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A vertical cone mixer has been used to mix a single active component, fenfluramine hydrochloride, with a number of diluents used for production batch-scale tablet preparation. The mixing operation was followed by the analysis of fenfluramine hydrochloride in a number of samples equivalent to the final tablet size. The results may be suitably analysed by treating the diluent materials as a single component in a binary mixture.

The rate of neutralization of acid by spray-dried products bound with gum arabic, gelatin, polyvinyl alcohol, carboxymethylcellulose, methylcellulose, and polyvinylpyrrolidone was investigated to evaluate antacid and timed-release properties. A double-layer model was assumed to analyze the neutralization velocity. Diffusion and the reaction layers at the interface between solid and liquid were considered, and an acid neutralization rate equation was developed. The mass transfer coefficient and reaction rate constant for acid neutralization were determined to be 9.3 × 10−3−7.0 × 10−2 cm sec−1 and 400–500 cm3 sec−1, respectively. The percentage of spray-dried particles coated with binder was 80% for carboxymethylcellulose and 48–65% for gelatin, methylcellulose, and polyvinyl alcohol products. Gum arabic and polyvinylpyrrolidone products proved to be only agglomerated. Tableting the powdered spray-dried products increased the proportion of encapsulated material from 48–83 to 70–98%, and their timed-release capacity was greater than that prior to tableting.

Tests were developed to evaluate the following tableting characteristics of detergent tablets: compressive strength, impact strength, and break-up rate. The reproducibility of these tests was determined. Criteria and requirements for satisfactory commercial tablets were established.

The instrumented rotary tablet machines (IRTM’s) previously described have been used to study many phases of the tableting process. The performance of rotary tablet machines with respect to compressional force generated at various settings of the machine controls and to the tablets produced was analyzed and graphically described. Additional studies established the specific relationships between the dimensions and physical properties of the tablets and the compressional forces used to prepare them for a number of different tableting mixtures. These findings are compared with similar relationships obtained by others who used instrumented single punch tablet presses, specialized “static” compression methods, or empirical methods of measuring compressional force. In most cases the results obtained for rotary machines were similar to those previously reported, but in a few instances contradictory behaviors were observed. It was concluded that the excessive amount of punch-to-punch and cycle-to-cycle variation in compressional and ejectional forces that was unexpectedly found to exist for rotary tablet machines is primarily due to unequal filling of the individual dies with stock. Some applications where IRTM's were used to investigate typical tablet development and production problems are described.

The effect of the granulation and tableting processes on the dissolution rate of phenobarbital, sodium phenobarbital, phenacetin, and prednisone in human gastric juice has been investigated. A study has also been made on the influence of the particle size of the active ingredient and the effect of different binders on the dissolution rate of phenobarbital.

The necessity for a comprehensive quality control program for tableting tools is discussed and the establishment of tool specifications and inspection facilities are described. Several experiments are presented leading to the evaluation of steels, tool shapes, tolerances, granulations, and tool maintenance on the effective life span of the tableting tools.

The production of compressed materials, such as tablets, is often jeopadized by capping. Special phenomenalistic studies were made of the factors of capping, and the method to prevent capping was devised.Using a tableting machine and a compression testing instrument, the capping tendency under various compressing and ejecting conditions was studied. As the result of the investigation the following conclusion was reached. Capping occurs mainly within the range of about 3mm from the starting point of ejection. Application of suitable pressure within that range is effective for prevention of capping, and the magnitude of pressure is calculated from the quantity of the wall friction between the compressed material and the die in the ejecting process.

By converting detailed nitrogen desorption isotherm data to pore-volume distributions, as many as three different pore systems have been distinguished in a single calcined catalyst. Dehydration pores are observed to be formed by the loss of water from larger crystals of alumina hydrates, either alumina trihydrates or alumina monohydrate (boehmite). These pores are small and sensitive to sintering conditions. Interparticle pores are found which appear to be developed from the packing of the ultimate particles. The volume and sizes of the interparticle pores are shown in some cases to be directly dependent on the size of the ultimate particles. When the particles are small (about 35 A) the interparticle pore size is sensitive to the method of drying of the alumina hydrate. The size and volume of pores formed by larger particles (greater than 100 A) can be affected by extrusion and tableting techniques.

