Structural characterization of two polymorphic forms of piroxicam pivalate

Abstract

The crystal and molecular structures of two polymorphs of piroxicam pivalate are presented and discussed. A peculiarity of the high melting (154 degrees C) polymorph is the association of piroxicam pivalate molecules as centrosymmetric dimers by hydrogen bonding. Two centrosymmetrically related N-H...N hydrogen bonds maintain the dimer structure involving the amido nitrogen atom as donor and the pyridine nitrogen atom as acceptor. Molecular association of this type does not occur in the crystal structures of drugs belonging to the oxicam class of nonsteroidal antiinflammatory drugs. Two distinct conformations coexist in the crystal of the low melting polymorph (136 degrees C) with differing hydrogen bonding arrangements within domains of the crystallographically independent molecules. The occurrence of different molecular conformations (conformational polymorphism) associated with different hydrogen bonding schemes in discrete domains is an unusual structural feature. Structural data for the two polymorphs are also correlated with the relevant infrared spectra. Computer-generated X-ray powder diffraction patterns for the two polymorphs of piroxicam pivalate are in very good agreement with the experimental ones, thus confirming the validity of the single-crystal X-ray models.

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“…The conformational polymorphisms of the two forms of piroxicam pivallate have been described in literature 19 . The inclusion of different solvent molecules in a crystal lattice can lead to the existence of different packing pattern, and has also been found to influence the molecular conformation of paroxetine HCl in two solvate forms 20 .…”

Solid State Characterization of E2101, A Novel Antispastic Drug

“…These properties can impact on the rational design of a pharmaceutical dosage form, the optimization of a manufacturing process,1,2 and the bioavailability of the drug 3–5. Therefore, polymorphism of pharmaceutical molecules,6–10 including excipients such as D‐mannitol,11 has been a source of interest for many years, and various methods to evaluate the polymorphism have also been reported 12–14. If the existence of several crystal forms and transformation behavior were discovered as soon as possible, the term and the cost of drug discovery and development could be reduced.…”

Pathways of Biotransformation — Phase I Reactions

“…Upon oral administration, pivampicillin displays a better absorption than ampicillin, ensuring superior plasma concentrations, at equivalent doses [159,160] (See also Chapter 9). Analogously, the ester of piroxicam with pivalic acid is an effective prodrug with activity comparable to that of the parent drug but with fewer of the ulcerogenic effects that are associated with the carboxyl group of the parent compound [161]. Another, but older example of a prodrug in this drug class is ampiroxicam derived by conversion of the parent drug to an ethyl carbonate ester [162].…”