Polymorphism in Piroxicam

Abstract

Piroxciam is a polymorphic drug. However, reports on the number and nomenclature of the polymorphs of piroxicam and the complete hydrogen-bonding patterns of piroxicam molecules in the crystal forms are in conflict and are sources of confusion, which we attempt to clarify. The difference in energy of the two polymorphs, I and II, of piroxicam arises predominantly from the difference between their lattice energies, rather than between their conformational energies. The detailed hydrogen-bonding networks of the two polymorphs are described and compared. Despite stabilization of the polymorphs by hydrogen bonds, a loss of polymorphic memory was observed upon cryogrinding the two polymorphs, leading to differences in recrystallization behavior between amorphous piroxicam prepared from polymorphs I and II.

A comparison of the experimental and theoretical charge density distributions in two polymorphic modifications of piroxicam

“…Since then, the polymorphism of piroxicam has been widely investigated leading to identification of a total of four anhydrous forms and one monohydrate form of piroxicam. While there have been significant efforts devoted to the discovery of the polymorphs of piroxicam, the characterisation and nomenclatures of piroxicam polymorphs have remained inconsistent and occasionally conflicting 3 .…”

Formation, Physical Stability, and Quantification of Process-Induced Disorder in Cryomilled Samples of a Model Polymorphic Drug

“…12 This process represents an effective method of reducing the risk of recrystallisation of any amorphous materials produced due to the lower process temperatures involved compared to milling at ambient or higher temperatures, and it is often a more efficient way to prepare an amorphous API for those compounds which are disordered by milling. [13][14][15][16][17] Amorphous drugs are important as their greater surface area and surface activity can lead to higher bioavailability 18,19 and attempts have also been made to use the amorphous form of a drug to circumvent patents which apply to a crystalline form. 20 However, due to the metastable nature of amorphous drugs, the amorphous regions or crystal defects created by milling are unstable and under a range of circumstances such as elevated temperature or relative humidity, they undergo structural changes or revert to the original form or to other stable crystalline forms.…”

Use of Drifts and PLS for the Determination of Polymorphs of Piroxicam Alone and in Combination with Pharmaceutical Excipients: A Technical Note

“…The identities of both polymorphic forms were confirmed by comparing their X-ray diffraction (XRD) patterns with those previously reported (2,3). KBr was obtained from Sigma (Sigma-Aldrich, St. Louis, MO, USA).…”

“…Crystalline piroxicam is polymorphic and exists in various crystalline forms designated as form I, form II, form III, and monohydrate form. Form I is also named β, cubic form, and form A, meanwhile form II is termed α, α1, α2, needle form, and form B (2,3). Form III is thermally unstable and can be converted to form II and form I, respectively (2).…”