Quantifying the intrinsic effects of lubrication to predict the tensile strength of pharmaceutical formulations

A new model was developed to predict the tensile strength of tablets compressed from a lubricated dry powder blend by characterizing each blend component’s lubrication behavior. The tabletability of conventional immediate release tablet diluents and model drugs was first determined using the approach reported by Vreeman and Sun (A powder tabletability equation, Powder Technology, 2022) to describe the relationship between compaction pressure (P) and tensile strength (σ). Then components were individually mixed with magnesium stearate at different lubricant loadings, particle sizes, and mixing extents.

The lubricated tensile strength data was modeled using a modification of the Kushner and Moore model (Scale-up model describing the impact of lubrication on tablet tensile strength, International Journal of Pharmaceutics, 2010) by adding a relative lubricant surface area parameter to account for lubricant loading and particle size. An excellent fit of the model to the data (R² = 0.99) was achieved for the individually lubricated diluents allowing for the determination of their respective lubricant sensitivity and rate constant values. The lubricated diluent tensile strengths were then applied in the power mixing law to predict the lubricated blend tensile strength.

Model predictions for more than 50 different lubricated binary or ternary diluent blends resulted in a strong correlation with the measured values (R² = 0.93). The model was finally tested by predicting the tensile strengths of formulations with active pharmaceutical ingredients (R² = 0.92). The new model can be used in computational assessments of blends and to assess multi-component lubricated tablet formulations during drug product design and optimization.

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Materials

Microcrystalline cellulose (MCC) (Avicel PH-102, FMC BioPolymer, Philadelphia, PA), spray-dried lactose monohydrate (Lac) (Fast Flo 316, Foremost Farms, Rothschild, WI), and dibasic calcium phosphate anhydrous (DCP) (A-Tab, Innophos, Cranbury, NJ) were selected as common tableting diluents. Three different particle size grades of magnesium stearate (MgSt) were studied as lubricants, including: small (S) (Vegetable (Light), Taihei Chemical Industrial Co., Osaka, Japan).

Allan Hutchins, Matthew P. Mullarney,
Quantifying the intrinsic effects of lubrication to predict the tensile strength of pharmaceutical formulations,
International Journal of Pharmaceutics, Volume 689, 2026, 126480, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2025.126480.