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Titre du document / Document title

Solubility of (±)-ibuprofen and S (+)-ibuprofen in the presence of cosolvents and cyclodextrins

Auteur(s) / Author(s)

NERURKAR Jayanti (1) ; BEACH J. W. (1) ; PARK M. O. (2) ; JUN H. W. (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) The University of Georgia College of Pharmacy, Athens, Georgia, ETATS-UNIS
(2) Biopolymed, Inc, Seoul, COREE, REPUBLIQUE DE

Résumé / Abstract

Aqueous solubility .is an important parameter for the development of liquid formulations and in the determination of bioavailability of oral dosage forms. Ibuprofen (IB), a nonste-roidal anti-inflammatory drug. is a chiral molecule and is currently used clinically as a racemate (racIB). However, the S form of ibuprofen or S(+)-ibuprofen (SIB) is the biologically active isomer and is primarily responsible for the anti-inflammatory activity. Phase solubility studies were carried out to compare the saturation solubilities of racIB and SIB in the presence of common pharmaceutical solvents such as glycerol, sorbitol solution, propylene glycol (PG), and polyethylene glycol (PEG 300) over the range of 20% to 80% v/v in aqueous based systems. The solubilities of the two compounds were also compared in the presence of cyclodextrins such as beta cyclodextrin (CD), hydroxypropyl beta cyclodextrin (HPCD), and beta cyclodextrin sulfobutyl ether sodium salt (CDSB) over the range of 5% to 25% w/v. Solubility determinations were carried at 25°C and 37°C. Cosolvents exponentially increased the solubility of both SIB and racIB, especially in the presence of PG and PEG 300. Glycerol was not very effective in increasing the aqueous solubilities of both compounds, whereas sorbitol solution had a minimal effect on their solubility. PG and PEG 300 increased the solubility of SIB by 400-fold and 1500-fold, respectively, whereas the rise in solubility for racIB was 193-fold and 700-fold, respectively, at 25°C for the highest concentration of the cosolvents used (80% v/v). Of the two compounds studied, higher equilibrium solubilities were observed for SIB as compared with racIB. The derivatized cyclodextrins increased the aqueous solubility of racIB and SIB in a concentration-dependent manner giving AL type of phase diagrams. The phase solubility diagrams indicated the formation of soluble inclusion complexes between the drugs and HPCD and CDSB, which was of 1:1 stoichiometry. The addition of underivatized CD reduced the solubility of racIB and SIB via the formation of an insoluble complex. The S form formed more stable complexes with HPCD and CDSB as compared with racIB. The solubilization process is discussed in terms of solvent polarity and differential solid-state structure of racIB and SIB. The thermodynamic parameters for the solubilization process are presented.

Revue / Journal Title

Pharmaceutical development and technology    ISSN  1083-7450 

Source / Source

2005, vol. 10, no3, pp. 413-421 [9 page(s) (article)] (23 ref.)

Langue / Language

Anglais

Editeur / Publisher

Informa Healthcare, New York, NY, ETATS-UNIS  (1996) (Revue)

Mots-clés anglais / English Keywords

Enzyme

;

Oxidoreductases

;

Prostaglandin-endoperoxide synthase

;

Enzyme inhibitor

;

Arylpropionic acid derivatives

;

Physicochemical properties

;

Inclusion compound

;

Non steroidal antiinflammatory agent

;

Pharmaceutical technology

;

Complexation

;

Cyclodextrin

;

Cosolvent

;

Ibuprofen

;

Solubility

;

Mots-clés français / French Keywords

Enzyme

;

Oxidoreductases

;

Prostaglandin-endoperoxide synthase

;

Inhibiteur enzyme

;

Arylpropionique acide dérivé

;

Propriété physicochimique

;

Composé inclusion

;

Antiinflammatoire non stéroïde

;

Technologie pharmaceutique

;

Complexation

;

Cyclodextrine

;

Cosolvant

;

Ibuprofène

;

Solubilité

;

Mots-clés espagnols / Spanish Keywords

Enzima

;

Oxidoreductases

;

Prostaglandin-endoperoxide synthase

;

Inhibidor enzima

;

Arilpropionico ácido derivado

;

Propiedad fisicoquímica

;

Compuesto inclusión

;

Antiinflamatorio no esteroide

;

Tecnología farmacéutica

;

Complexación

;

Ciclodextrina

;

Cosolvente

;

Ibuprofeno

;

Solubilidad

;

Mots-clés d'auteur / Author Keywords

ibuprofen

;

solubility

;

cosolvents

;

cyclodextrins

;

inclusion complexation

;

Localisation / Location

INIST-CNRS, Cote INIST : 26544, 35400013173845.0090

Nº notice refdoc (ud4) : 17064993



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