Physicochemical characterization of artemether solid dispersions with hydrophilic carriers by freeze dried and melt methods.
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.
Ansari
Muhammad Tayyab
MT
Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan. Ansari.Muhammad@gmail.com
Karim
Shahid
S
Ranjha
Nazar Muhammad
NM
Shah
Nisar Hussain
NH
Muhammad
Sher
S
D000962:Antimalarials / Q000008:administration & dosage* / Q000032:analysis; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage* / Q000032:analysis; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D018360:Crystallography, X-Ray; D004337:Drug Carriers / Q000008:administration & dosage* / Q000032:analysis; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying; D005615:Freezing; D057927:Hydrophobic and Hydrophilic Interactions; D011092:Polyethylene Glycols / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012556:Schistosomicides / Q000008:administration & dosage* / Q000032:analysis; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013535:Suspensions; D013997:Time Factors
D000962:Antimalarials; D037621:Artemisinins; D004337:Drug Carriers; D005079:Excipients; D012556:Schistosomicides; D013535:Suspensions; D011092:Polyethylene Glycols; D000077549:Artemether; D011205:Povidone