Drug-Drug Coamorphous System of Tadalafil and Finasteride for Enhanced Pharmaceutical Performance

We report a modified bicomponent solid-state form of tadalafil (TDF) and finasteride (FNS), prepared at a 1:1 molar stoichiometric ratio, corresponding to the USFDA-approved combination marketed under the trade name Entadfi, for the treatment of benign prostatic hyperplasia. Individually, both constituent drugs suffer from the limitation of low aqueous solubility, belonging to class-II of the biopharmaceutical classification system. A drug-drug coamorphous system of TDF and FNS was prepared by mechanochemical synthesis. Characterization of this novel phase was carried out by powder X-ray diffraction, thermal analysis, and FT-IR spectroscopy. Particle characteristics and morphological features of the coamorphous system were studied by scanning electron microscopy and 3D-laser scanning microscopy. Possible intermolecular interactions between TDF and FNS, facilitating the formation of the coamorphous phase, as indicated by spectroscopic analysis, were validated by the computational study employing density functional theory. Interestingly, in vitro dissolution studies showcased significant improvement in the dissolution profile of the coamorphous system compared with the physical mixture, which was successfully translated to the in vivo study in SD rats. Physical stability of the developed coamorphous system evaluated under accelerated as well as long-term stability conditions indicated reasonable stability for potential drug product usage. Considering its industrial applicability due to obvious benefits, viz., single solid phase, improved solubility, dissolution, and better pharmacokinetic parameters leading to higher bioavailability, the developed coamorphous system could prove to be a better therapeutic alternative over the marketed physical mixture.