Effect of chirality on PVP/drug interaction within binary physical mixtures of ibuprofen, ketoprofen, and naproxen: A DSC study

Abstract

We report on the thermal behavior of freshly prepared binary drug/polymer physical mixtures that contained ibuprofen, ketoprofen, or naproxen as a drug, and polyvinylpyrrolidone (PVP), hydroxyethylcellulose (HEC), or methylcellulose (MC) as excipient. At 6-10 degrees C/min heating rates the DSC detected a sharp, single endotherm that corresponds to the melting of drug. On heating physical mixtures of PVP and racemic ibuprofen or ketoprofen at lower heating rates, another endotherm was registered in front of the original one. To observe the additional endotherm, specific minimal values of the heating rate and of PVP weight fraction were needed; for ibuprofen and ketoprofen they were 1.5 and 2.0 degrees C/min, and 5 and 15% (w/w), respectively. At greater PVP weight fractions the top temperatures, T(mp), of both peaks were reduced almost linearly indicating strong solid-state interfacial reaction between the drug particles and PVP matrix. The additional endotherm was abolished at greater heating rates (2 degrees C/min for ibuprofen, 3 degrees C/min for ketoprofen), by replacing the racemate with respective S+-enantiomer and by replacing PVP with HEC and MC. Hence, the possible inclusion of enantioselective component within the PVP/drug interaction, responsible for the amorphization of physical mixture over storage, is assumed.

Mangosteen pericarp extract embedded in electrospun PVP nanofiber mats: physicochemical properties and release mechanism of α-mangostin

“…62 Below the T g , PVP was able to induce amorphization of ibuprofen in a physical mixture over the storage time. 60 In our study, conversion into amorphous state most probably occurred during the electrospinning process although the environment temperature was below the T g of PVP. The applied voltage caused the drug/polymer solution to rapidly migrate from the needle tip to the collector.…”

“…27 The XRD patterns of the MPE and PVP:MPE nanofiber mats suggested a crystalline-to-amorphous transformation of MPE, as indicated by the absence of crystalline peaks of the MPE in the MF1, MF2, and MF3 nanofiber mats. Note that PVP was reportedly capable of converting drug powder from crystalline state to amorphous state, particularly hydrophobic non-steroid anti-inflammatory drugs including indomethacin, ketoprofen, naproxen, and ibuproxam, [59][60][61][62] in a binary system generated from co-milling, hot melt extrusion, or other mixing processes under a certain environment where PVP is in rubbery state (above the glass transition point, T g ). [60][61][62] The degree of amorphization was dependent on the PVP content and the mechanism of amorphization involved loosening of crystal structure during exothermic mixing process, followed by dispersion in amorphous PVP chains and stabilization by intermolecular hydrogen bond between drug and PVP.…”

Development and Characterization of Amorphous Nanofiber Drug Dispersions Prepared Using Pressurized Gyration

“…Literature evidence (using IR and carbon 13 nuclear magnetic resonance ( 13 C NMR) and DSC) supports the occurrence of a solid-state interaction between IBU and PVP resulting in the formation of a stable glass-like form after storage. This interaction is thought to occur due to the formation of an intermolecular hydrogen bond between the free COOH group of IBU and the CO group of PVP …”

“…ATR-FTIR experiments were conducted on starting materials (IBU and K90F), IBU-K90F PMs, K90F PG fibers, and PG fibers to identify any differences in physical structure as well as evidence of molecular interaction by way of hydrogen bonding between IBU and K90F. Indications of strong hydrogen bonding between IBU and PVP have been reported in the carbonyl region (CO stretching) of IBU (∼1700 cm –1 ) and at the amide region (cyclic amide CO stretching) of K90F (∼1666 cm –1 ). − Figure shows ATR-FTIR spectra of IBU, K90F, IBU-K90F PMs, and PG fibers at the carbonyl region (CO stretching) of IBU and the amide region (cyclic amide CO stretching) of K90F. ATR-FTIR spectra of IBU-K90F 10% PM identified an irregularly shaped band overlapping between ∼1660 cm –1 and 1700 cm –1 (both the cyclic amide of K90F and carbonyl region of IBU).…”

Preparação, caracterização e estudo de dissociação do naproxeno em uma matriz de quitosana

“…Nesse estudo buscaram verificar o efeito da quiralidade na interação desta mistura. [15] Esses trabalhos destacam-se entre outros, que tem como base a interação do naproxeno com outras moléculas. Japão.…”