Disopyramide Phosphate

Wickman, Alan; Finnegan, Patricia

doi:10.1016/s0099-5428(08)60191-4

Cited by 3 publications

(1 citation statement)

References 19 publications

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“…On the contrary, disopyramide phosphate is also suitable for parenteral administration owing to its high aqueous solubility. The aqueous solubility of free base and disopyramide phosphate is reported as 0.43 and 32 mg/ml (pH 6.0), respectively (Wickman & Finnegan, 1984). The comparative oral pharmacokinetics of disopyramide free base and its phosphate salt demonstrated higher bioavailability of salt over a free base (83% vs. 91%, respectively) (Dubetz et al, 1978; Karim et al, 1982).…”

Section: Pharmaceutical Salts Comprising Phosphate Counterionmentioning

confidence: 99%

Phosphate moiety in FDA‐approved pharmaceutical salts and prodrugs

Fulmali

Bharate

2022

Drug Development Research

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The salification and prodrug approaches modulate the physicochemical properties and absorption, distribution, metabolism, excretion, and toxicity parameters of drugs and lead candidates. The "phosphate" is one of the key counterions/promoiety used in the salt formation and prodrug synthesis. Salification with phosphoric acid enhances the aqueous solubility and thereby facilitates the administration of a drug by the parenteral route. Phosphate moiety in prodrug synthesis mainly improves permeability by lipophilic substitution. Histamine phosphate is the first phosphate salt, and hydrocortisone phosphate was the first prodrug approved by FDA in 1939 and 1952, respectively. The orange book enlists 12 phosphate salts and 17 phosphate prodrugs.Phosphate prodrugs, namely combretastatin A-4 diphosphate, combretastatin A-4 phosphate, lufotrelvir, TP-1287, pyridoxal phosphate, riboflavin phosphate, and psilocybin are clinical candidates. This review focuses on the FDA-approved phosphate salts and prodrugs from 1939 to 2021. The biopharmaceutical advantage of phosphate salts and prodrugs over the parent molecule is also deliberated.

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Section: Pharmaceutical Salts Comprising Phosphate Counterionmentioning

confidence: 99%

Phosphate moiety in FDA‐approved pharmaceutical salts and prodrugs

Fulmali

Bharate

2022

Drug Development Research

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D

Elks¹,

Ganellin²

1990

Dictionary of Drugs

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Crystal Structures of Antiarrhythmic Drug Disopyramide and Its Salt with Phthalic Acid

et al. 2021

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Disopyramide (DPA) is as a class IA antiarrhythmic drug and its crystallization from cyclohexane at ambient condition yields lower melting form crystals which belong to the monoclinic centrosymmetric space group P21/n, having two molecules in an asymmetric unit. Crystal structure analysis of pure DPA revealed closely associated DPA molecules aggregates via amide–amide dimer synthon through the N–H∙∙∙O hydrogen bond whereas the second amide hydrogen N–H engaged in an intramolecular N–H∙∙∙N hydrogen bond with N-nitrogen of 2-pyridine moieties. Crystallization of DPA and phthalic acid (PA) in 1: 1 stoichiometric molar ratio from acetone at ambient condition yielded block shape crystals of 1:1 DPA_PA salt. Its X-ray single crystal structure revealed the formation of salt by transfer of acidic proton from one of the carboxylic acidic groups of PA to the tertiary amino group of chain moiety (N3-nitrogen atom) of DPA molecules. DPA_PA salt crystals belong to the monoclinic centrosymmetric space group P21/n, comprising one protonated DPA and one PA¯ anion (hydrogen phthalate counterion) in an asymmetric unit and linked by N–H∙∙∙O and C–H∙∙∙O hydrogen bonds. Pure DPA and DPA_PA salt were further characterized by differential calorimetric analysis, thermal gravimetric analysis, powder x-ray diffraction and infrared spectroscopy.

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Disopyramide Phosphate

Cited by 3 publications

References 19 publications

Phosphate moiety in FDA‐approved pharmaceutical salts and prodrugs

Phosphate moiety in FDA‐approved pharmaceutical salts and prodrugs

D

Crystal Structures of Antiarrhythmic Drug Disopyramide and Its Salt with Phthalic Acid

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