Novel solid forms of oxaprozin: cocrystals and an extended release drug–drug salt of salbutamol

Abstract

Oxaprozin (OXP) is a non-steroidal anti-inflammatory drug mainly used to relieve the inflammation, swelling, and joint pain associated with osteoarthritis and rheumatoid arthritis. OXP shows poor aqueous solubility (0.0325 mg mL⁻¹) that limits its bioavailability. The current study was aimed at identifying novel solid forms that could impact the physicochemical properties of OXP. Our solid form screening resulted in cocrystals with 4,4′-bipyridine and 1,2-bis(4-pyridyl)ethane and molecular salts with piperazine, 2-amino-3-picoline, and an antiasthmatic drug, salbutamol (SAL). Differential scanning calorimetry and X-ray diffraction techniques were employed to characterize the salts and cocrystals, and stability of the pharmaceutically acceptable salts was evaluated by storing at accelerated test conditions and slurry and dynamic vapour sorption techniques. Evaluation of the solubility and dissolution rate of piperazine and SAL salts revealed a modest effect of salt formation on the physicochemical properties of the OXP. The OXP⁻–SAL⁺–H salt provides an alternative solution to the short half-life of existing SAL formulations, which need to be dosed frequently to maintain therapeutic plasma levels. The drug–drug salt dissolves much slower compared to SAL and could potentially be developed as controlled release formulations of SAL. In addition, the presence of OXP as an integral part of the molecular salt enables exploitation of the molecular salt as a novel composition for development of combination drug therapy for treating inflammation associated with asthma.