Instrumentation for evaluating the dustiness of tableting materials is reported. The sample is dropped into a dust chamber where a controlled flow of air carries the resulting dust particles through a beam of light. The scattered light is received by a photo-detcctor which converts light pulses into electrical pulses. The instrumentation was precalibrated in particle-size ranges of 0.5-10, 11–50, and > 50 μ, and the number of particles in each size range is displayed on a digital counter. The particle size refers to the equivalent diameter of the dust particle that generates the same electrical response in the photodetector as the reference particle used to calibrate the instrumentation. Eleven commonly used tableting aids were classified into three categories based on their relative dustiness. Data obtained with the dust counter were shown to correlate with the dustiness resulting from the bulk handling of larger quantities of materials.

A program of industry-wide standardization of punch and die specifications has been proposed by the Industrial Pharmaceutical Technology Section of the Academy of Pharmaceutical Sciences. The standards presented can be employed as guides for purchasing, incoming inspection, and manufacturing use of these tools. An outline for an incoming inspection program for tableting tools is also described.

Tableting properties of a directly compressible starch are investigated. This starch appears to have many advantages over starch USP with respect to fluidity and compressibility and as such would be useful in direct compression. In addition, compressible starch gives results comparable to USP starch in terms of disintegration time and dissolution rate when used at equivalent levels. The high moisture content of compressible starch does not affect the stability of aspirin when compressed together. Amylose is shown to be the effective component of starch in terms of its disintegrant effect. Doubt is cast on the role of starch grain swelling in tablet disintegration.

The objective of this study was to develop a sustained release matrix tablet of aceclofenac using hydroxypropyl methylcellulose (HPMC K15M and HPMC K100M CR) in various proportions as release controlling factor by direct compression method. The powders for tableting were evaluated for angle of repose, loose bulk density, tapped bulk density, compressibility index, total porosity and drug content etc. The tablets were subjected to thickness, weight variation test, drug content, hardness, friability and in vitro release studies. The in vitro dissolution study was carried out for 24 hours using United States Pharmacopoeia (USP) 22 paddle-type dissolution apparatus in phosphate buffer (pH 7.4). The granules showed satisfactory flow properties, compressibility index and drug content etc. All the tablets complied with pharmacopoeial specifications. The results of dissolution studies indicated that the formulations F-2 and F-3 could extend the drug release up to 24 hours. By comparing the dissolution profiles with the marketed product, it revealed that the formulations exhibited similar drug release profile. From this study, a decrease in release kinetics of the drug was observed when the polymer concentration was increased. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport, which was only dependent on the type and amount of polymer used. The drug release followed both diffusion and erosion mechanism in all cases. The drug release from these formulations was satisfactory after 3 months storage in 40°C and 75% RH. Besides, this study explored the optimum concentration and effect of polymer(s) on acelofenac release pattern from the tablet matrix for 24 hour period. Key words: Aceclofenac; sustained release; hydrophillic matrix; HPMC; direct compression. DOI: 10.3329/dujps.v8i1.5332 Dhaka Univ. J. Pharm. Sci. 8(1): 23-30, 2009 (June)

Some of the uses of arabogalactan in tableting have been studied. Its action as a binding agent appears to be satisfactory. The stability of a number of tablets made with arabogalactan as the binder have been compared with similar tablets made with acacia. The results are encouraging. Arabogalactan has been partially methylated to give methyl arabogalactan. Arabogalactan acetate has been made by a new procedure.

A new compression fixture was designed for the measurement of the state of binding between a tablet surface and punch face. It was found by the use of this device that the ability of a material to form a"good"or"bad"tablet may be predicted from two factors ; the slipping force of a tablet surface and passive pressure of a lower punch. The results of measurement were also compared with tableting troubles that occur during a large-scale operation.

