Effect of compression speed on the tensile strength of tablets of binary mixtures containing aspirin.

Mixtures of aspirin with sodium chloride, sucrose, Starch 1500 or Emcompress have been compressed to two maximum upper punch pressures at two compression speeds. Non-linear relationships between tensile strength and composition, and tablet porosity and composition were found in all cases. Tablets of the individual materials compressed at fast speed showed either little change or a reduction in tensile strength when compared with those compressed at slow speed. For mixtures of aspirin with Starch 1500, tablets compressed at fast speed were weaker and more porous than those compressed at slow speed. However, some mixtures of aspirin with sodium chloride, sucrose or Emcompress gave tablets with greater tensile strength and lower porosity when prepared at fast compression speed compared with tablets prepared at slow speed. This behaviour was attributed to the modification of the consolidation behaviour of the aspirin by the second material.

High resolution electron microscopy study of sulphathiazole crystals.

A high resolution electron microscopy study was undertaken on samples of sulphathiazole obtained by recrystallization at 0 degrees C, 30 degrees C and 70 degrees C. Low magnification electron microscopy study of the crystals showed featureless morphology yet the resolved lattice images showed imperfections such as dislocations, lattice irregularities and regions of discontinuity.

The use of strain gauges for radial stress measurement during tableting.

The influence of size, configuration and positioning of die wall strain gauges on the measurement of radially transmitted stress developed during tableting was investigated. Calibration of strain gauges attached to a cutaway die wall was achieved by compression of rubber-like materials in the die, Breon Polyblend 504 being more effective than red rubber for this purpose. Hysteresis of response observed when calibrating a thin-walled die was possible due to excessive distortion of the weakened die wall although the extent of this hysteresis varied with calibration material. The use of full bridge arrangements produced an increase in response when the compression site was moved away from the gauges. The opposite effect was seen when half bridge arrangements, using two active gauges, were used. The paradoxical effect observed when full bridge arrangements were used was shown to be due to straining of the compensating gauges. The dependence of die wall response on compact position was substantially reduced by the use of multiple gauges mounted along the die length and connected together to form a single gauge on each side of the die.

The effects of polymorphism, particle size and compression pressure on the dissolution rate of phenylbutazone tablets.

The dissolution rate of phenylbutazone from tablets after disintegration has been used to determine whether the drug particles underwent crushing or bonding during compression. Two polymorphic forms of the drug were used and the predominant effect for high drug concentration (60%), during compression was dependent upon the original particle size of the drug and its polymorphic form. With a low drug concentration (10%) in the tablet, the diluent protected the drug particles from bonding together. The particle size change of the drug during compression was affected by the nature of the diluent present. Lactose had an abrasive action on Form A phenylbutazone compared with Avicel but had little effect on the more ductile Form B. When the contact time of compression was decreased from 29 to 0.26 s, the 6 microns particles of drug showed less bonding at the shorter time (faster rate of compression) but the effect observed with the larger particles was independent the compression rate.

Thermal behaviour and dissolution properties of phenylbutazone polymorphs.

Five different polymorphic forms of phenylbutazone were prepared and characterized by differential scanning calorimetry (D.S.C.). Rapid heating rates produced single endothermic peaks due to melting but slower heating rates resulted in interconversion of three of the polymorphs to the more stable form. Interconversion on grinding the polymorphs was also observed. From equilibrium solubility and intrinsic dissolution rates it was concluded that the dissolution process could be described by the Berthoud model. The effect of some tablet excipients on the dissolution process is briefly reported.

Glass formation in barbiturates and solid dispersion systems of barbiturates with citric acid.

Glasses were prepared from a number of barbiturates. The viscosities and glass transition temperatures of the glasses were dependent on the structure of the groups present on the C-5 and N-1 atoms. Solid dispersions were prepared from three selected barbiturates formulated with citric acid. The glass transition temperatures of these systems indicated that a 1:1 molar ratio complex was formed between the two components and that intermolecular bonding was stronger in the complex than in the individual components.

Influence of crystal form on tensile strength of compacts of pharmaceutical materials.

The tensile strengths of compacts of different crystal forms of aspirin, sulfathiazole, and barbital were determined with a modified tablet hardness tester. For each material, the tensile strength could be correlated with the amount of plastic flow and/or crushing undergone by each crystal form during compression.

Effect of primidone concentration on glass transition temperature and dissolution of solid dispersion systems containing primidone and citric acid.

The glass transition temperatures of glasses containing various concentrations of primidone in citric acid were measured and found to increase as the primidone concentration increased. Dissolution studies of these systems and particle-size measurements of primidone precipitated during dissolution of devitrified glasses suggest that the increase in the dissolution rate of the devitrified systems is due to both the small size of the precipitated crystals and the excellent wettability of these systems.

Preparation and properties of solid dispersion system containing citric acid and primidone.

Solid dispersions containing 1--32% (w/w) primidone were prepared by fusing the drug with citric acid and rapidly cooling the melt. The solidified dispersions were clear glasses which devitrified on aging or when stored at 60 degrees for up to 3 days. The phase diagram of the devitrified system indicated that the drug may exist as a solid solution at 1--3% (w/w) concentrations but that a eutectic mixture is formed at higher concentrations. The solubility of primidone increased in the presence of citric acid. Preliminary dissolution studies showed that the dissolution rate from the solid dispersion was greater than that of the pure drug or the physical mixture.

The influence of crystal form on the radial stress transmission characteristics of pharmaceutical materials.

Various crystal forms of sulphathiazole, barbitone and aspirin were compressed in a single-punch tablet machine instrumented to monitor axially applied and radially transmitted forces, and upper punch movement. The changes in radial stress during the compression cycle depended upon the polymorphic form of the compressed material. The results were rationalized in terms of the degree of plastic flow/crushing that occurred with each material, and the degree to which the final compact underwent elastic compression. It is postulated that the reduction in the transition temperature of polymorphic forms of sulphathiazole and barbitone and the polymorphic transition of sulphathiazole Form II was due to the production of dislocations in the crystal and the crystals at crystal boundaries formed in the compressed materials.