Repaglinide, a new oral antidiabetic agent: a review of recent preclinical studies

Malaisse, Willy

doi:10.1046/j.1365-2362.1999.00001.x

Cited by 25 publications

(10 citation statements)

References 20 publications

(48 reference statements)

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“…Repaglinide exerts its effects by binding to a site on plasma membrane of beta cells, thereby closing ATP-sensitive potassium channels. 4 Repaglinide, a novel compound with a nonsulphonylurea structure, was clinically tested as a therapeutic agent. The hypoglycemic effects of repaglinide were investigated.…”

Section: Repaglinide (Figure 1) Single Enantiomer Is Chemically (S)-(mentioning

confidence: 99%

A validated chiral LC method for the enantiomeric separation of repaglinide on immobilized amylose based stationary phase

Patil¹,

Rane²,

Yeole³

et al. 2012

J. Braz. Chem. Soc.

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Um método de HPLC quiral em fase normal, simples, rápido, isocrático, foi desenvolvido e validado para a separação enantiomérica de repaglinida, ácido (S)-(+)-2-etóxi-4-N [1-(2-piperidinofenil)-3-metil-1-butil] aminocarbonilmetil] benzóico, uma substância antidiabética. Os enantiômeros de repaglinida foram resolvidos em uma coluna Chiralpak IA (fase estacionária a base de amilose imobilisada) usando uma fase móvel consistindo de n-hexano:etanol:ácido trifluoroacético (80:20:20, v/v/v) a uma vazão de 1,0 mL min -1 . A resolução encontrada entre os enantiômeros foi maior do que 2 no método otimizado. O método desenvolvido foi extensivamente validado e mostrou-se robusto, enantiosseletivo, exato, preciso e adequado para determinação quantitativa de (R)-enantiômero na substância a granel e no produto formulado.A simple, rapid, isocratic, normal phase chiral HPLC method was developed and validated for the enantiomeric separation of repaglinide, (S)-(+)-2-ethoxy-4-N [1-(2-piperidinophenyl)-3-methyl-1-butyl] aminocarbonylmethyl] benzoic acid, an antidiabetic drug substance. The enantiomers of repaglinide were resolved on a Chiralpak IA (immobilized amylose based stationary phase) column using a mobile phase consisting of n-hexane:ethanol:trifluoroacetic acid (80:20:0.2, v/v/v) at a flow rate of 1.0 mL min -1 . The resolution between both enantiomers was greater than 2 in the optimized method. The developed method was extensively validated and proved to be robust, enantioselective, accurate, precise, and suitable for quantitative determination of (R)-enantiomer in bulk drug substance and product.

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Section: Repaglinide (Figure 1) Single Enantiomer Is Chemically (S)-(mentioning

confidence: 99%

A validated chiral LC method for the enantiomeric separation of repaglinide on immobilized amylose based stationary phase

Patil¹,

Rane²,

Yeole³

et al. 2012

J. Braz. Chem. Soc.

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“…It achieves this by closing ATP-dependent potassium channels in the membrane of the beta cells. [5,6] Repaglinide is well tolerated in general and also in elderly diabetic patients and people with diabetes and mild or moderate renal or hepatic impairment. [7] Fixed dose (0.5 mg) clinical trial are supportive of the efficacy and safety of Repaglinide to produce significant improvement in glycemic control.…”

Section: Introductionmentioning

confidence: 99%

Identification, isolation, and synthesis of seven novel impurities of anti‐diabetic drug Repaglinide

Prasad

Srinivas²,

Alegete

et al. 2017

Drug Testing and Analysis

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Seven unknown impurities in Repaglinide bulk drug batches at below 0.1% (ranging from 0.05 to 0.10%) were detected by an ultra-performance liquid chromatographic (UPLC) method. These impurities were isolated from the crude sample of Repaglinide using preparative high performance liquid chromatography (prep-HPLC). Based on liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI/MS) study, the chemical structures of seven new impurities (8, 9, 10, 11, 13, 14, and 16) were presumed and characterized as 4-(cyanomethyl)-2-ethoxybenzoic acid (8), 4-(cyanomethyl)-2-ethoxy-N-(3-methyl-1-(2-(piperidin-1-yl)phenyl)butyl)benzamide (9), 4-(2-amino-2-oxoethyl)-2-ethoxy-N-(3-methyl-1-(2-(piperidin-1-yl)phenyl)butyl) benzamide (10) and 2-(3-ethoxy-4-((3-methyl-1-(2-(piperidin-1-yl)phenyl)butyl) carbamoyl) phenyl) acetic acid (11) and 4-(cyanomethyl)-Ncyclohexyl-2-ethoxybenzamide (13), 2-(4-(cyclohexylcarbamoyl)-3-ethoxyphenyl) acetic acid (14) and N-cyclohexyl-4-(2-(cyclohexylamino)-2-oxoethyl)-2-ethoxybenzamide (16). The complete spectral analysis, proton nuclear magnetic resonance ( 1 H NMR), 13 C NMR, MS, and infrared (IR) confirmed the proposed chemical structures of impurities. Identification, structural characterization, formation, and their synthesis was first reported in this study. The impurity 11 was crystallized and structure was solved by single crystal X-ray diffraction.

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“…It stimulates the release of insulin by binding to a receptor that is distinct from sulfonylurea receptor (2,3). RPG is practically insoluble in water with a solubility of 34 μg/mL (4).…”

Section: Introductionmentioning

confidence: 99%

Design and Evaluation of Self-Nanoemulsifying Pellets of Repaglinide

Desai

Nagarsenker

2013

AAPS PharmSciTech

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Abstract. The aim of study was to develop self-nanoemulsifying pellets (SNEP) for oral delivery of poorly water soluble drug, repaglinide (RPG). Solubility of RPG in oily phases and surfactants was determined to identify components of self-nanoemulsifying drug delivery system (SNEDDS). The surfactants and cosurfactants were screened for their ability to emulsify oily phase. Ternary phase diagrams were constructed to identify nanoemulsification area for the selected systems. SNEDDS formulations with globule size less than 100 nm were evaluated for in vivo anti-hyperglycemic activity in neonatal streptozotocin rat model. A significant reduction in glucose levels was produced by optimized SNEDDS formulation in comparison to the control group. The optimized SNEDDS formulations were pelletized via extrusion/spheronization technique using microcrystalline cellulose and lactose. SNEP were characterized by X-ray powder diffraction and scanning electron microscopy. X-ray diffraction study indicated loss of crystallinity of RPG in SNEP. The SNEP exhibited good flow properties, mechanical strength and formed nanoemulsion with globule size less than 200 nm. SNEP showed in vitro release of more than 80% RPG in 10 min which was significantly higher than RPG containing reference pellets. In conclusion, our studies illustrated that RPG, a poorly water soluble drug can be successfully formulated into SNEP which can serve as a promising system for the delivery of poorly water soluble drugs.

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Repaglinide, a new oral antidiabetic agent: a review of recent preclinical studies

Cited by 25 publications

References 20 publications

A validated chiral LC method for the enantiomeric separation of repaglinide on immobilized amylose based stationary phase

A validated chiral LC method for the enantiomeric separation of repaglinide on immobilized amylose based stationary phase

Identification, isolation, and synthesis of seven novel impurities of anti‐diabetic drug Repaglinide

Design and Evaluation of Self-Nanoemulsifying Pellets of Repaglinide

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