The development of microcrystalline cellulose has made available to the pharmaceutical industry an extremely valuable tableting agent. It was found that tablets of plain microcrystalline cellulose will tend to soften and swell when exposed to humid conditions, but the effect is reversed upon the removal of increased humidities. Elevated temperatures have no effect on these tablets. Microcrystalline cellulose tablets will disintegrate very slowly in solvents of a relatively low polarity. It is postulated that tablets of this material are a special form of cellulose fibril in which the individual crystallites are held together largely by hydrogen bonding. Tablet disintegration is merely the breaking of the intercrystallite bonds by the disintegrating medium. No significant separation of components was found during the compression of a microcrystalline cellulose-containing formulation. The release of amphetamine sulfate and sodium phenobarbital from tablets containing micro-crystalline cellulose is excellent. Determinations after 10 weeks at various environments indicate that no release problems exist. When the cellulosic compound was used as a dry binder—disintegrator in the direct compression of formulations of ephedrine hydrochloride, quinine sulfate, and a low melting steroid, tablets of outstanding quality were produced.

1. Calcium hydrophosphate, calcium sulfate, basic magnesium carbonate, beet sugar, and glucose are compared as diluents in tableting toxic and strongly aggressive medicinal preparations. 2. It is shown that tableted preparations based on calcium hydrophosphate, calcium sulfate and basic magnesium carbonate are superior in quality and have more effect on the compacting conditions than those based on beet sugar and glucose. 3. It is shown that calcium hydrophosphate, calcium sulfate, and basic magnesium carbonate can be used as diluents in tableting promedol, codeine, ethylmorphine hydrochloride, diabazol, phenobarbital, papaverine hydrochloride, caffeine-sodium benzoate, and also mixtures containing phenobarbital and papaverine hydrochloride.

A study was undertaken to determine the effect of the tableting procedure on starch grain swelling and tablet disintegration. The swelling of damaged starch grains in simulated gastric fluid USP is demonstrated. Submersion of starch samples that had been ball milled from 10 to 48 hr. produced increases in grain diameters of 40 to 80 percent. Damage to the grains resulting from compression of pure cornstarch is shown to be insignificant. The effect of compressional force and hardness of tablet ingredients was examined and in each formulation the starch grain damage increased with compressional force. There was no correlation between degree of starch grain damage and hardness of the tablet ingredients. It appeared that the crystalline form of the ingredient may have exerted a greater influence on starch damage than the hardness. There was no correlation between starch damage and stress produced by elastic recovery of the tablet. Contrary to what might be expected, there was an inverse relation between the amount of stress and the degree of starch grain damage for all of the formulations except aspirin. There was no evident relationship demonstrated between disintegration time and starch grain damage. Outside of compressional force, the inherent effect of the tablet ingredient was the only factor that appeared to affect disintegration. The long-accepted swelling mechanism of starch as a tablet disintegrant was not demonstrated in this study. The results of the investigation revealed no measurable correlations between starch grain damage and disintegration or between starch swelling and compressional force.

Two conventional rotary tablet compressing machines, the Stokes models 540–35 and BB2–27, have been instrumented to measure both compressional and ejectional forces. This was accomplished by attaching strain gauges to key components of the presses and displaying the electrical outputs of the strain gauges on a dual-beam oscilloscope fitted with a camera. The compressional and ejectional forces developed during the tableting operation are thus obtained under dynamic conditions. The design, construction, and performance of these instrumented rotary tablet machines (IRTM) are described and illustrated.

The deaggregation rates of a relatively insoluble benzoic acid derivative and its soluble sodium salt were studied. Based on the postulate that the deaggregation rate follows a first-order process, equations were developed to measure the rates quantitatively. A spectrophotometric procedure, which is simple and convenient for use routinely, is described. The surface area of the aggregates at the final state was estimated from a correlation between the absorbance measurements and the surface area determined with a Coulter counter. It was seen that encapsulating or tableting these compounds decreased the deaggregation rates. The addition of a nonionic polyol surfactant or the sodium salt of polymerized alkyl naphthalene sulfonic acid enhanced the rates. A relationship between the deaggregation rate and rate of solution of the acid in simulated intestinal fluid T.S. (U.S.P. XVI) is demonstrated. The biopharmaceutical significance of the deaggregation rate is discussed.

