Enantiomeric drug development: Issues, considerations, and regulatory requirements

Srinivas, Nuggehally R.; Barbhaiya, Rashmi H.; Midha, K. K.

doi:10.1002/jps.1074

Cited by 64 publications

(52 citation statements)

References 47 publications

(28 reference statements)

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“…Drug-receptor interactions are highly stereoselective with one enantiomer of a racemic pair providing the desired pharmacological activity, while the other enantiomer may exhibit in the worst case negative side-effects [1,2]. It is therefore essential to separate chiral drugs.…”

Section: Introductionmentioning

confidence: 99%

Capillary zone electrophoretic chiral discrimination using 6‐O‐(2‐hydroxy‐3‐trimethylammoniopropyl)‐β‐cyclodextrin as a chiral selector

Lin

Zhao

Qi³

et al. 2006

Electrophoresis

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A charged highly water-soluble CD derivative, 6-O-(2-hydroxy-3-trimethylammoniopropyl)-beta-CD (herein noted as 6-HPTMA-beta-CD) was synthesized and successfully used as a chiral selector for enantiomeric separation of some acidic compounds by CZE in an uncoated capillary. Substitution with 2-hydroxy-3-trimethylammoniopropyl groups at the primary hydroxyl group of the CD was aimed at influencing the magnitude and selectivity of analyte-CD interactions. The behavior of 6-HPTMA-beta-CD was compared with that of the commercially available quaternary ammonium-beta-CD (QA-beta-CD) under the same separating conditions. The experiments were carried out using a BGE consisting of 50 mM phosphate in the pH range of 4-6 by adding a relatively low concentration of chiral selector (less than 10 mM). The effects of the concentration of CD and the pH of the electrolyte on the resolution of these compounds were studied.

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Section: Introductionmentioning

confidence: 99%

Capillary zone electrophoretic chiral discrimination using 6‐O‐(2‐hydroxy‐3‐trimethylammoniopropyl)‐β‐cyclodextrin as a chiral selector

Lin

Zhao

Qi³

et al. 2006

Electrophoresis

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“…It is generally believed that such study might facilitate the development of highly active, more selective, and less toxic drugs. [2][3][4][5] A survey of different drug areas reveals that asymmetric molecules are relatively common among therapeutics in general. Extensive research has been directed toward isolating and developing stereoisomers that are enantiomers of a variety of experimental and potential candidates ''for development'' compounds.…”

Section: Introductionmentioning

confidence: 99%

Chiral Cardiovascular Drugs

Ranade¹,

Somberg

2005

American Journal of Therapeutics

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Stereochemistry in drug molecules is rapidly becoming an important aspect in drug research, design, and development. Recently, individual stereoisomers of drug molecules with asymmetric centers such as fexofenadine, cetirizine, verapamil, fluoxetine, levalbutarol, and amphetamine, for example, have been separated and developed as individual drugs. These stereoisomers have different therapeutic activity, and each isomer has contributed differently with respect to its formulation's pharmacologic activity, side effects, and toxicity. The present overview discusses chirality among a select group of cardiovascular drugs, their stereochemical synthesis/preparation, isolation techniques using chiral chromatography, methods for confirmation of their enantiomeric purity, pharmacodynamics, and pharmacokinetics. Chirality has been visualized as an important factor in cardiovascular research. It is also becoming evident in other areas of therapeutics.

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“…MIPs are also promising as enantioselective release excipients. A growing awareness of the often profoundly different pharmacokinetic-oral bioavailability, clearance, protein binding, elimination half-life-and also pharmacodynamic and toxicological profiles of the enantiomers of chiral substances has motivated recent regulatory requirements governing their use as pharmaceuticals [29]. Large differences in activity and toxicity justify the necessity of administering pure single enantiomers.…”

Section: Classical Imprinted Particles As Dds Excipientsmentioning

confidence: 99%