Evaluation and comparison of magnesium stearate and sodium stearyl fumarate (Pruv) as lubricants in directly compressible tablet formulations : their effect on tablet properties and drug dissolution

Abstract

The most widely used lubricant in the pharmaceutical industry is probably magnesium stearate. Magnesium stearate exhibits its lubricating properties by forming a film of low shear strength between the die wall and the compact, thus reducing the friction (Banker & Anderson, 1986:306). It also exhibits anti-adhesive and flow enhancement properties by preventing tablets from sticking to the die wall and punch faces and ensuring uniformity of tablets. Besides these advantageous properties, the lubricant forms a hydrophobic film around the carrier particles which can negatively affect the tablet properties such as crushing strength, disintegration time, friability and dissolution (Bolhuis et al., 1975:324; Levy & Gumtow, 1963:1142). Due to the deleterious effects on the tablet properties, lubricant concentrations must be restricted to an absolute minimum. These effects are known to increase with prolonged mixing, and in practice one tries to keep the lubricant mixing time as short as possible (Ragnarsson et al., 1979:130). It has been shown that the die wall film of magnesium stearate is resistant to wearing off and the lubricating effect remains for several compactions when an unlubricated granulation is added to a lubricated die (Holzer & Sjogren, 1981b:276). The lubricant film around the particles is formed during the final mixing, while the film at the die wall is formed during the compaction. This implicates that the lubricant is mixed for shorter (mixing) times with the other excipients in the formulation. Sodium stearyl fumarate (Pruv®) has been suggested as a suitable lubricant in tableting (Mendell, 2002:5) and it is claimed not to have the disadvantages of magnesium stearate in respect of tablet strength, disintegration and dissolution (Lindberg, 1972:213). These properties could prove advantageous regarding tablet strength as well as drug release properties (especially for immediate release tablet formulations). Since the primary function of lubricants is the reduction of friction, it was this property that provided the challenge that was circumvented in this study. The addition of the sparingly water-soluble, hydrophobic drug, furosemide, perplexed the formulation of tablets, however, provided a mode of evaluation of the effects of formulation variables on tracer substance dissolution behaviour. Systematic evaluations of various commercially available excipients were investigated to determine their effects on the physical tablet properties as well as on tracer dissolution. Magnesium stearate or Pruv® was incorporated into Avicel® PH-200, Emcompress® and Tablettose® fillers/binders. Mixing time was varied between 1 and 16 minutes and mixing speed between 33 and 97 rpm under certain specified testing environments in a Turbula® mixer. Compression was done with a Manesty® F3 single station tablet press with biconcave punches (10 mm). Evaluation on the powder and the compressed formulation was done. The aim was to evaluate and compare the lubricant, glidant and antiadherent properties of magnesium stearate and Pruv®, as well as the effect both had on tablet properties (crushing strength, friability and disintegration) and drug release. It was found that magnesium stearate had superior glidant properties compared to its counterpart as a result of its flatter particle shape and larger specific surface area. Lubricant concentrations below 0.5% w/w gave optimum glidancy for both lubricants and mixing times between 4 and 8 minutes was sufficient to optimize this glidant effect. Tablet strength decreased when lubricant concentration increased, due to less interparticulate binding surface between the carrier particles. This decrease subsided when lubrication surpassed the 1.5% w/w concentration level. Mixing, however, had the opposite effect on Pruv® than on magnesium stearate, since Pruv® increased the tablet strength with continuous mixing. Disintegration and dissolution deteriorated with the addition of magnesium stearate and Pruv®. This was due to the hydrophobic nature of magnesium stearate and increase in tablet strength observed with Pruv®. The evaluation of the extent of drug release (AUC) and rate of release (DR|) indicated of an average increase of 50% in drug release in formulations with Pruv® compared to magnesium stearate as lubricant. Magnesium stearate had superior lubricant and antiadherent properties as opposed to Pruv® and optimum lubricant efficiency was experienced at low concentrations (< 1% w/w) and low mixing times (< 4 minutes). The apparatus and methods for lubricant evaluation were newly developed and gave accurate, repeatable measurements.