Aggregate Elasticity, Crystal Structure, and Tableting Performance for p-Aminobenzoic Acid and a Series of Its Benzoate Esters.

Abstract

The tableting performance for p-aminobenzoic acid (PABA) and a series of its benzoate esters with increasing alkyl chain length (methyl-, ethyl-, and n-butyl) was determined over a broad range of compaction pressures. The crystalline structure of methyl benzoate (Me-PABA) exhibits no slip systems and does not form viable compacts under any compaction pressure. The ethyl (Et-PABA) and n-butyl (Bu-PABA) esters each have a similar, corrugated-layer structure that displays a prominent slip plane and improves material plasticity at low compaction pressure. The compact tensile strength for Et-PABA is superior to that for Bu-PABA; however, neither material achieved a tensile strength greater than 2 MPa over the compression range studied. Complementary studies with powder Brillouin light scattering (BLS) show the maxima of the shear wave, acoustic frequency distribution red shift in an order consistent with both the observed tabletability and attachment energy calculations. Moreover, zero-porosity aggregate elastic moduli are determined for each material using the average acoustic frequency obtained from specific characteristics of the powder BLS spectra. The Young's moduli for Et- and Bu-PABA is significantly reduced relative to PABA and Me-PABA, and this reduction is further evident in tablet compressibility plots. PABA, however, is distinct with high elastic isotropy as interpreted from the narrow and well-defined powder BLS frequency distributions for both the shear and compressional acoustic modes. The acoustic isotropy is consistent with the quasi-isotropic distribution of hydrogen bonding for PABA. At low compaction pressure, PABA tablets display the lowest tensile strength of the series; however, above a compaction pressure of ca. 70 MPa PABA tablet tensile strength continues to increase while that for Et- and Bu-PABA plateaus. PABA displays lower plasticity relative to either ester, and this is consistent with its crystalline structure and high yield pressure determined from in-die Heckel analysis. Overall the complementary approach of using both structural and the acoustic inputs uniquely provided from powder BLS is anticipated to expand our comprehension of the structure-mechanics relationship and its role in tableting performance.