1.Systemic Delivery of Artemether by Dissolving Microneedles.
Qiu Y1, Li C1, Zhang S1, Yang G1, He M1, Gao Y2. Int J Pharm. 2016 May 2. pii: S0378-5173(16)30372-6. doi: 10.1016/j.ijpharm.2016.05.006. [Epub ahead of print]
Dissolving microneedles (DMNs) based transdermal delivery is an attractive drug delivery approach with minimal invasion. However, it is still challenging to load poorly water-soluble drugs in DMNs for systemic delivery. The aim of the study was to develop DMNs loaded with artemether (ARM) as a model drug, to enable efficient drug penetration through skin for systemic absorption and distribution. The micro-conduits created by microneedles were imaged by confocal laser scanning microscopy (CLSM), and the insertion depth was suggested to be about 270μm. The maximum amount of ARM delivered into skin was 72.67±2.69% of the initial dose loaded on DMNs preparation. Pharmacokinetics study in rats indicated a dose-dependent profile of plasma ARM concentrations, after ARM-loaded DMNs treatment. In contrast to intramuscular injection, DMNs application resulted in lower peak plasma levels, but higher plasma ARM concentration at 8hours after administration.
2.Systematic development of optimized SNEDDS of artemether with improved biopharmaceutical and antimalarial potential.
Tripathi CB1, Beg S1, Kaur R2, Shukla G3, Bandopadhyay S4, Singh B1,2. Drug Deliv. 2016 Mar 29:1-15. [Epub ahead of print]
The current studies entail systematic development of self-nanoemulsifying drug delivery systems (SNEDDS) containing medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs) for augmenting the biopharmaceutical performance of artemether. Equilibrium solubility and pseudoternary phase diagram studies facilitated selection of Captex 355 and Ethyl oleate as MCTs and LCTs, and Cremophor RH 40 and Tween 80 as surfactants, while Transcutol HP as cosolvent for formulating the SNEDDS. Systematic optimization was performed employing the Box-Behnken design taking concentrations of lipid, surfactant and cosolvent as the critical material attributes (CMAs), while evaluating for globule size, emulsification time, dissolution efficiency and permeation as the critical quality attributes (CQAs). In situ single pass intestinal perfusion (SPIP) studies in Wistar rats substantiated significant augmentation in the absorption (5- to 6-fold) and permeation (4- to 5-fold) parameters from the optimized MCT and LCT-SNEDDS vis-à-vis the pure drug.
3.Apoptotic activity and anti-Toxoplasma effects of artemether on the tachyzoites and experimental infected Vero and J774 cell lines by Toxoplasma gondii.
Mikaeiloo H1, Ghaffarifar F1, Dalimi A1, Sharifi Z2, Hassan ZM3. Indian J Pharmacol. 2016 Mar-Apr;48(2):179-85. doi: 10.4103/0253-7613.178838.
OBJECTIVES: Drugs used for toxoplasmosis have limited efficacy and also severe side effects. A new drug with good efficacy and limited side effects is need of the hour. We studied the effects of artemether on Toxoplasma gondii in vitro conditions.
4.Artemether-Lumefantrine Concentrations in Tablets and Powders from Ghana Measured by a New High-Performance Liquid Chromatography Method.
Debrah P1, Nettey H2, Miltersen KK2, