title: Preparation and Characterization of Solid Dispersions of Artemether by Freeze-Dried Method.
abstract: Solid dispersions of artemether and polyethylene glycol 6000 (PEG6000) were prepared in ratio 12 : 88 (group-1). Self-emulsified solid dispersions of artemether were prepared by using polyethylene glycol 6000, Cremophor-A25, olive oil, Transcutol, and hydroxypropyl methylcellulose (HPMC) in ratio 12 : 75 : 5 : 4 : 2 : 2, respectively (group-2). In third group, only Cremophor-A25 was replaced with Poloxamer 188 compared to group-2. The solid dispersions and self-emulsified solid dispersions were prepared by physical and freeze dried methods, respectively. All samples were characterized by X-ray diffraction, attenuated total reflectance Fourier transform infrared spectroscopy, differential scanning calorimeter, scanning electron microscopy, and solubility, dissolution, and stability studies. X-ray diffraction pattern revealed artemether complete crystalline, whereas physical mixture and freeze-dried mixture of all three groups showed reduced peak intensities. In attenuated total reflectance Fourier transform infrared spectroscopy spectra, C-H stretching vibrations of artemether were masked in all prepared samples, while C-H stretching vibrations were representative of polyethylene glycol 6000, Cremophor-A25, and Poloxamer 188. Differential scanning calorimetry showed decreased melting endotherm and increased enthalpy change (ΔH) in both physical mixture and freeze-dried mixtures of all groups. Scanning electron microscopy of freeze-dried mixtures of all samples showed glassy appearance, size reduction, and embedment, while their physical mixture showed size reduction and embedment of artemether by excipients. In group-1, solubility was improved up to 15 times, whereas group-2 showed up to 121 times increase but, in group-3, when Poloxamer 188 was used instead of Cremophor-A25, solubility of freeze-dried mixtures was increased up to 135 times. In fasted state simulated gastric fluid at pH 1.6, the dissolution of physical mixture was increased up to 12 times and freeze-dried mixtures up to 15 times. The stability of artemether was substantially enhanced in freeze-dried mixtures by using polyethylene glycol 6000, Cremophor-A25, and Poloxamer 188 of self-emulsified solid dispersions of artemether in Hank's balanced salt solution at pH 7.4.
authors.affiliation: Faculty of Pharmacy, Bahauddin Zakariya University, Multan 6000, Pakistan.
authors.forename: Muhammad Tayyab
authors.initials: MT
authors.lastname: Ansari
authors.affiliation: Faculty of Pharmacy, Bahauddin Zakariya University, Multan 6000, Pakistan.
authors.forename: Altaf
authors.initials: A
authors.lastname: Hussain
authors.affiliation: Faculty of Pharmacy, Bahauddin Zakariya University, Multan 6000, Pakistan.
authors.forename: Sumaira
authors.initials: S
authors.lastname: Nadeem
authors.affiliation: Faculty of Pharmacy, Bahauddin Zakariya University, Multan 6000, Pakistan.
authors.forename: Humaira
authors.initials: H
authors.lastname: Majeed
authors.affiliation: College of Pharmacy, University of the Punjab, Lahore 54000, Pakistan.
authors.forename: Syed
authors.initials: S
authors.lastname: Saeed-Ul-Hassan
authors.affiliation: College of Pharmacy, University of the Punjab, Lahore 54000, Pakistan.
authors.forename: Imran
authors.initials: I
authors.lastname: Tariq
authors.affiliation: Department of Environmental Sciences, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Qaisar
authors.initials: Q
authors.lastname: Mahmood
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Abida Kalsoom
authors.initials: AK
authors.lastname: Khan
authors.affiliation: Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Ghulam
authors.identifier: 0000-0001-5649-5768
authors.initials: G
authors.lastname: Murtaza
mesh_terms: D000077549:Artemether; D037621:Artemisinins / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions / Q000737:chemistry; D005612:Freeze Drying; D065347:Hypromellose Derivatives / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D037621:Artemisinins; D004337:Drug Carriers; D004655:Emulsions; D020442:Poloxamer; C022131:cremophor; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D000077549:Artemether