Artemether

The purpose of the study was to prepare and evaluate liposomes containing Artemether, a lipophilic drug having short half life of 2-3hrs after oral administration. Thin film hydration method was used for the preparation of artemether-encapsulated conventional and PEGylated liposomal suspensions using various drug: lipid ratio and their characteristics, such as particle size, zeta potential, encapsulation efficiency, and in vitro drug release were investigated. The drug encapsulation efficiency of PEGylated liposomes was high when compared to conventional liposomes. The average particle size of both conventional and PEGylated liposomes was obtained in nanometers with PDI ranging from 0-0.356. Zeta potential of conventional liposomes was found to be more negative when compared to PEGylated liposomes. In-vitro drug diffusion studies was carried for period of 16 hrs where PEGylated liposomal formulation showed more sustained release compared to conventional liposomes. The conventional and PEGylated liposomal formulations followed zero order and Higuchi kinetics respectively. The artemether containing liposomes were successfully formulated and evaluated.

Artemether-lumefantrine (ART-LUME) off late has become the first-line treatment for uncomplicated malaria in many Sub-Saharan Africa, Asia and America. Vigorous monitoring of the therapeutic efficacy of this treatment is needed. This requires high-quality studies following standard protocols; ideally, such studies should incorporate measurement of drug levels in human plasma in biological matrices. A specific and reliable isocratic mode RP-HPLC method has been developed and validated for simultaneous determination of artemether (ART) in combination with lumefantrine (LUME) in human plasma using diode array detector (DAD) at 238 nm. The analyte was separated on NUCLEOSIC-CN Cyano coloumn (150 mm × 4.6 mm, particle size 5 μm) using a mobile phase consisting of acetonitrile and acidic buffer (adjusted to pH 2.5 with H3PO4 ­– 2 %) in the ratio of 37: 63 v/v and flow rate was 1 ml/min. The method is linear over a range of 100-1600 µg/ml (r2 ≥ 0.999) and 1-16µg/ml (r2 ≥0.998) for the assay of ART and LUME respectively. Itraconazole (ITZ) (10µg/ml) was used as internal standard. The retention times of ART and LUME was found to be 4.3 min and 14.3 respectively. Mean extraction recovery for ART and LUME were 87.3 % and 89.1 %, respectively. Inter and intraday coefficients of variation for ART and LUME were ≤ 10%. The lower limits of quantification for ART and LUME were 0.22 and 0.66 μg/ml, respectively. The results of the study showed that the proposed RP-HPLC validated method described is efficient and has the necessary accuracy and precision for the rapid quantitative simultaneous determination of ART and LUME in human plasma and is thus highly suitable for use in pharmacokinetic /bioavailability/bioequivalence studies in healthy human subjects.

The objective was to enhance the solubility and dissolution rate of Artemether poorly water soluble antimalarial, by the preparation of solid dispersion (SD) granules. The dispersion granules were prepared using a hot melt granulation technique which involved the preparation of a homogenous dispersion of ARTM in surfactant melt, followed by its adsorption onto the surface of AEROPERL® 300 Pharma, an inert absorbent using the solvent evaporation method. The dispersion granules were characterized for their in-vitro dissolution rate, moisture content and flow properties. The formulation was further characterized by FTIR,DSC, XRD and SEM analysis. FTIR spectrum revealed some drug excipient interactions. DSC and XRD data indicated the retention of amorphous form of ARTM. SEM confirmed the homogeneity and surface adsorption of the ARTM-Lutrol F127 or ARTM-Lutrol F68 melt on AEROPERL® 300 Pharma leading to an enhanced surface area and thus the dissolution rate. The optimized dispersion granules were filled inside the capsules and evaluated. The in-vitro dissolution rate of these capsules was significantly better in comparison with pure drug. Physical characterisation enabled us to understand the effects of formulation variables on the dispersion granules of ARTM.