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.
In
this report caffeine (CAF) co-crystallization with a fluoro-nitrobenzoic
acid (F-NBA) yields a new solid form with superior tableting performance.
A primary N···H–O synthon connects the basic
nitrogen of CAF with the carboxylic acid of F-NBA to result in a layered
structure with supportive CH3···O interactions.
Over the entire compaction pressure range of nominally 50–300
MPa, the co-crystal displayed improved tensile strength relative to
the individual co-formers that demonstrated tensile strengths consistently
below 2 MPa. Qualitatively we interpret this tableting improvement
for the co-crystal a result of increased plasticity manifested from
the layered co-crystal structure, an observation consistent with previous
co-crystal studies on modified material mechanics that suggest facile
slip plane activation supports improved tableting. Powder Brillouin
light scattering (BLS) is further introduced as a novel tool to rapidly
evaluate elastic anisotropy to complement our structural interpretation
of tableting performance. Each powder BLS spectra revealed two acoustic
frequency distributions that we assign as longitudinal and transverse
and permits rank-order of the elastic anisotropy. The shear mode distribution
revealed an increasing population of low-velocity modes that mirrored
the rank-order tableting performance of CAF:F-NBA > CAF > F-NBA.
With
further experimental support, we anticipate powder BLS may be utilized
as a complementary tool to quantify and discriminate the mechanical
properties of co-crystals and polymorphs for relation to their processing
performance.
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