. Consequently, burning some of these coals in conventional power plants may result in slagging of furnace walls and added costs for pollution abatement equipment.

Coal cleaning by dry methods has special appeal where coal is utilized as dry solids since moisture removal after treatment and water pollution control are not required. Utilizing the differences in the electrostatic properties of finely ground coal and minerals is not commercially available but is one dry method with potential for further development. This method depends on the deflection of small particles by an electrical field with the positively charged particles moving in the direction of the field while the negatively charged particles move in the opposite direction.

A key factor in this process is the development of a differential charge between the ash-rich and the carbon-rich particles. Triboelectrification and corona discharge methods have been combined in this study to accomplish this differential charging phenomenon. Both a theoretical study and an experimental investigation of the process were performed and are reported here.     

Role of the mixing conditions and composition of galvanic sludges on the inertization process in clay-based ceramics

Hydroxide-metal sludges from electroplating industry are a potential source of environmental contamination due to their high content of heavy metals. The incorporation of these residues in a ceramic matrix can be a promising way to suppress the harmful effect of metals normally present in those sludges. This work reports the role of the mixing time between the waste and ceramic materials and of the calcination step on the fixing level of several metal-containing species (Al, Zn, Ni, Fe, Ca, Cu, Cr) after sequential leaching in different media (aqueous, acetate and citrate). A strong and/or long mixing process will promote the deagglomeration of the coarser agglomerates and then will increase the reactivity of remaining grains towards the ceramic material during the calcination. As a consequence, inertization is improved for fired samples. With non-calcined samples leaching increases as a result of increasing dispersability/availability of species.     

Disintegrants in Solid Dosage Forms

The dynamic approach to tablet disintegration, which is based on the measurement of the force that develops inside the compact upon water entrance, is basically taken up.

The combined measurements of force development and water uptake, simultaneously effected on the same compact, provide a novel parameter that is proposed to quantify and compare the efficiency of disintegrants.

The new parameter, which is based on the “force-equivalent” concept, expresses the capability of a disintegrant of transforming water uptaken into swelling (or disintegrating) force. A few examples, that illustrate the usefulness of this parameter for disintegrant characterization, are given.

In parallel to the quantification of swelling (or disintegrating) efficiency inside compacts, attention is also being paid to the characterization of swelling disintegrants as pure materials.

In particular the case of the so-called limited swelling materials, for which the quantification of intrinsic swelling (particle volume increase in swelling media) is critical, is considered.

The applicability of an instrumental method, which is based on the employment of a Coulter Counter, is discussed alternatively to microscopic methods.

Disintegrant characterization may also be considered in view of new possible exploitations of the swelling properties of polymers in controlling drug release.     

Mathematical Simulation of Controlled Drug Release from Cylindrical Matrix Devices

The general mathematical model for controlled drug release from the cylindrical matrix device was developed. The system under consideration is composed of an active agent which is dissolved homogeneously in a cylindrical porous matrix device. The method of lines was employed to solve the partial differential equation in the present study.

The effects of hydrodynamic diffusion layer, the rate of spontaneous decay reaction in the device, the height to radius ratio of the device and the porosity distribution in the device on the rate of drug release were investigated by solving the two dimensional diffusion equation under non-steady state conditions.

The results indicated that the release rate may be significantly underevaluated if the data obtained in the in vitro studies under a poor mixing condition are analyzed mistakenly on the assumption of well mixing condition.

The findings in the present analysis are of practical significance to the design and development of matrix-diffusion type controlled release drug products.     

Solid Dispersion Controlled Release: Effect of Particle Size, Compression Force and Temperature

Solid dispersions are dynamic systems, a careful control of processing variables is required to produce desired physicochemical properties of these systems.

The influence of drug particle size, dispersion temperature and compression force on the release rate of theophylline from solid dispersed system tablets was studied. Theophylline base (micronized and granulate) were embedded into a polymeric mixture of PEG and acrylic/methacrylic esters at controlled temperature and shock cooled. Tablets were made at two compressional forces and drug release was measured spectrophotometrically over a period of fifteen hours.

The release rate of drug dispersed in these insoluble matrices was independent of particle size but not of hardness.

However, variations in ratios of polymeric mixture and dispersion temperature controls the drug release rate from inert matrix more effectively than such factors as drug particle size and lower range of tablet hardness. The fast cooling produced excellent reproducibility of drug content throughout the entire entrapment product. X-ray diffraction study demonstrated no changes in crystalline form of theophylline.