Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Pentoxifylline (PTX) is a xanthine drug that acts as a nonspecific inhibitor of phosphodiesterase with rapid dissolution and absorption in the body, given its high solubility in aqueous media. Due to that, PTX requires modulation of its release through sustained dosage forms. However, none of these formulations cater to reducing the solubility, controlling the dissolution rate, and giving rise to a longer half-life of PTX, extending the in vivo retention time. This work employs crystal engineering to systematically investigate how coformer selection governs PTX’s dissolution behavior through structure–property relationships. Five novel solid forms were produced by mechanochemical activation (PTX with caffeic, citric, glutaric, and vanillic acid). The new structures were elucidated by X-ray diffraction techniques and were characterized by spectroscopic and thermal methods. The physicochemical (solubility and melting point) and structural (crystal packing) properties were carefully investigated. Combined with two reproduced reported systems (salicylic/benzoic acids), we identify key structural motifs─particularly R 2 2 (8) carboxylic acid···N-heterocycle synthons─that correlate with solubility modulation and dissolution assays. While one novel cocrystal showed reduced solubility, the results provide design criteria for tuning PTX formulations, with mechanistic insights applicable to xanthine derivatives.
Source: Crystal Growth & Design
Authors: J. C. Fonseca, S. G. C. Fonseca, A. P. Ayala
Institution: Universidade Federal do Ceará
Language: English
Subfield: Physical and Theoretical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Award: G3690646728
OpenAlex ID: W4416380257