Improved physicochemical characteristics of artemisinin using succinic acid.

Abstract

Artemisinin (ARMN) is a potent antimalarial drug, which is effective against multidrug resistant strains of Plasmodium falciparum and produces rapid recovery even in patients with cerebral malaria. Being poorly soluble in water, artemisinin is incompletely absorbed after oral intake due to poor dissolution characteristics in the intestinal fluids. To enhance these properties, solid dispersions of artemisinin with succinic acid (SUC) were prepared using drug-carrier ratios 1 : 1, 1 : 4, 1 : 6, 1 : 8 and 1 : 10 by solvent evaporation and freeze drying methods. These solid dispersions were characterized by differential scanning calorimetery (DSC), Fourier transform infrared spectroscopy (FTIR), x-ray diffraction patterns (XRD), phase solubility and dissolution kinetics evaluated by applying zero order, first order, Higuchi, and Korsmeyer-Peppas models. Physical mixtures produced significantly higher aqueous solubility and rate of dissolution as compared to artemisinin alone. The dissolution profiles of all formulations followed Higuchi model and exhibited diffusion-controlled release of drug. Solvent evaporation method (SLVPs) exhibited improved solubility and freeze dried solid dispersions (FDSDs) produced highest solubility but stability constant was opposite. ARMN and SUC both were found completely crystalline as shown by their XRD patterns. Physical mixtures (PMs) showed reduced intensity in their XRD patterns while solid dispersions by SLVPs exhibited twice reduced intensity and much displaced angles, whereas FDSDs showed synergistic effects in some of ARMN and SUC peaks. DSC thermograms of FDSDs at drug-carrier ratios 1 : 1-1 : 4 showed lower melting temperature and enthalpy change (deltaH) values than respective SLVPs, whereas at higher ratios, a reverse was true. SLVPs showed displaced methyl stretching bands at lower drug-carrier ratios and exhibited O-H stretching characteristic bands of SUC at higher drug-carrier ratios. In addition, carbonyl group and C-O stretching vibrations characteristic of SUC (1307 cm(-1)) appeared prominently compared to PMs, whereas C-O stretching characteristic bands of ARMN disappeared at higher ratios. FDSDs exhibited distinct nature of bonding compared to respective SLVPs and PMs.

• Authors: Muhammad Tayyab Ansari, Humayun Pervez, Muhammad Tariq Shehzad, Syed Saeed-ul-Hassan, Zahid Mehmood, Syed Nisar Hussain Shah, Muhammad Tahir Razi, Ghulam Murtaza
• Journal: Acta poloniae pharmaceutica (Acta Pol Pharm) 2014 May-Jun Vol. 71 Issue 3 Pg. 451-62 ISSN: 0001-6837 [Print] Poland
• PMID: 25265825 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Artemisinins
• Excipients
• Solvents
• artemisinin
• Succinic Acid

Topics

• Antimalarials (chemistry)
• Artemisinins (chemistry)
• Calorimetry, Differential Scanning
• Chemistry, Pharmaceutical
• Crystallography, X-Ray
• Diffusion
• Excipients (chemistry)
• Freeze Drying
• Kinetics
• Models, Chemical
• Solubility
• Solvents (chemistry)
• Spectroscopy, Fourier Transform Infrared
• Succinic Acid (chemistry)
• Technology, Pharmaceutical (methods)
• Transition Temperature