Stereoselective Disposition of Sustained Release Microspheres of Ibuprofen Enantiomers in Rats: II. Acute Gastrointestinal Toxicity

Janjikhel, Rajiv K.; Bricker, J. Douglas; Borochovitz, Dennis; Adeyeye, Christianah Moji

doi:10.1080/107175499266913

Cited by 4 publications

(1 citation statement)

References 27 publications

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“…Owing to the asymmetric carbon atom in the α position, profens are chiral compounds that can appear as the (+) and (-) antimers. The prevalent conviction in the pharmaceutical world is that, in vivo, the (+) antimers of profens exert a much more potent anti-inflammatory effect than their respective (-) counterparts [4][5][6][7][8][9]. Besides, in the past three decades or more, many reports have appeared on the relative ease of the in vivo chiral conversion of (+) profens to their (-) antimers and vice versa.…”

Section: Introductionmentioning

confidence: 99%

On ups and downs by analysis of profen drugs. A mini review

Sajewicz

Kowalska

2012

Acta Chromatographica

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Summary. Drug analysis is among the most sensitive areas of chemical analysis, simply because of its relevance to human health. Profens make the most important group of nonsteroidal anti-inflammatory drugs (NSAIDs), and in many countries some of them are freely sold over the counter. The in vitro liquid chromatographic analysis of profen drugs faces certain not commonly recognized yet acute and often impassable problems, due to the specific physicochemical properties of these compounds. In this mini review, we share our experience on the practical failures with the enantioseparation of profen drugs both by means of chiral planar and column chromatography. By use of such analytical techniques as polarimetry, 1 H and 13 C NMR spectroscopy, and mass spectrometry, we point out objectively the reasons that make liquid chromatographic enantioseparation of profens an almost impossible task. These compounds have an inherent ability (both in aqueous and nonaqueous solutions) to undergo oscillatory chiral conversion and oscillatory condensation, combined with a highly pronounced gelating ability. In our view, the oscillatory chiral conversion of profens questions the credibility of widespread claims on the superiority of the curative potential with the (+)-profens over that of the respective (-)-antimers (although the rightfulness of such claims cannot be dismissed, as the in vivo and in vitro behavior of many drugs are known to sometimes fundamentally differ). Moreover, it seems highly probable that, due to their highly pronounced gelating property, profen drugs can easily clog the blood vessels and thereby jeopardize living organisms.

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Section: Introductionmentioning

confidence: 99%

On ups and downs by analysis of profen drugs. A mini review

Sajewicz

Kowalska

2012

Acta Chromatographica

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Optimization and characterization of novel sustained release supermicro-pellet based dry suspensions that load dexibuprofen

Xia

Li²,

et al. 2020

Journal of Drug Delivery Science and Technology

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Application of Thin-Layer Chromatography to Investigate Oscillatory Instability of the Selected Profen Enantiomers in Dichloromethane

Sajewicz¹,

Piętka²,

Pienak³

et al. 2005

Journal of Chromatographic Science

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The usefulness of thin-layer chromatography (TLC) as an efficient measuring technique in the studies of oscillatory trans-enantiomerization of profens from the S to the R configuration (and vice versa) during their storage as 70% ethanol solutions is demonstrated in the literature. S-(+)-ibuprofen, S-(+)-naproxen, and S,R-(+/-)-2-phenylpropionic acid are utilized as the test profens. It is proven possible to show oscillatory instability with the racemic S,R-(+/-)-2-phenylpropionic acid also. Correctness of the TLC assessment is successfully confirmed by means of polarimetry. Upon these preliminary results, it is concluded that the most probable mechanism might embrace the keto-enol tautomerism because of a convenient migration of the proton from one moiety of the profen molecule to another in an aqueous medium. To indirectly verify this hypothesis, profens are stored in dichloromethane, deliberately hampering their ability to dissociate and to re-structure. It is obvious though that the (much less pronounced) electrolytic dissociation can occur in the non-aqueous media as well. It is shown that the non-aqueous solvent considerably suppresses, although they do not completely eradicate, the oscillatory trans-enantiomerization of profens. In view of these findings, the reports which claim a predominant therapeutic potential of the respective S-profens become less convincing and certainly need reconsideration.

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Stereoselective Disposition of Sustained Release Microspheres of Ibuprofen Enantiomers in Rats: II. Acute Gastrointestinal Toxicity

Cited by 4 publications

References 27 publications

On ups and downs by analysis of profen drugs. A mini review

On ups and downs by analysis of profen drugs. A mini review

Optimization and characterization of novel sustained release supermicro-pellet based dry suspensions that load dexibuprofen

Application of Thin-Layer Chromatography to Investigate Oscillatory Instability of the Selected Profen Enantiomers in Dichloromethane

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