This study investigated the effects of polymeric additives such as hydroxypropyl methyl cellulose (HPMC) and polyvinylpyrrolidone (PVP) on the growth kinetics of naproxen crystal, a model poorly water-soluble active pharmaceutical ingredient. These additives are commonly used in pharmaceutical formulations to stabilize fine crystalline suspensions and amorphous solid dispersions. Measurement of seed crystal growth rate in ethanol–water solution as a function of supersaturation suggested a spiral growth mechanism, with the b (needle) axis growth rate five times faster than the c-axis growth rate at 40% relative supersaturation. At nearly equivalent supersaturations, growth along the b-axis was completely inhibited at one end of the seed crystal in the presence of either of the two polymeric additives. In contrast, growth at the other end of the b-axis was significantly accelerated in the presence of PVP. Molecular modeling revealed preferential interaction of the additives with the {011} faces of naproxen crystal, consequently leading to selective growth inhibition along the +b axis. This simulation result is consistent with the asymmetrical crystal growth observed experimentally. Growth promotion in the −b direction of naproxen crystal (in the presence of PVP alone) was explained based on hydrophobic–hydrophilic intermolecular interactions occurring at the crystal–solution interface. In the light of these findings, the use of polymeric additives, either singly or in combination, to modulate naproxen crystal shape and size was further explored.

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Precipitation of paraffin wax (long-chained n-alkanes) from engine oil and fuel distillates at low temperatures is generally prevented using low-dosage polymeric additives, known as pour point depressants (PPDs). The ability of a PPD to inhibit wax crystallization is largely determined by how well its alkyl side chains interact with the waxy components present in the base oil. The current study aims to elucidate the mechanism underpinning this structure–property relationship using docosane (n-C22H46) dissolved in a mixture of dodecane and toluene as a model waxy oil and the homologous series of paraffins as “tailor-made” additives. By determining the wax crystal nucleation kinetics using polythermal turbidimetry measurements, a direct link between the carbon chain length of the additive molecule and its ability to retard wax precipitation was established. Thermodynamic and structural analysis of the wax formation process using differential scanning calorimetry and small/wide-angle X-ray scattering techniques respectively revealed that the additive incorporates into the lamellar wax aggregates formed during the nucleation stage and subsequently impedes its crystallization. This mechanism is consistent with the cocrystallizing behavior of n-alkanes from multiparaffinic solutions to form a solid solution. Only additives with alkyl chains longer than the solute wax retarded nucleation and growth along the needle axis of the wax crystal because of the end-chain protrusion/bending disorder in the resultant lamellar wax crystal structure.