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Tablets must deliver accurate dosesof active pharmaceutical ingredients(APIs)—typically verified by dissolu-tion testing—and that requires scruti-nizing the function and effectivenessof every tablet excipient, includingmagnesium stearate. Magnesiumstearate acts as a lubricant, helpingpowder formulations flow and pre-venting tablets from binding in the dieand sticking to the upper punch. Itseffectiveness as a lubricant has mademagnesium stearate the most commonexcipient in tablets, but it has draw-backs. Perhaps the most serious ofthese is its slowing of dissolution,which may compromise delivery ofthe API. This, among other reasons,has led the pharmaceutical industry toseek alternatives.

Magnesium stearate has a plate-likestructure that shears easily, enabling itto reduce friction between the die walland the tablet’s edge during compres-sion and ejection. The excipient alsoreduces the amount of force that thepunch must apply to compress andeject the tablet. Furthermore, itreduces stress on the tablet and thetablet press by preventing the tabletfrom binding in the die and sticking tothe upper punch. Magnesium stearatealso increases the density of the pow-der bed before compression and tendsto equalize pressure distribution withinthe tablet. Both functions promoteuniform tablet density, which pro-motes uniform bioavailability.

There are drawbacks, however, tothe use of lubricants in powder blends.The lubricant may form a barrieraround particles that remains intactduring compression, making thetablets hydrophobic and prolongingdissolution times. Lubricants may alsointerfere with particle bonding,thereby decreasing blend cohesive-ness, which is why lubricants arealways blended into formulations justprior to tabletting: to minimize theirnegative effects. This extra blending

step takes time and ties up equipment,and there are costs associated withthat. It also hampers the adoption ofcontinuous processing. Furthermore,the amount of lubricant added (typi-cally 0.5 to 2.0 percent w/w) tends toexceed what’s needed to make a goodtablet, which can lead to prematuretooling wear because achieving thedesired tablet hardness will requiremore compressive force.

Alternatives to adding lubricantsto the blend. Since the 1960s, thepharmaceutical industry has developedseveral methods that reduce, if noteliminate, the need to add lubricantsto powder blends. These include usingoil as a lubricant, using PTFE (Teflon)inserts on the tooling, and adding spe-cialty treatments (coatings) to thetooling. While each of these methodsshowed some success, they also hadtechnical limitations and/or were ex-pensive. The most promising alterna-tive was external lubrication.

The first systems to provide exter-nal lubrication (lubrication of thetooling during compression) appearedin the 1990s. They used two nozzlesto continuously spray dry magnesiumstearate onto the punch heads and diewalls prior to the filling stage; thus,only a small amount of lubricantreached the tablet. These nozzles,however, tended to get blocked, sothey were heated, which partiallyovercame the problem. But becausethe spray was continuous, other prob-lems developed: Too much magne-sium stearate was consumed; thetablet press became “foggy” with dust;and it was difficult to measure and val-idate how much lubricant each tabletcontained.

Despite these drawbacks, the phar-maceutical industry remained inter-ested in external lubrication, and bet-ter systems were developed, includinga system called AccuSpray that ourcompany introduced in 2007. Itapplies an intermittent spray of mag-

nesium stearate suspended in a 10 per-cent solution of pure ethanol. The sus-pension is applied to the upper andlower punches and the die wall usingtwo piezo valves activated by a prox-imity sensor. The amount of magne-sium stearate applied is minimal, typi-cally 0.03 percent w/w of the tablet.Furthermore, the amount can be mea-sured and validated. Ethanol consump-tion is typically 250 milliliters per houron a tablet press operating at 100,000tablets per hour; no ethanol residueremains on the tablet. Other advan-tages of external lubrication includetablets that are harder than those withblended lubricants and shorter dissolu-tion times. The system also reduceslubricant consumption.

While external lubrication doesn’teliminate magnesium stearate, reduc-ing it is a good first step, and it’s pos-sible that other alternative means oflubricating the tablet press will be-come available. In fact, many of uswelcome the day when magnesiumstearate is no longer needed at all.

T&C

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Nic Michel is vicepresident, process divi-sion, atOystarUSA,Edison, NJ. Tel. 732343 7600, fax 732343 7601. Website:www.oystarusa.com.The division offersManesty tablet pres-ses and coaters andHüttlin granulators,dryers, and coaters.Dipankar Dey ishead of processing andvalidation forOystar’sManesty unit.

b a c k p a g eEliminating magnesium stearate from tablets