Influence of elastic deformation of particles on Heckel analysis.
The Heckel equation is one of the most useful equations for describing the compaction properties of pharmaceutical powders. Important material properties (e.g., yield strength) of powders can be derived using Heckel analysis. Two types of Heckel analysis are in common use. One is the "out-of-die," or "zero-pressure" method, the other is the "in-die" or "at-pressure" method. Because particles undergo elastic deformation under pressure, which tends to lower the porosity of the powder bed, the "out-of-die" method describes powder consolidation and compaction more accurately than the "in-die" method. However, "in-die" Heckel analysis has been widely used because of the speed and ease of data collection. Using L-lysine monohydrochloride dihydrate as a model compound, this work analyzes quantitatively the effects of elastic deformation on the calculation of porosity of a tablet, and therefore on the Heckel analysis. The effects of a small change in porosity, epsilon, on Heckel analysis are presented mathematically. It is found that a decrease in porosity of 0.001, when the porosity is lower than 0.05, causes a significant increase in the value of -ln epsilon. Therefore, data at epsilon < 0.05 should be interpreted with caution when using Heckel analysis. Elastic deformation causes positive deviations in the Heckel plot, and therefore leads to a yield strength that is lower than the true value. The lower the elastic modulus of the powder, the greater is the deviation from the true value. Therefore, the "in-die" method gives values of yield strength that are significantly lower than the true values for most pharmaceutical powders.
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Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455-0343, USA.
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D004548:Elasticity; D008433:Mathematics; D011208:Powders; D011312:Pressure; D013678:Technology, Pharmaceutical
D011208:Powders