Abstract
Estimating the solubility and solution thermodynamics parameters of aliskiren hemifumarate (AHF) in three different room temperature ionic liquids (RTILs), Transcutol-HP (THP) and water are interesting as there is no solubility data available in the literature. In the current study, the solubility and solution thermodynamics of AHF in three different RTILs, THP and water at the temperature range from 298.2 to 318.2 K under air pressure 0.1 MP were evaluated. The solid phase evaluation by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD) indicated no conversion of AHF into polymorph. The mole fraction solubility of AHF was found to be highest in 1-hexyl-3-methylimidazolium hexafluorophosphate (HMMHFP) ionic liquid (7.46 × 10−2) at 318.2 K. The obtained solubility values of AHF was regressed by the Apelblat and van’t Hoff models with overall root mean square deviations (RMSD) of 0.62% and 1.42%, respectively. The ideal solubility of AHF was higher compared to experimental solubility values at different temperatures. The lowest activity coefficient was found in HMMHFP, which confirmed highest molecular interaction between AHF–HMMHFP. The estimated thermodynamic parameters confirmed endothermic and entropy driven dissolution of AHF in different RTILs, THP, and water.
Highlights
Renin is an enzyme secreted by the kidney and plays a key role in the pathogenesis of arterial hypertension and its consequent complication associated with cardiovascular and renal diseases [1]
Solid phase characterization of theX-ray initialDiffraction and equilibrated sampleanalysis were performed by Scanning Calorimetry (DSC) and Powder (PXRD) spectral to know about spectral analysis to the crystallinity/amorphicity and various thermal parameters of the drug
aliskiren hemifumarate (AHF), BMMHFP, hexyl-3-methylimidazolium hexafluorophosphate (HMMHFP), and OMMHFP were purchased from Mesochem Technology (Beijing, China)
Summary
Renin is an enzyme secreted by the kidney and plays a key role in the pathogenesis of arterial hypertension and its consequent complication associated with cardiovascular and renal diseases [1]. Aliskiren hemifumarate (AHF) is the first clinically approved, orally active, highly potent, and selective renin inhibitor for the treatment of hypertension alone or in combination with other antihypertensive agents [2]. It is chemically designated as (2S,4S,5S,7S)-N-(2-Carbamoyl-2methylpropyl)-5amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxypropoxy)phenyl]octanamidehemifumarate (Figure 1). In spite of high potency, aliskiren is poorly absorbed (2.5% oral bioavailability) and reflects a high inter-subject variability in their pharmacokinetic profile after oral. Molecules 2019, 24, x FOR PEER REVIEW. Molecules 2019, 24, 2807 bioavailability) and reflects a high inter-subject variability in their pharmacokinetic profile after oral administration [3,4].
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call