Various factors relating to the use of vacuum tumble dryers for the preparation of tablet granulations were studied.A dryer was employed (the 1-cu.ft.solids processor) which has a working capacity of 15-18 kg.for most pharmaceutical granulations.A typical process involves the wetting of the substrate with a drug solution and then drying at a predetermined temperature and vacuum.It was found that uniform drug distribution for low-dose tablet formulations could be obtained.Drying rates were determined for spray-dried lactose and dicalcium phosphate dihydrate at two temperatures and three tumbling speeds.Drying times varied from 35 to 60 min.A series of modified direct compression formulations was studied in which microcrystalline cellulose was used at two levels; two lubricants, calcium stearate and stearic acid, were employed; and lubricant addition was carried out by two methods, internal and external.The effects of these factors on tableting characteristics were monitored by an instrumented tablet machine (Stokes BB-2), and the final physical properties of the tablets were determined.A series of antacid granulations was prepared in which the influence of mixing time and the amount of granulating fluid was varied.The resulting granulations and tablets were characterized as described above.

Studies were conducted to evaluate what changes occurred in the physical properties of compressed tablets as the operation of a rotary tableting machine was varied. Thin large-diameter tablets showed a capping tendency that was not apparent in smaller-diameter or thicker tablets. The crushing strength of tablets stored at 71 per cent R.H. for 28 days was unchanged, but the tablets became more friable. Increasing the compressional speed reduced the crushing strength and increased the capping tendency, but did not affect the friability of compressed tablets. At the higher compressional rates, the tablets showed a greater elastic response than at the slower speeds. Compressing the tablets at various depths in the die had no affect on the physical properties of the compressed tablets.

A method of measuring the fluidity of semifluid powders is described and used to investigate the role of various silica-type glidants in the direct compression of microcrystalline cellulose and a spray-dried lactose/microcrystalline cellulose blend on 2 different tablet presses. All silica-type glidants were found to improve the flow properties of microcrystalline cellulose as reflected in increased tablet weights and decreased weight variations, whereas a reversal of these effects was noted when the filler was the spray-dried lactose blend. While flow enhancement was attributed to a coating of the filler particles by the glidant, the reverse effect noted in the latter case was attributed in large measure to an increase in the bulk volume of the blend. No difference between the 2 tablet presses was found when the coefficients of variation were tested statistically. A pyrogenic silica and a silico-aluminate were found to be the most effective glidants in terms of over-all performance. These glidants were found effective in concentrations as low as 0.1 per cent by weight when added to microcrystalline cellulose and showed an optimum glidant activity at a concentration of about 0.5 per cent by weight.

1. The conditions were determined for successive saturation of steel KhVG with carbon and boron from powdered materials. Complex diffusion layers consisting of (Fe, M)B needles and a carburized transition layer are formed that reduce the microhardness gradient from the diffusion layer to the base metal as compared with borided steel KhVG after quenching and low-temperature tempering. 2. Operating tests of dies in tableting machines showed that the cyclic strength of carboborided dies is 200–250% that of borided dies. The treatment is recommended for parts of stamping and pressing machines.

Preproportioned quantities of dental cement powders may be useful in obtaining correct powder: liquid ratios. Some dental cement powders have been investigated with regard to the feasibility of converting them into tablets to achieve this aim. The results indicate that with some powders it may be possible to achieve this, without complex reformulation.

In an evaluation of the antistatic properties of tablet lubricants, data were obtained to indicate that magnesium stearate, polyethylene glycol 4000, sodium lauryl sulfate, and talc have the ability to lower the accumulation of static charges resulting from the flow of material through a tablet hopper. The antistatic property of these lubricants was demonstrated with different highly static materials. The antistatic effectiveness of the lubricant is decreased with lower concentrations of lubricant.

1. The limiting wear at the die hole walls in tableting a citramon preparation of given particle size distribution was equal to 20–25μ. 2. The wear of dies made from grade Kh12M steel was less by a factor of 3 and 2.5 respectively than that of grades 20Kh and KhVG steels. 3. The optimal diametral clearances between the punch caps and the dies for a diameter of 12 mm can be taken as 30–40μ, and between the punch stems and the dies 10–30μ (in order to reduce the spilling of powder). 4. The wear resistence of punches made from the same material as the dies is approximately double that of the dies. 5. The wear of the punch caps depends on the die material, while the wear of the punch stems is independent of the die material.

