Wettability studies of morphine sulfate powders

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Abstract

A capillary penetration technique was used to determine the wettability of morphine sulfate powders by a range of wetting and partially wetting liquids. Wetting rates were found to be dependent on both the properties of the wetting liquid and the morphine sulfate batch. A number of liquids were established as perfectly wetting, and the critical surface tension for morphine sulfate wetting was estimated to be ∼40 mN m−1. Effective capillary radii for packed beds of morphine sulfate powders were determined in the range 0.3–0.6 μm; these are compared with particle size, shape and surface area data. From the Washburn approach, the advancing water-particle contact angles for the different morphine sulfate samples were determined to be in the range 57–79°, with errors less than ±3°. Sessile drop measurements on the same samples were unable to determine reproducible equilibrium contact angles and could not differentiate between the batches. The role of surface chemistry, crystal morphology and crystal structure in controlling morphine sulfate powder wettability was explored by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and X-ray diffraction. Contact angles were shown to correlate with both the aspect ratio of the morphine sulfate crystals and the nitrogen-to-oxygen surface atomic concentration ratio, determined by SEM and XPS, respectively. The relative exposure of different crystal faces is considered to play an important role in controlling the wettability of morphine sulfate powders.

Introduction

The physical characterisation of drug particles, both in terms of their bulk and, more importantly, their surface properties, is critically important in the search for novel or improved drug delivery systems. Drug particle wettability is one such surface property that has not been fully utilised in this regard. Since wetting is the precursor to dissolution, drug particle wettability has a controlling influence on dissolution rates and may therefore be engineered to control release characteristics in oral pharmaceutical delivery. Drug particle wettability is also influential in controlling interactions with other drug particles, and particle and polymer excipients during formulation and manufacture. Wettability therefore plays an important role in both dry powder and suspension processing, e.g. in controlling the interfacial stability (Parsons et al., 1992), which is critical in controlling coating and granulation processes. It is also noteworthy that drug particle wettability can be significantly influenced during crystallisation, milling and compaction, although the consequences of this on subsequent processing are rarely considered. With these thoughts in mind, drug particle wettability may be directly used in controlling the quality of raw materials in formulation and in process optimisation during manufacture (Wells and Walker, 1983, Zajic and Buckton, 1990). For these to be achieved, reliable and convenient methods for the measurement of drug particle wettability are required and these should generate parameters that are representative of the drug particle behaviour during processing and/or delivery.

The contact angle is generally used to characterise the wettability of material surfaces and is commonly determined by sessile techniques, where the angle of contact of a water drop or a bubble on a surface is measured through the liquid phase. Sessile methods can be reliably used for determining the contact angle of large single crystals. They have also been widely applied to compressed discs of pharmaceutical powders (for example, Harder et al., 1970, Buckton and Newton, 1986a). It is, however, questionable whether such wettability measurements are representative of the parent drug particles. Compaction may influence both the surface energy and the surface roughness of a powder, and has been shown to decrease the contact angle of barbiturate powders (Buckton and Newton, 1986a). Sedimentation volume (Duncan-Hewitt and Nisman, 1993), vacuum microbalance (Buckton et al., 1986) and microcalorimetric (Buckton and Beezer, 1988) techniques have also been applied to characterise the wettability of pharmaceutical powders. They do not, however, directly determine the contact angle, and comparison between different techniques may not be simple.

Methods for direct contact angle measurements on powders are based on liquid penetration into particle beds. Equilibrium capillary pressure (Diggins et al., 1990) and wetting rate techniques (Washburn, 1921) have been developed for application with inorganic mineral particles (Yang et al., 1988, Diggins et al., 1990, Prestidge and Ralston, 1995, Subrahmanyam et al., 1996), but have been less frequently applied to organic drug particles (Alkan and Groves, 1982, Buckton and Newton, 1985, Buckton and Newton, 1986b, Kiesvaara et al., 1993). Problems in terms of partial wetting and irreproducible wetting rates have been encountered (Buckton, 1993); however, given the simplicity and direct nature of these techniques, further studies are warranted.

The major objective of the present work was to use wetting rate measurements of particle-filled capillaries to determine the contact angles of morphine sulfate particles from different sources. Comparisons are made with sessile drop contact angles on compressed discs of the same morphine sulfate powders. Complementary characterisation studies using X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were undertaken in an attempt to rationalise the observed differences in particle wettability. These studies were employed to further develop the relationship between drug particle surface chemistry, wettability and processing performance.

Section snippets

Materials

Water was purified by reverse osmosis and subsequently passed through a Millipore Super-Q system; it had a conductivity of <0.5 μS m−1. Surface tensions of the water and water saturated with morphine sulfate were determined using a Wilhelmy balance, and were found to be 72.8 and 71.5 mN m−1, respectively. Other reference wetting liquids were spectroscopic grade reagents; their surface tension and viscosity data are given in Table 1. Seven different powder samples of morphine sulfate

Sessile drop measurements of contact angle

Sessile drops of water saturated with morphine sulfate placed on the surface of a compacted surface of morphine sulfate particles exhibited time-dependent behaviour, as exemplified for samples A, D and E in Fig. 1. For all samples, the advancing water-particle contact angles decreased from ∼50 to ∼20° in less than 1 min. The apparent equilibrium contact angles were less than 20°, but these were not, however, reproducible and not considered representative of the drug particle properties. Factors

Conclusions

Sessile drop measurements are inappropriate for determining the advancing water contact angle of morphine sulfate powders. A capillary penetration technique has determined significant differences in the wettability of morphine sulfate samples from different sources. A range of perfectly wetting liquids have been identified and the critical surface tension for wetting estimated to be ∼ 40 mN m−1. The Washburn method enabled particle contact angles to be determined with good reproducibility.

Acknowledgements

Financial support from the Australian Research Council’s SPIRT grant scheme and F.H. Faulding & Co Ltd is gratefully acknowledged. David Hayes, John Gates and Rob Hayes are thanked for helpful discussion. The Surface and Materials Processing Group at the Ian Wark Research Institute, University of South Australia are thanked for surface analysis, and Tim Muster is acknowledged for assistance with the sessile drop measurements.

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