Solubility determination of raloxifene hydrochloride in ten pure solvents at various temperatures: Thermodynamics-based analysis and solute-solvent interactions

Abdul Ahad; Faiyaz Shakeel; Omar Ali Alfaifi; Mohammad Raish; Ajaz Ahmad; Fahad I Al-Jenoobi; Abdullah M Al-Mohizea

doi:10.1016/j.ijpharm.2018.04.024

Solubility determination of raloxifene hydrochloride in ten pure solvents at various temperatures: Thermodynamics-based analysis and solute-solvent interactions

Int J Pharm. 2018 Jun 10;544(1):165-171. doi: 10.1016/j.ijpharm.2018.04.024. Epub 2018 Apr 18.

Authors

Abdul Ahad¹, Faiyaz Shakeel², Omar Ali Alfaifi², Mohammad Raish², Ajaz Ahmad³, Fahad I Al-Jenoobi², Abdullah M Al-Mohizea²

Affiliations

¹ Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: abdulahad20@yahoo.com.
² Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
³ Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

PMID: 29679751
DOI: 10.1016/j.ijpharm.2018.04.024

Abstract

The purpose of the present study was to determine the solubility of raloxifene hydrochloride (RHCl) in ten solvents: water, ethanol, isopropyl alcohol (IPA), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), Transcutol, 1-butanol, dimethyl sulfoxide (DMSO), and ethyl acetate (EA) at temperatures of 298.2-323.2 K and a pressure of 0.1 MPa. The solubility data obtained was fitted upon "Apelblat and Van't Hoff" equations. The maximum mole fraction solubility of RHCl was obtained in DMSO (5.02 × 10^-2 at 323.2 K), followed by PEG-400 (5.92 × 10^-3 at 323.2 K), EA (3.11 × 10^-3 at 323.2 K), Transcutol (1.22 × 10^-3 at 323.2 K), PG (2.19 × 10^-4 at 323.2 K), 1-butanol (1.96 × 10^-4 at 323.2 K), IPA (1.47 × 10^-4 at 323.2 K), ethanol (7.90 × 10^-5 at 323.2 K), EG (6.65 × 10^-5 at 323.2 K), and water (3.60 × 10^-5 at 323.2 K). Similar fashions were noticed at each studied temperature. The higher solubility of RHCl in DMSO, PEG-400, EA, and Transcutol was possibly referable to their lower polarity in comparison with water. The molecular interactions between the solute and solvent molecules were estimated by calculating parameters like activity coefficients, and more prominent solute-solvent molecular interactions were noted for RHCl-DMSO, RHCl-EA, and RHCl-PEG-400 in comparison with the other solute-solvent combinations. The outcomes of the "apparent thermodynamic analysis" showed that the dissolution of RHCl was "endothermic, spontaneous and entropy-driven" in all investigated solvents. The obtained solubility data of RHCl in commonly used solvents could be useful in the purification, recrystallization, and dosage form design of the drug.

Keywords: 1-Butanol (PubChem CID: 263); Acetonitrile (PubChem CID: 6342); Apelblat equation; Dimethyl sulfoxide (PubChem CID: 679); Dissolution; Ethanol (PubChem CID: 702); Ethyl acetate (PubChem CID: 8857); Ethylene glycol (PubChem CID: 174); Isopropyl alcohol (PubChem CID: 3776); Polyethylene glycol-400 (PubChem CID: 174); Propylene glycol (PubChem CID: 1030); Raloxifene hydrochloride; Raloxifene hydrochloride (PubChem CID: 54900); Solubility; Thermodynamics; Transcutol (PubChem CID: 8146).

MeSH terms

Estrogen Antagonists / chemistry*
Powder Diffraction
Raloxifene Hydrochloride / chemistry*
Solubility
Solvents / chemistry*
Temperature
Thermodynamics
X-Ray Diffraction

Substances

Estrogen Antagonists
Solvents
Raloxifene Hydrochloride