The application of non-contact laser profilometry to the determination of permanent structural changes induced by compaction of pellets: I. Pellets of different composition

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Abstract

Pellets of different mechanical properties were produced by extrusion and spheronisation process based on various composition (microcrystalline cellulose (MCC), lactose, glyceryl monostearate (GMS), water, ethanol and glycerol). Six hundred milligrams of these pellets were compacted at two different pressures (86.7 and 130 MPa) to form flat-faced tablets and stored for 48 h in ambient temperature and humidity after which their permanent structural change (plastic deformation) was investigated in terms of surface roughness parameters of both faces of the tablets, using a non-contact laser profilometer. The results were compared with the deformability values obtained from the force/displacement curve as well as the phase angle values obtained from the dynamic scan of a dynamic mechanical analyser. The increase in deformability of the pellets with the increase in porosity, increase in the contents of GMS, lactose or ethanol in the formulations and increase in compaction pressure was illustrated by the reduction of the surface roughness parameters. Analysis of variance identified the significant difference in the mean rugosity values of the tablets from the various formulations, tablet faces and compaction pressures. The deformability values obtained were reasonably comparable to those plasticity values obtained in terms of phase angle from the dynamic scan of the DMA and the force/displacement curves. The laser profilometry technique in conjunction with scanning electro-microscopy (SEM) demonstrated the low and broad based wavelike structure of the pellets after compaction rather than spiky sharp protrusions. This confirms the capability of determining the plastic deformability of the pellets from the surface roughness parameters obtained from non-contact laser profilometry.

Introduction

In pharmaceutical technology there is an ever increasing desire to improve and optimise the function and quality of pharmaceutical tablets. One factor related to tablet quality that has great importance is surface roughness. Surface roughness was observed to be closely related to the tablet porosity (Ozkan and Briscoe, 1996), dissolution rate (Healy et al., 1995), fracture by crack initiation and propagation (Podczeck, 1998a), compaction pressure (Toyoshima et al., 1988, Riippi et al., 1998, Podczeck et al., 1999a), powder properties (Podczeck et al., 1999a), mixing time and lubricant added during tableting (Toyoshima et al., 1988).

According to the British Standard (BS 1134, 1972), the surface roughness of materials can be evaluated by profilometry, which classically uses a transducer fitted with sapphire or diamond-tipped stylus mounted on a pick-up arm. The transducer is driven across the surface at a steady rate. The vertical movement of the stylus as it follows the surface irregularities produces an electrical signal proportional to the local height of the surface. This is then processed in various ways after amplification to give a three-dimensional surface roughness value. Nadkari et al. (1975) and Rowe, 1977, Rowe, 1978a, Rowe, 1979 employed the technique to interpret the relationship between tablet surface roughness and film adhesion. Additionally, the effect of some formulation and processing variables (Rowe, 1978b) and the particle size of an inert additive (Rowe, 1981) on the surface roughness of tablets were investigated using the stylus instrument. However, the inability to measure directly the three-dimensional surface profile, the limited resolution due to relatively larger size of the stylus (2.5–5 μm), and the possible destruction of the surface as the stylus runs along the surface (Healy et al., 1995), the longer duration and labour it needs (Riippi et al., 1998) as well as its irreproducible results (Silvennoinen et al., 1999), has restricted the application of such instrument to study pharmaceutical compacts. As an alternative to the stylus instrument, Healy et al. (1995) used non-contact laser profilometry to examine the surface texture of model solid-dosage forms prior to and following dissolution up to various times. Podczeck (1998a) employed the same technique to measure the change in surface roughness of the tablets made from polyethylene glycol powders of various molecular weights after friability test. In a further study, Podczeck et al. (1999a) established the potential of this technique in identifying the influence of powder properties and tableting conditions on the surface roughness of tablets in comparison to a single line profile measurement.

A non-contact laser profilometer uses an infrared light from a semiconductor laser focussed on the surface by an objective lens. The light reflected by the object surface is directed to a beam splitter through a prism, and is imaged as a pair of spots (1 μm in diameter) onto an arrangement of photodiodes. When the objective lens is exactly at its focal distance from the surface, both diodes are illuminated equally. If the distance between the object surface and the objective lens is altered, the imaged focus point is shifted and the illumination of the photodiodes become unequal. This generates a focus error signal by means of a differential amplifier. A control circuit monitors the focus error signal and controls the position of a moveable lens suspended within the sensor, so that the focal spot of the beam remains coincident with the measurement surface. The changing illumination of the photodiode is translated into amplitude parameters, which measure the surface roughness, such as Ra, Rq, Rt, Rtm and FD.

