1. Tautomerisation and polymorphism in molecular complexes of piroxicam with mono-substituted benzoic acids
Craig Wales, Lynne H. Thomas and Chick C. Wilson*. CrystEngComm, 2012, 14, 7264–7274
The work reported here is part of a wider investigation into the tautomerism of piroxicam, in which it has been found that co-crystallisation of piroxicam with mono-substituted benzoic acids
(BAs) produces molecular complexes where the tautomer formed varies depending on the benzoic acid used. Of particular interest are the piroxicam complexes with each of 2-, 3-, and
4-fluorobenzoic acids (FBAs) which all exhibit the rare phenomenon of tautomeric polymorphism. The crystal structures are presented here, along with their analysis from a crystal engineering perspective and attempts to rationalise the observed hydrogen bonding (H bonding) patterns.
2. Water-soluble gold nanoparticles based on imidazolium gemini amphiphiles incorporating Piroxicam
Mafalda Rodrigues, Ana C. Calpena, Lluısa Perez-Garcıa*. RSC Adv.,2014, 4,9279–9287
The model drug used was piroxicam (Fig. 1), which is a poorly water soluble drug, used extensively in cases of arthritis and osteoarthritits for its anti-inflammatory activity, as well as in cases of colorectal cancer due to its preventive properties. Piroxicam is an acidic molecule, but acidity is attributed to the enolic group and not to a carboxylate group (as was the case in our previous work), and its binding to gold nano-particles coated with imidazolium amphiphiles had yet to be proven. Thus, extraction of piroxicam from an organic (dichloromethane) solution to the aqueous phase, containing the water soluble 1.GNP, was performed.
3. Intermolecular hydrogen transfer and solubility tuning in multi-component molecular crystals of the API piroxicam
Lynne H. Thomas, Anneke R. Klapwijk, Craig Wales and Chick C. Wilson*. CrystEngComm,2014, 16, 5924–5932
In the solid state, piroxicam has previously been shown to exist in two ionisation states when not in its neutral form. While pure piroxicam exists in the non-ionised form in the solid state, it has been shown that in polar solvents, such as acetonitrile which is commonly used in crystallisation experiments with piroxicam, the zwitterionic form is present in large quantities. The formation of the zwitterion, through intramolecular hydrogen-transfer, has been observed in solvates and multi-component molecular crystals of piroxicam in almost equal numbers to molecular complexes including neutral piroxicam. On the other hand, intermolecular hydrogen transfer has been observed in only one piroxicam complex, with ethanolamine (1 : 1, pKa = 9.5), forming a salt with a piroxicam anion (PX−).
4. Hydrogen bonding effects in the photophysics of a drug, Piroxicam, in homogeneous media and dioxanewater mixtures
Suzana M. Andrade and Slvia M. B. Costa*. Phys. Chem. Chem. Phys., 1999, 1, 4213È4218
The same must occur with Piroxicam according to its spectroscopic behaviour where hydrogen bonds seem to play a key role. Further attempts to relate the strength of the intramolecular hydrogen bond and the photochemical stability were made. Although it is clear now that ESIPT alone cannot account for all the effects of photostability, it certainly does play a crucial role, as can be envisaged from the ensemble of our data. This also, is reinforced by the fact that Piroxicam is administered to the patients in a composition that involves cyclodextrin, where it is known that the molecule adopts the closed conformation.