US EPA

1611642 

Journal Article 

Solubility Advantage of Tenoxicam Phenolic Cocrystals Compared to Salts 

Bolla, G; Sanphui, P; Nangia, A 

2013 

Yes 

Crystal Growth & Design
ISSN: 1528-7483
EISSN: 1528-7505 

13 

5 

1988-2003 

10.1021/cg4000457 

WOS:000318468400024 

Tenoxicam (TNX) belongs to the Amin family of drugs
popularly known as nonsteroidal anti-inflammatory drugs (NSAIDs). Its therapeutic action as a
drug is limited by poor aqueous solubility (14 mg/L). Here, we report cocrystals of TNX with
benzoic acid, salicylic acid, catechol, resorcinol, pyrogallol, and salts with piperazine, HCl,
and methanesulfonic acid and solvates with formic acid, acetic acid, propionic acid, and
nitromethane. All the new solid phases (cocrystals and salts) were characterized by infrared
spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and confirmed by
single crystal X-ray diffraction. Tenoxicam exists in the zwitterionic form in its stable
crystalline form, as well as all the novel adducts reported in this study. The crystal
structures, are assembled via O-H center dot center dot center dot O- hydrogen bonds further
assisted by weaker C-H center dot center dot center dot O interactions. This is the first report
of oxicam cocrystals with phenols to our knowledge. Solubility and intrinsic dissolution rate of
TNX cocrystals/salts were carried out to optimize the solid form with the best physicochemical
properties. Tenoxicam-resorcinol (1:1) cocrystal exhibited the highest solubility (10-fold
compared to the API), and moreover it was stable for up to 24 h in the slurry crystallization
conditions of pH 7 phosphate buffer (neutral) and pH 1.2 medium (acidic). Tenoxicam-piperazine
(1:0.5) salt is stable for 24 h in the slurry medium of the pH 7 buffer and exhibited 5.5 times
higher solubility than tenoxicam. The other cocrystals dissociated slowly while the HCl and
mesylate salts dissociated completely to tenoxicam within the same duration. TNX-benzoic acid and
TNX-salicylic acid cocrystals were stable for up to 24 h in slurry conditions of pH 1.2 but in pH
7 medium they slowly converted to TNX after 24 h.