New direct method to measure true density of powders during tablet compression and a modified method to draw Heckel plot. Osmo Antikainen 2015

Transcription

1 New direct method to measure true density of powders during tablet compression and a modified method to draw Heckel plot Osmo Antikainen 205

2 resentation Outline A new method to determine the true density of materials under compression pressure A method to carry out Heckel analysis in cases where it has been earlier impossible.

3 The Heckel equation has become the most widely used porosity-pressure function in the field of pharmaceutical compression research. ln True ln D k A For a powder in cylider, the density can be calculated by deviding its mass with volume m tablet V m Ah tablet where : (Ma m tablet A h = mass of the tablet, = area of the punch head, = distance between the upper and lower punch

4 For some pharmaceutical materials it is not possible to draw Heckel plot to a wide pressure range. This is because the measured density values of the material seem to exceed its true density (measured at zero compression pressure at certain compression pressure level Aspirin(Acetylsalicylic acid; ASA, and ibuprofen (IBU are examples of materials where measured density values at high compression pressures exceed true densities determined by helium pycnometer ln True k A Heckel plot of Acetylsalicylic acid

5 Explanation to this phenomenon may be: artial melting of the powder owder may have closed pores or bubbles that are not accessible to the probe gas. olymorphic transitions of the molecular crystals Reduction of the crystal volume itself under high pressure. S. edersen H.G Kristensen: Change in crystal density of acetylsalicylic acid during compaction. S.T. harma Sciences 4 ( Unit cell of ASA

6 ASA Densification of powder bed during tablet compression is assumed to consist of three main stages:. rearrangement of particles 2. plastic deformation of particles. particle fracture. These three stages overlap each other during compression process. Depending from the nature of the powder one of the stages is dominating at different compression levels. These kinds of densifications proceed typically exponentially. 2 ( ( e ( e ( e 0 2 true, max 0 2

7 /.47 / ( ,max cm g cm g true ( ( ( ( e e e ASA

8 IBU.2 2 ( ( e ( e ( e True,max true,max 0 2 ( g / cm.5g / cm Average density of the powder (g/cm Measured data points Function fit (Eq Compression pressure (Ma

9 ( ( ( ( e e e A k True ln

10 When we start to compress powder bed in the die, the pressure is transmitted trough small contact points between particles. At the beginning of the compression process the true density of the powder is the same value as measured with helium densitometer. The pressure is in narrow contact points in the powder bed remarkably higher than the average pressure that is transmitted to the punch. At these points the true density of the powder starts to increase first When the compression pressure increases the contact area between particles increases because the porosity of the tablet decreases

11 Determination of true density at different compression levels.48 ASA True (g/cm True = 0.04* = g/cm =.47 g/cm (g/cm 50 Ma, =.4 g/cm True = g/cm +.2 g/cm =.46 g/cm

12 The true density of ASA and IBU as a function of compression pressure

13 A k true ln A k true ( ln Heckel plot using both traditional and new method to calculate the curve.

14 X-ray diffraction patterns of Acetylsalicylic acid n 2d sin

15 Diamond anvil cell A diamond anvil cell (DAC is a device used in scientific experiments. It allows compressing a small piece of material to high pressures. The pressure-transmitting medium is enclosed by a gasket and the two diamond anvils. The sample can be viewed through the diamonds and illuminated by X-rays. In this way, X-ray diffraction can be measured from materials under high pressure.

16 CONCLUSIONS The true density of some pharmaceutical powders is not a constant but a function of compression pressure The true density of powders is possible to determine by compression method in a tablet machine. Compression method gives higher true density values than helium densitometer for some pharmaceutical powders The presented new modified Heckel plot makes it possible to carry out Heckel analysis in high compression levels in cases where it has been earlier impossible.