M. S. Spring

The effects of binder film characteristics on granule and tablet properties

The physical properties of cast films of four polymers, which are used as binders in tableting, have been determined. Films were equilibrated at different relative humidities and tested both in tension, at three rates of strain, and by the use of indentation to determine creep compliance and hardness of the film under load. Granules and compacts have also been made using the four polymers as binders and the properties of these have been measured. One of the polymers, starch, formed a paste that was difficult to mix adequately. With the other three polymers a positive correlation was found between compact crushing strength and the creep compliance, the ultimate tensile strength and the elongation at fracture of the cast films. A negative correlation was found between the compact crushing strength and the Brinell Hardness of the films.

The granulation of ternary mixtures: the effect of the solubility of the excipients

The importance of excipient solubility in wet granulation has been shown using mixtures of lactose and boric acid containing third components of differing solubility characteristics. Sucrose dissolved in the binder solution and increased the amount of liquid available to form liquid bridges between other solid particles and therefore increased the number of solid bridges when the damp mass was dried. Thus, stronger, larger granules were formed. The results obtained with Sta‐Rx 1500 and magnesium carbonate powders were also dependent upon the extent of solubility of these powders in the granulating solution.

The granulation of ternary mixtures: the effect of the wettability of the powders

Granules have been prepared by a standard method from ternary mixtures of lactose, boric acid and either sulphanilamide, heavy kaolin or salicylic acid, using an aqueous solution of polyvinylpyrrolidone as binder. The granules were examined for size distribution and for the work required to crush larger granules from each batch. For the same binder volume the mean granule sizes and resistance to crushing of the granules increased as the wettability of the third component increased. The detailed results are discussed in relation to powder wetting and the packing properties of powder mixtures.

The granulation of binary mixtures: the effects of the composition of the granulating solution and the initial particle size of one component on granule properties

The effect of total solvent volume and the presence of dissolved material (other than binder) in the granulating solution, on the properties of granules prepared from lactose: boric acid mixtures has been studied. The total volume of binder solution available to powder mixtures during massing determines the ultimate average size of granules produced. Part‐dissolution of powders being granulated contributes significantly to the average granule size by increasing the total solution volume and reducing the amount of powder to be wetted. Although the amount of PVP (binder) dissolved in the granulating solution contributed very little to granule size at the concentration examined, the combined effect of total volume of solution and amount of PVP present in the granulating solution determines granule strength and porosity. The effect of the initial particle size of lactose in a binary mixture with boric acid differs from its effect reported for single component systems.

The granulation of ternary mixtures containing lactose and boric acid with different starches

Ternary mixtures of lactose, boric acid and starch have been granulated by massing and screening. The properties of the granules have been compared with those resulting from granulation of blends of lactose and boric acid without starch. Potato, maize and rice starches have been studied as the third component at concentrations similar to those employed in tablet formulations. The starches caused a reduction in both mean granule size and granule strength. The effect is dependent on the proportions of the excipients. Increasing the amount of binder solution used gave bigger, stronger granules but did not compensate for the effects produced by the starches.

The influence of binder film thickness on the mechanical properties of binder films in tension.

Abstract— The physicomechanical properties of films of different thicknesses, made from methylcellulose and gelatinized maize starch, have been studied in tension. There was a linear relation between film thickness and tensile strength, toughness, elastic resilence and elongation at fracture. Youngs modulus increased with decreasing film thickness particularly with films with a thickness of less than 15 μM.

Investigations of the biosynthesis of novobiocin

The biosynthesis of novobiocin was investigated using isotopically labelled compounds. The amino‐group of the coumarin unit was found to be derived from tyrosine, other typical 7‐oxycoumarin precursors were not incorporated into the coumarin unit of novobiocin, 4′‐hydroxyphenylpyruvate was a better precursor of the substituted benzoic acid unit than was 4′‐hydroxycinnamic acid. A biosynthetic route to this unit of novobiocin is suggested. Synthetic pathways for 2′,4′‐dihydroxyphenylalanine‐1‐14C and 4‐hydroxybenzaldehyde‐U‐14C are reported for the first time.

The granulation of binary mixtures: the effects of the properties of the component powders on granules

Sulphanilamide and citric acid individually and in various proportions with lactose, have been granulated by massing and screening. There was an optimum blend, that produced granules of maximum mean size and strength, for each binary system examined. The proportion of the components of this optimal blend was dependent on the physical properties of the second component in a mixture with lactose. Results from three systems, lactose: boric acid, lactose: sulphanilamide and lactose: citric acid indicate that although part dissolution of powder during granulation is a factor affecting granule properties, in some systems other physical properties of the second component may become dominant. It is suggested that the combined effect of cohesiveness and wettability of the powders may make the major contribution to granule strength with the sulphanilamide systems. The ultimate mean granule size produced is determined by the wettability or solubility of the powders, or both, in all cases examined. The great affinity of citric acid for aqueous binder solution was the dominant factor determining the properties of granules prepared from lactose: citric acid mixtures.

The Effects of Inclusions and Conditions of Storage on the Mechanical Properties of Maize Starch and Methylcellulose Films

Abstract— Films of methylcellulose and gelatinized maize starch were tested in tension, with and without 0.01–10% of additive in the film. The effects of these inclusions on the physical properties of the films have been found to be statistically significant in almost every case. The films, with and without inclusions, have also been conditioned at four different relative humidities and the behaviour of these films has also been considered. In general films were weakened by the presence of additives particularly at higher concentrations. The properties of methylcellulose films were changed most at specific concentrations of the inclusions, this effect was not found with maize starch films. Plasticization of maize starch films was not achieved.

Analysis of factors affecting the mean sizes of granules produced from ternary mixtures of powders.

Multiple linear regression analysis has been used to relate the mean sizes of granules prepared from ternary mixtures of powders to such physical properties as particle size, solubility and wettability and to processing variables such as the amount of binder and the proportions of the different components. The major influences on granule size were the amount of binder and the affinity of the third component for the binder liquids.