The Ra (rugosity) value is the most widely used parameter of surface roughness. In the case of a line scan of the surface, it is the arithmetic mean of the departure of the profile from the centre line and is expressed by Eq. (1). In an area scan it is the arithmetic average of the absolute values of all points of the profile and takes the form of Eq. (2).Ra=1ni=1nZiwhere, n is the number of measurement points and Zi is the ith point.Ra=1nmi,j=1n,mZijwhere n is the number of measurement points, Zij is the ith point in the jth row where the number of rows is m.

The Rq (μm) value is the “root mean square deviation” of all points of the profile from the centre line and characterises the variability of the profile from the centre line.Rq=1ni=1nyi2

The maximum peak to valley height, Rt, represents the difference between the maximum and minimum points of the profile (Fig. 1). In the case of a line scan of the surface, the Rtm value is the arithmetic average of the five sampling sections of Rt values obtained during the assessment and is expressed by Eq. (4).Rtm=15i=11RtiIn case of an area scan, the Rtm value is the arithmetic average of the maximum peak-to-valley height Rti in each of 25 rectangles, which result from splitting the surface into a 5×5 grid. The fractal dimension (FD) is a scale-dependent method of characterising surface topography (Wieland et al., 2000). A large number of analytical strategies have been developed to allow the measurement of fractal dimensions (e.g. Allen et al., 1995). In a three-dimensional roughness profile, the fractal dimension takes up values between 2 (perfectly smooth surface) and increases with the surface roughness up to 3 (Podczeck, 1998b). In practice, however, the fractal dimension was found to be less sensitive to changes in the surface roughness identified by the other parameters (Riippi et al., 1998, Podczeck, 1998a, Podczeck et al., 1999b).

If the pellets were compacted, the variation in the smoothness of the pellet surface could be underestimated by the macroscopic curvature of the pellets due to incomplete deformation to form flat-faced tablets. The impact of such convex structure on surface roughness parameter measured by non-contact laser profilometer was discussed by Silvennoinen et al. (1999). Salako et al. (1998) introduced the surface roughness parameters as a means to assess the deformability of soft and hard pellets after compaction. Rowe (1979) suggested that the nature of the overall surface profile could be indicated by the ratio of some of the parameters. For instance as the ratio between the distance between the highest peak and centre line, Rp, to the distance between the highest peak and the deepest valley, Rt, decreases the peaks becomes more rounded and broad based. Thus, determination of the plastic (permanent) deformability of the pellets from the surface roughness parameters becomes possible as suggested by Salako et al. (1998).

The objective of this work is to examine the applicability of this technique in determining the permanent structural change (plastic deformability) of pellets of a range of mechanical properties produced from different formulations and processing factors after compaction. It is also designed as part of a wider study to compare the values obtained from non-contact laser profilometer with those obtained from dynamic mechanical analysis and diametral compression test by Bashaiwoldu et al. (2003), when considering the influence of the mechanical properties of core pellets on the fracture of the coating of pellets, which have been coated to provide controlled release formulation and then compacted to from tablets.

Section snippets

Materials

The microcrystalline cellulose (MCC) used was Avicel PH-101, batch number CA01148 (FMC International, Little Island, Cork, Ireland) and had a mean volume particle diameter of 54.80±0.54 μm as measured by Malvern master sizer (Malvern, UK). It was used as received and incorporated in all the formulations studied as pelletisation enhancer. The lactose used was SorbaLac 400 having a mean volume particle diameter of 16.80±0.32 μm, batch number 022-000405 (Meggle GmbH, Wasserburg, Germany). The

The effects of composition

The starting formulation in this work was a mixture of MCC:water (1:1). The pellets from this starting formula could not form tablets presumably due to the confinement of the MCC fibres, the strong and elastic nature of the pellets, as well as the change in the surface nature of the pellets which reduced the connectivity between each other during compaction. This reduction in consolidation or strength of the compacts of the MCC pellets was probably associated with the same mechanisms which

Conclusion

The increase in deformability of the pellets with the increase in the contents of GMS, lactose or ethanol from 40 to 60% (w/w) in the preparation of the pellets was illustrated by the reduction of the surface roughness parameters of tablets prepared from the pellets. Moreover, the increase in compaction pressure enhanced the deformability of these pellets. The rank order of the formulation factors effect differed in that deformability values determined from the pressure/displacement curve

Acknowledgements

Dr. Abraham Bahre Bashaiwoldu would like to thank the University of Asmara, the Italian Cooperation and the World Health Organization for funding this project (WHO reference: Project—PHARPE; Reg. File—H15/370/2).

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