Compression Modulus and Apparent Density of Polymeric Excipients during Compression—Impact on Tabletability

Abstract

The present study focuses on the compaction behavior of polymeric excipients during compression in comparison to nonpolymeric excipients and its consequences on commonly used Heckel analysis. Compression analysis at compaction pressures (CPs) from 50 to 500 MPa was performed using a compaction simulator. This study demonstrates that the particle density, measured via helium pycnometer (ρpar), of polymeric excipients (Kollidon®VA64, Soluplus®, AQOAT®AS-MMP, Starch1500®, Avicel®PH101) was already exceeded at low CPs (<200 MPa), whereas the ρpar was either never reached for brittle fillers such as DI-CAFOS®A60 and tricalcium citrate or exceeded at CPs above 350 MPa (FlowLac®100, Pearlitol®100SD). We hypothesized that the threshold for exceeding ρpar is linked with predominantly elastic deformation. This was confirmed by the start of linear increase in elastic recovery in-die (ERin-die) with exceeding particle density, and in addition, by the applicability in calculating the elastic modulus via the equation of the linear increase in ERin-die. Last, the evaluation of “density under pressure” as an alternative to the ρpar for Heckel analysis showed comparable conclusions for compression behavior based on the calculated yield pressures. However, the applicability of Heckel analysis for polymeric excipients was questioned in principle. In conclusion, the knowledge of the threshold provides guidance for the selection of suitable excipients in the formulation development to mitigate the risk of tablet defects related to stored elastic energy, such as capping and lamination.

Using Chia Powder as a Binder to Obtain Chewable Tablets Containing Quinoa for Dietary Fiber Supplementation

“…The formulations that exhibited exceptional flow properties, with a value of <15%, were T8, T7, and T6. The other formulations had a reasonable flow rate, or assistance was required, which, in both cases, can be solved with the addition of excipients that help with the fluidity of the powder, for example, a rheology promoter such as silicon dioxide [41]; a diluent to aid filling and compressibility such as microcrystalline cellulose, lactose, or co-processed products [42]; and lubricants such as magnesium stearate [43].…”

Use of Chia as a Binder to Obtain Chewable Tablets Containing Quinoa for Dietary Fiber Supplementation

“…The formulations that exhibited exceptional flow properties, with a value of < 15%, were R8, R7, and R6, respectively. The other formulations have a reasonable flow rate or assistance is required, which in both cases can be solved with the addition of excipients that help with the fluidity of the powder, for example, a rheology promoter such as silicon dioxide [35], a diluent to aid filling and compressibility such as microcrystalline cellulose, lactose or co-processed products [36], and lubricants such as magnesium stearate [37].…”

Sample Size Requirements of a Pharmaceutical Material Library: A Case in Predicting Direct Compression Tablet Tensile Strength by Latent Variable Modeling

“…Composition A has two levels, representing two pharmaceutical excipients (i.e., microcrystalline cellulose PH102, lactose Tablettose ® 80). The MCC PH102 and lactose Tablettose ® 80 are two commonly used diluents in tablet formulation, and they represent the plastic and brittle compaction behaviors, respectively[49][50][51]. MCC PH102 was classified into Category 1 tabletability, and lactose Tablettose ® 80 was classified into Category 2B by the index d. Composition B has four levels, representing 4 natural production powders (i.e., Stellariae Radix extract, Radix Rehmanniae Preparata extract, Rhizoma Alismatis extract, and Flos Farfarae extract).…”