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Unread 04-13-2011, 11:57 PM
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Default Supramolecular interactions between losartan and hydroxypropyl-?-CD: ESI mass-spectrometry, NMR techniques, phase solubility, isothermal titration calorimetry and anti-hypertensive studies.

Supramolecular interactions between losartan and hydroxypropyl-?-CD: ESI mass-spectrometry, NMR techniques, phase solubility, isothermal titration calorimetry and anti-hypertensive studies.

Supramolecular interactions between losartan and hydroxypropyl-?-CD: ESI mass-spectrometry, NMR techniques, phase solubility, isothermal titration calorimetry and anti-hypertensive studies.

Int J Pharm. 2011 Feb 14;404(1-2):116-23

Authors: de Paula WX, Denadai AM, Santoro MM, Braga AN, Santos RA, Sinisterra RD

In this work, low soluble supramolecular complex between the losartan potassium (Los) and hydroxypropil-?-cyclodextrin (HP?CD) were characterized throughout phase-solubility, NMR techniques ((1)H and 2D-ROESY) and isothermal titration calorimetry (ITC) in order to attain physical-chemical knowledge of the system. In addition, the hypertensive effect of composition Los/HP?CD was evaluated aiming to obtain a more efficient oral pharmaceutical composition. ESI mass spectrometry and ITC blank experiment demonstrate the presence of Los clusters at 30 mM pure solution. Phase-solubility experiments showed a "Bs" type system, due to the formation of a less soluble complex than pure Los. NMR demonstrated the short distance interactions between the Los and the cyclodextrin, where several possibilities of interactions were observed. ITC data suggest an average 1:1 stoichiometry of Los and the cyclodextrin. The complex demonstrated efficiency in hypertension control, presenting antagonist action on the pressure effect of angiotensin II within 30 h, as compared to Los alone, 6h, indicating that inclusion of Los in HP?CD enhanced the extent and duration of its antagonistic action. In this work, a model of interaction between Los and HP?CD was proposed based on dissociation of self-assembled Los followed by complexation with HP?CD.

PMID: 21093554 [PubMed - indexed for MEDLINE]



Source: PubMed
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