In order to study the problem of granulation flow in tableting as it is related to interparticle friction, the response angle of a sulfathiazole granulation was studied as a function of average particle size, presence of lubricants, and admixture of fines.In general, the repose angle increased with decreasing particle size.Talc added to granules in small concentrations decreased the repose angle but tended to increase the angle at higher concentrations.Magnesium stearate had little or no effect on the repose angle of the granulation samples studied.Addition of fines to coarse granules caused a striking increase in repose angle.

Films of acacia, gelatin, methylhydroxyethyl cellulose, polyvinylpyrrolidone (PVP) and starch have been prepared with moisture levels of 2·0 to 20·0% w/w obtained by equilibration at relative humidities from 0 to 90%. Tensile strengths of 60 mm × 2 mm strips of these films have been determined by stressing to failure at a constant rate of 6·6 times 10−5 ms−1 in a tensile strength apparatus. From the stress-strain curves the modulus of elasticity, yield strength and the work done in breaking unit cross-sectional area of the films have been calculated. This has given an indication of the binders’ mechanical behaviour over the range of moisture contents likely to be encountered in tableting.

The effect of magnesium lauryl sulfate on tablet ejection force and filler compressibility was evaluated and compared to magnesium stearate in four direct compression fillers (micro- crystalline cellulose, compressible starch, spray-dried lactose, and direct compression sucrose) and a typical wet granulation (terra alba) using a rotary tablet press instrumented to monitor ejection and compression forces. Generally, higher concentrations of magnesium lauryl sulfate were required to produce ejection forces similar to those obtained with magnesium stearate. However, batches employing magnesium stearate were generally less compressible than batches employing magnesium lauryl sulfate at levels sufficient to produce similar or lower ejection forces.

Lactose USP (beadlets) and dextrose (PAF 2011) have been evaluated and compared with two commonly used agents for direct compression—spray-dried lactose USP and anhydrous lactose USP—as to their relative physical properties and stability for tableting by direct compression.The compression characteristics of all four materials were defined with the aid of a rotary tablet machine instrumented with strain gauges.Compression and ejection forces were monitored continuously and correlated with tablet hardness, friability, weight variation, and disintegration times.It was concluded that the two new agents are generally superior to the other materials tested for use as fillers for direct compression.Both exhibited excellent flow and compressional characteristics.Neither agent represents an improvement over the older materials with regard to physical stability.

A preliminary report describing a new tablet granulation is presented. The process for preparing tablets using this granulation is described. Potential advantages resulting from its use are discussed in the following areas: (a) ease of manufacture, (b) improvement of stability, (c) utilization of pigment colorants, (d) admixture of incompatible chemicals, (e) tableting of thermolabile and moisture-labile materials, and (f) improvement in tablet physical properties.

A study of tableting tool life records, accumulated over a period of 8 years, has served to develop and define relationships between tool performance and the many operating variables that exist in routine tablet production. The effects of these numerous factors on punch and die life have led to conclusions involving techniques for extending tool usability. Outstanding among these are narrowing of working tolerances for tools and extension of product runs on individual machines rather than frequent interchange of machine and tools.

The literature reports on the subject of interunit dosage and weight variations of tablets indicate that past studies were mainly concerned with analyzing the finished product to detect gross departures from the desired quality. These studies, however, were cognizant of the several stages of manufacture before the compression step could contribute to the end tablet variability. In this investigation, the variability in several stages of tablet manufacturing (dry mixing, granulating, lubricating, and tableting) was evaluated for a particular tablet formulation. The importance of employing correct sampling procedures to obtain random samples to be used for the accurate estimation of the sources of variability and product uniformity is illustrated. The relationship that exists between tablet weights and drug concentration was determined. Since systematic sampling is commonly employed in the in-process control of tableting operations, the information that can be gained from this type of sampling procedure and random sampling is presented and discussed.

Microcrystalline cellulose was exposed to the atmosphere of the tableting room. It was found that this exposed material did not tablet as well as material taken from the original, sealed container. Heating of the exposed material improved its tableting characteristics as was shown by increases in the weight and hardness of the tablets produced. Lubrication of the exposed material served to increase tablet weight, but this was accompanied by a decrease in the hardness of the tablets. The combination of heat and lubrication also gave heavier tablets, but again at a sacrifice in hardness.