Lubricants In Pharmaceutical Solid Oral Dosage Form

Lubricants are agents added in small quantities to tablet and capsule formulations to improve certain processing characteristics. A lubricant is added to reduce friction between movingsurfaces. There are three roles identified with lubricants as follows: 1. True Lubricant Role: To decrease friction at the interface between a tablets surface and the die wall during ejection and reduce wear on punches and dies. 2. Anti-adherent Role: Prevent sticking to punch faces or in the case of encapsulation, lubricants prevent sticking to machine dosators, tamping pins, etc 3. Glidant Role: Enhance product flow by reducing interparticulate friction. A good lubricant requirements: 1. 2. 3. 4. 5. 6. Low Shear Strength Able to form a durable layer over the surface covered. Non-Toxic Chemically Inert Unaffected by Process Variables Posses Minimal Adverse Effects on the Finished Dosage Form.

There are two major types of lubricants: 1. Hydrophilic Generally poor lubricants, no glidant or anti-adherent properties. 2. Hydrophobic Hydrophobic lubricants are generally good lubricants and are usually effective at relatively low concentrations. Many also have both anti- adherent and glidant properties.

Of all the lubricants in use, magnesium stearate is the most widely used lubricant in the pharmaceutical industry. Although it is used in low concentrations, it is often the cause of many problems in solid oral dosage forms. Determining the concentration of lubricants use and mixing time are critical. If concentrations are too low, or distribution and mixing times are inadequate, problems can occurs, such as :

Punch filming Picking Sticking Capping Binding in the die cavity

If concentrations are too high, or distribution and mixing times are too great, other problems occurs :

Decrease in tablet hardness Inability to compress into tablets Increase in tablet disintegration times Decrease in rate of dissolution

HOW DO LUBRICANTS WORK? Magnesium Stearate: Magnesium (and calcium) stearate exists as plate-like crystals stacked together. As the blending process proceeds, plates continue to shear off and coat adjacent particles of granules, drug or other excipients. The higher the concentration of Magnesium Stearate used or the longer this blending continues, the more complete this coating of the adjacent particles will become.

What causes these problems? The hydrophobic coating interferes with wetting thereby leading to increases in the time required for the tablet to disintegrate and/or the drug to become dissolved. Additionally, a complete coating of lubricant may affect tablet hardness by interfering with the interparticle bonding required by formulations where tablets are formed with components that bond by plastic deformation. Magnesium stearate may also increase tablet friability Tablets formed by brittle fracture are less affected because brittle fracture produces clean unlubricated sites where bonding can occur during compression. Wet granulation formulations are also less affected (than direct compression formulations) since significant clean surfaces are formed during compression as the granules deform with shear to provide bonding sites. The use of Magnesium Stearate as a lubricant has further complications in that a variety of commercial samples have been known to exhibit significant batch-to-batch variation in their lubricant properties. Various physical properties of different batches of magnesium stearate, such as specific surface area, particle size, crystalline structure, moisture content, and fatty acid composition, have been correlated with

lubricant efficacy.Three factors have been determined to be mainly responsible for this variation: 1. Differences in chemical composition: Commercial Magnesium Stearate actually consists of a mixture of several different fatty acids. A composition consisting of Magnesium Stearate to palmitate in a ratio of 25% to 75% respectively is thought to be optimum for lubricity and shear properties. But this composition s not usually found in commercial samples. 2. Differences in specific surface area: Since the lubricating properties of magnesium stearate are related to its ability to coat other particles in a formulation during mixing, samples of a greater surface area should be able to do this more effectively. There is some argument about this however, since it is known that the surface area of magnesium stearate continually changes during blending as a result of its delamination. 3. Differences in crystal structure: Different crystalline structures have different strengths of attraction between adjacent lamellae thereby affecting its relative ability to delaminate and subsequently coat adjacent particles. Batches containing very low concentrations of these impurities have been shown to retard the dissolution of a drug to a greater extent than when using batches that contain higher levels of impurities. Due to variations in the specific surface area, the labeling states that specific surface area and the method specified for its determination should be listed on the label. Reduction in dissolution caused by the effects ofmagnesium stearate in some cases can be overcome by including a highly swelling disintegrant in the formulation.