Physicochemical characterization of artemether solid dispersions with hydrophilic carriers by freeze dried and melt methods

Abstract

Solid dispersions of artemether (ARM), a poorly soluble drug, were prepared using polyvinylpyrrolidone (PVPK25, MW 25000) and polyethyleneglycol (PEG4000, MW 4000) as excipients. These dispersions were studied by physical mixture, freeze-drying, and melting methods. They were characterized by X-ray diffraction pattern, fourier transform infrared spectrophotometry, differential scanning calorimetery, and dissolution studies. X-ray diffraction pattern revealed the complete crystalline nature of artemether, whereas physical mixtures, melt mixtures (MM), and freeze-dried solid dispersions (FDSD) of ARM-PVP and ARM-PEG showed reduced peak intensities with increased PVP/PEG content. PEG showed lower decreases in intensity than PVP preparations. Differential scanning calorimetery also confirmed this finding by showing either a small or absent endotherm. Red shifts in O-H stretching vibrations of ARM were higher in the MM of ARM-PVP than its FDSD as exhibited by fourier transform infrared spectrophotometry. The carbonyl peak of PEG was blue shifted in MM and FDSD, whereas the C=O peak of PVP was red shifted in FDSD and MM, indicating different H-bonding by PEG and PVP with ARM. The rate of dissolution (phosphate buffer at pH 4.5) was improved up to 4-fold in MM and FDSD compared to artemether, and up to 50% compared to physical mixtures. The preparation of solid dispersions influenced the rate of dissolution at various drug-carrier ratios, i.e., the dissolution order of 1:1-1:4 ratio was MM > FDSD; FDSD > MM at 1:6-1:8 ratios of both ARM-PVP and ARM-PEG; and FDSD of ARM-PEG > FDSD of ARM-PVP > MM of ARM-PEG > MM of ARM-PVP at a 1:10 ratio.

Pharmaceutical development and optimization of azithromycin suppository for paediatric use

“…These results indicated that one hydrogen bond formed between the free O—H of the AZ and PEG (red shifting) while the second hydrogen bond between a water molecule and AZ was disrupted (blue shifting). These results are consistent with previous data (Ansari et al, 2010) and supported the results of X-ray diffraction.…”

Artemether-Soluplus Hot-Melt Extrudate Solid Dispersion Systems for Solubility and Dissolution Rate Enhancement with Amorphous State Characteristics

“…The literature has shown that higher glass transition temperature and higher viscosity of polymers usually show superior stability for the amorphous drug [9]. The specific interactions between drug and polymer are important considerations for stabilization of the amorphous formulation [10]. Therefore the evaluation and selection of polymer are key factors in developing solid dispersions.…”

Improving the solubility and bioavailability of dihydroartemisinin by solid dispersions and inclusion complexes

“…One of these is polyvinylpyrrolidone (PVP), a vehicle often employed due to its low toxicity, high aqueous solubility and physiological tolerance (Marin et al, 2002;Narang and Srivastava, 2002). Studies on PVPassociated solid dispersions of pharmaceuticals have revealed inhibited crystallization and enhanced solubility; examples include bicalutamide (Andrews et al, 2010), AM (Ansari et al, 2010), piroxicam (Wu et al, 2009), DHA (Ansari and Sunderland, 2008), lamotrigine (Shinde et al, 2008), valdecoxib (Ambike et al, 2004), carbamazepine (Sethia andSquillante, 2004), artemisinin (Nijlen et al, 2003), camptothecin (Kang et al, 2002). Similar studies reported increased bioavailability of ketoconazole (Heo et al, 2005), artemisinin (Wong and Yuen, 2001), norfloxacin (Fawaz et al, 1996), lonidamine (Palmieri et al, 2002) and nifedipine (Emara et al, 2002).…”