J. E. Rees

Time-dependent deformation of some direct compression excipients*

Three techniques were used to compare the time‐dependent deformation of microfine cellulose (Elcema G250), anhydrous lactose, dicalcium phosphate dihydrate (Emcompress), modified starch (Sta‐Rx 1500) and sodium chloride. (1) In stress‐relaxation experiments using a reciprocating tablet machine, none of the materials behaved as a Maxwell body in contrast to recent published work (David & Augsburger, 1977). Possible reasons for this disagreement are discussed. (2) Heckel plots showed that increasing the time for which a material was under compression (contact times of 0·17 and 10 s) had no effect on dicalcium phosphate compacts but increased the consolidation of other materials in the rank order sodium chloride < lactose < cellulose < starch. (3) Deformation tests on preformed compacts were carried out in diametral compression by loading compacts to 75% of their breaking force at four different strain rates between 0·05 and 6·5 mm min−1. The deformation of Sta‐Rx compacts was time‐dependent. Sodium chloride compacts exhibited brittle behaviour in the diametral compression test and in the 10 s contact time experiment. This was apparently due to work‐hardening, following the extensive plastic deformation of crystals during compaction as indicated by the stress relaxation results.

Electrostatic charge interactions in ordered powder mixes.

A method is described for measuring the electrostatic charge generated in powders following contact with a plane substrate. The method uses a Faraday well connected to an electrometer and allows the specific charge of powders to be determined. Of the various drugs and excipients studied, most charged electronegatively following contact with glass surfaces, but became electropositive after contact with polyethylene surfaces. The charge interactions of drug and excipient powders modified the behaviour of ordered mixes formed in similar conditions to those of charge measurement. Powders with like charges formed less stable ordered mixes than those in which drug and excipient particles carried opposite charges. Following triboelectrification in an air cyclone constructed of brass, powders had charges at least 100 times greater than those formed after contact with glass surfaces. Optimization of the triboelectric charging conditions allowed ordered mixes to be prepared in which a maximum electronegative charge was applied to the excipient whilst the drug was given a maximum electropositive charge. Studies of segregation/stability showed that ordered mixes subjected to triboelectrification were less prone to segregation than uncharged powders.

Limitations of the Heckel relation for predicting powder compaction mechanisms

Recently York (1977) used the Heckel (1961) equation to interpret the consolidation of powders during compaction at low pressures. He states that this equation may be used to elucidate compression behaviour at higher pressures and that such behaviour may be divided into three types, termed A and B (Type 1 and 2 of Hersey & Rees, 1971) and C (York & Pilpel, 1973) depending on the effect of particle size on the Heckel plots. We now believe that caution is necessary in attempts to classify the compaction behaviour of materials on the basis of changes in the Heckel plots with particle size. As explained below, there is considerable evidence that the type of Heckel plots obtained for many materials will vary depending on the experimental compaction technique used. Furthermore, since different particle size fractions of the same material may exhibit changes in the predominant compaction mechanism ranging from brittle to plastic deformation (Gregory, 1962), we are reluctant to classify a material using data for a range of particle sizes. Hersey & Rees (1970) using the compaction data of Hersey, Bayraktar & Shotton (1967) found that, in a 12 mm diameter die, the Heckel plots for various size fractions of sodium chloride were non-linear up to an applied compaction pressure of 50 M N m-2 and showed a separation of the plots at all pressure levels. York (1977) suggests that this is Type A behaviour, characteristic of a material which consolidates mainly by plastic deformation. In later experiments using a 33 mm die and various size fractions of sodium chloride, Hersey, Cole & Rees (1972) obtained completely linear Heckel plots up to an applied compaction pressure of 60 MN m-2 and no separation of the plots was found. Using the data of Alpar, Hersey & Shotton (1970), Hersey & Rees (1970) investigated the effect of lactose particle size on the Heckel plots. The amount of powder compacted was sufficient to produce a 4 mm thick compact at zero porosity in a 12 mm die and the volume of the compact was determined after ejection. Under these conditions, above an applied pressure of 50 M N m-2 the Heckel plots were linear and identical for

Effect of vibration time, frequency and acceleration on drug content uniformity

The effect of different vibration conditions on the segregation tendency of three ordered powder mixes was studied. Segregation of the powders was measured using a cylinder, composed of interlocking units for sampling purposes, mounted on a vibration rig. Ordered mixes containing either Emdex or recrystallized lactose carrier particles mixed with 0.5% fine‐particle potassium chloride were stable, except for slight segregation that occurred under severe vibration conditions at frequencies below 50 Hz and accelerations above 22 m s−2. Powder mixes of Dipac with potassium chloride were unstable at most vibration conditions from 20 to 1000 Hz and 7.4 to 29.4 m s−2. The intensity of segregation in vibrated mixes of Dipac with potassium chloride was most marked at frequencies below 50 Hz and accelerations above 22 m s−2. These vibration conditions were found to occur in several commonly‐used types of tableting presses. When vibration was prolonged, for periods of 30 to 60 min, there was increased segregation found in ordered mixes.

Segregation of vibrated powder mixes containing different concentrations of fine potassium chloride and tablet excipients

The effect of different drug/excipient concentrations on the segregation tendency of three ordered powder mixes was studied. In addition, the influence of vibration frequency on the segregation intensity and mechanisms of segregation was also studied. Differences in content uniformity of the powders were measured by comparing samples from regions at different depths between the upper exposed powder surface and the base of the cylindrical container. Ordered mixes containing recrystallized lactose excipient and fine‐particle potassium chloride as a model drug were found to be least susceptible to segregation at most vibration conditions for all potassium chloride concentrations. Dipac excipient/potassium chloride particles were most susceptible to segregation under all test conditions. In general, segregation intensity was most marked in conditions where high potassium chloride concentrations, above 2% w/w, were subjected to low‐frequency vibration, below 100 Hz. Segregation mechanisms were considered to be mainly dependent on vibration conditions, although carrier excipient type markedly modified mechanisms and influenced segregation intensity.

QUANTIFYING AGITATION CONDITIONS IN COMPENDIAL DISSOLUTION TESTS

The r o t a t i n g b a s k e t d i s s o l u t i o n t e s t s of t h e BP and USP p r e s e n t d i f f i c u l t i e s i n p r e c i s e s t a n d a r d i s a t i o n of equipment geometry, a g i t a t i o n , v i b r a t i o n and samFling procedure. I n t e r l a b o r a t o r y v a r i a t i o n might be reduced cons iderably if Standard p e l l e t s with a reproducib le d i s s o l u t i o n p r o f i l e were a v a i l a b l e (Hanson, 1977) for checking t h e o p e r a t i n g condi t ions o f t h e d i s s o l u t i o n equipment.