Lubricants in Pharmaceutical Solid Dosage Forms

Lubrication plays a key role in successful manufacturing of pharmaceutical solid dosage forms; lubricants are essential ingredients in robust formulations to achieve this. Although many failures in pharmaceutical manufacturing operations are caused by issues related to lubrication, in general, lubricants do not gain adequate attention in the development of pharmaceutical formulations. In this paper, the fundamental background on lubrication is introduced, in which the relationships between lubrication and friction/adhesion forces are discussed. Then, the application of lubrication in the development of pharmaceutical products and manufacturing processes is discussed with an emphasis on magnesium stearate. In particular, the effect of its hydration state (anhydrate, monohydrate, dihydrate, and trihydrate) and its powder characteristics on lubrication efficiency, as well as product and process performance is summarized. In addition, the impact of lubrication on the dynamics of compaction/compression processes and on the mechanical properties of compacts/tablets is presented. Furthermore, the online monitoring of magnesium stearate in a blending process is briefly mentioned. Finally, the chemical compatibility of active pharmaceutical ingredient (API) with magnesium stearate and its reactive impurities is reviewed with examples from the literature illustrating the various reaction mechanisms involved.

**Table 4.** The optimal concentration of commonly used lubricants for preparing solid dosage forms.
Water soluble lubricant	Amount in formulation (%)	Water insoluble lubricant	Amount in formulation (%)
Boric acid	1	Metal (Mg, Ca, Na) stearate	0.25–2
Carbowax (PEG) 4000/6000	1–5	Stearic acid	0.25–2
Sodium oleate	5	Sterotex	0.25–1
Sodium benzoate	5	Talc	1–5
Sodium acetate	5	Waxes	1–5
Sodium lauryl sulfate	1–5	Stear-O-Wet	1–5
Mg-Lauryl sulfate	1–2	Glyceryl behenate (Compritol 888)	0.5–3

Conclusions

In this paper, the fundamentals of lubrication and the action mechanisms of lubricants in typical pharmaceutical manufacturing processes have been reviewed; the role of lubricants in improving pharmaceutical operations by reducing the adhesion forces between powder/equipment as well as particle/particle in terms of wall friction and inter-particle friction has been summarized. In addition to other classes of lubricants used in the pharmaceutical industry, magnesium stearate as the most frequently used lubricant has been discussed in detail. Furthermore, the lubrication efficacy of hydrates of magnesium stearate and their effect on the performance of formulations in pharmaceutical operations were discussed. Overall, it was concluded that the dihydrate of magnesium stearate is the best hydration state for lubrication. In terms of the effect of lubricant particle size, magnesium stearate with a large surface area and small particle size has the best lubrication efficiency, but it reduced the hardness of tablets and caused slow-down of dissolution. Moreover, the lubricant significantly affects the dynamic process of compaction/compression and the mechanical properties (solid fraction and tensile strength) of ribbons as well as tablets due to the improved flowability of the lubricated blends. For adequate lubrication, on-line monitoring can help to determine the end-point of a blending process, and the distribution of lubricant as well as its composition. Finally, magnesium stearate and its impurities often cause chemical instability of APIs. In selection of a lubricant for a formulation many factors including chemical instability, physical incompatibility, and lubrication efficiency should be considered.

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Continue reading the full article: Li, J.; Wu, Y. Lubricants in Pharmaceutical Solid Dosage Forms. Lubricants 2014, 2, 21-43. https://doi.org/10.3390/lubricants2010021