Carr's Compressibility Research Articles

Modification of Crystal Habit of Ibuprofen Using the Phase Partition Technique: Effect of Aerosil and Tween 80 in Binding Solvent

A ternary diagram, representing the solubility of binding solvent (chloroform) in a mixture of ethanol and water, was constructed. For this study, the solvent mixture that gave the best ibuprofen pellets (IPs) was composed of chloroform:ethanol:water at a ratio of 1.5%:8%:90.5%. The suitable agitator speed, temperature, and mixing time were found to be 1500 rpm, 25°C ± 2°C, and 20 min, respectively. In addition, suitable stirring time when the phase partition process of IPs began was 15 min. IPs obtained from these conditions were small and round, approximately 1 mm; surface determination by scanning electron microscopy (SEM) indicated that the IPs were composed of drug microcrystals rearranged on the surface. For the dissolution, IPs showed lower drug release when compared with pure ibuprofen crystal (IC) (f2 analysis). An attempt to modify the dissolution property of IP by incorporating various concentrations of Aerosil and Tween 80 in the binding solvent was made. Microscopic appearance showed that both Aerosil and Tween 80 gave less spherical pellets when compared with the use of binding solvent alone. For both the Aerosil and Tween 80 employed, the results indicated a change in rearrangement of drug microcrystals and a change in crystal habit. However, Tween 80 gave more change of the crystallographic direction of drug microcrystals than Aerosil. In term of dissolution, the results showed that employing Tween 80 at 1.2% gave the highest drug release compared to the use of Aerosil and IC alone (f2 analysis). These pellets had a good flow property, as indicated by Carr's compressibility, flow rate, and angle of repose, and they can be compressed into a tablet, encapsulated by suitable polymer, or pulverized to obtain micronized crystals. In the case of compression into tablets, the dissolution profiles of these tablets compared with those of commercial product meet the USP 24 requirement (Q ≥ 80% at 60 min).

Powder and capsule filling properties of lubricated granulated cellulose powder

Granulated powdered cellulose was studied in terms of powder bulk properties and capsule filling performance on a tamp-filling machine with and without the addition of various concentrations of magnesium stearate. Carr's compressibility reached its minimum value at 0.4% magnesium stearate suggesting an improvement of powder flow compared to the unlubricated material. However, shear cell measurements and the use of a powder rheometer indicated that the addition of 0.2% magnesium stearate and more impairs powder flow and does not reduce interparticulate friction. When capsules were filled into hard gelatine capsules at a zero-compression setting, the fill weight and plug density could be predicted from Carr's compressibility index and from the maximum bulk density. The decrease in one and simultaneous increase in the other bulk property with increasing magnesium stearate concentration caused both fill weight and plug density to go through a minimum at a lubricant concentration of 0.4%. When the capsules were filled at maximum compression, however, the addition of lubricant increased the coefficient of fill weight variation significantly, and the plug density remained constant for any added concentration of magnesium stearate. These findings were in agreement with the shear cell and powder rheometer results. However, the optimum lubricant concentration in terms of ease of machine function, which was identified from tamping pressure measurements, was found to be 0.8% magnesium stearate, which was not an optimal concentration for the powder bulk properties.

Development of a dual approach to assess powder flow from avalanching behavior

The purposes of this investigation were to develop a method to evaluate flow properties of powders from avalanching tests and to detect similarities and relationships between these data and conventional powder flow properties. The API AeroFlow automated flowability analyzer was tested using 6 pharmaceutical excipients. Data were presented as mean time to avalanche (MTA), scatter, and a classification based on the type of motion of the powder bed. Powders were also characterized in terms of particle size, particle shape, loss of weight on drying, Carr's compressibility index, and critical orifice diameter to prevent ratholing. A dual approach, which combines visual observation of the type of motion of the powder bed in the rotating drum with numerical descriptors such as MTA and scatter, was found to be more accurate in the assessment of powder flow than the current practice of using only MTA and scatter values. Statistical analysis established that there are relationships and similarities between the ranking of powder flow properties obtained from the avalanching test and Carr's compressibility index and the critical orifice diameter. An interaction between particle size and shape, both influencing powder flow, when evaluated with these methods was found. The assessment of the flowability of powders on the basis of avalanching tests should include both the determination of numerical descriptors of flow such as MTA and scatter, and a determination of the type of motion of the powder bed in order to increase the sensitivity of the method to small changes in powder flow properties.

The bulk volume changes of powders by granulation and compression with respect to capsule filling

Experiments were performed to study the possibility of predicting the bulk volume changes of a powder bed due to granulation and/or low compression, to aid the development of powder filled hard gelatin capsules. Granulation techniques used were a high speed mixer/granulator and an oscillating granulator. For each of a series of typical filler powders and the granules produced from them, the tapped volume and the Kawakita constant a were determined on the basis of tap density volumetry. The Kawakita constant was also obtained from low compression experiments using a Höfliger and Karg powder plug simulator. Only the granules produced in the high speed mixer/granulator partly provided a reduced tap volume, whereas the processing by an oscillating granulator resulted generally in an increased tap volume. For the decrease in volume, a limiting value of the tap volume of the original powders of 1.4 cm 3/g appears to exist. Powders with a tap volume below this threshold cannot be densified by granulation, whereas the degree of possible volume reduction increases with an increase in tap volume above the limiting value. After application of a sufficient number of taps, Carr's compressibility index and the Kawakita constant a are similar in value. However, the Kawakita constant a is increased by on average 5% if determined using low compression. Thus, the application of the Kawakita equation has no advantage over the use of Carr's compressibility index as an indicator of possible volume reduction. Therefore, an estimate of the volume reduction due to low compression can be found by adding 5% to Carr's compressibility index. A combination of granulation and compression to further densify a powder failed in providing smaller plug volumes. Hence, if a reduction in capsule size is the only reason to use a densification method, low compression is preferable to granulation.

Powder flowability as an indication of capsule filling performance

The flowability of size fractions of 5 pharmaceutical excipients has been related to their capsule filling performance. Using angular, packing and shear tests, the samples were ranked in different relative orders of flowability. The powders were filled on an instrumented mG2 capsule filling simulator fitted with a size 1 dosator. Capsule fill weight and weight uniformity were monitored and the coefficient of variation ( X cv) of the fill weight of 20 capsules was used as an indicator of capsule filling performance. Flowability was dependent on the particle size, morphology and bulk density of the powder. There was a significant correlation between the values of X cv and the flow parameters of Carr's compressibility, Hausner's ratio, angle of repose, Kawakita's equation constant ( a) and Jenike's flow factor. X cv was also related to the coefficient of variation of the powder bed bulk density and the variation in the compression stress. There was, however, no correlation between the values of X cv and the angle of internal flow and the angle of effective friction.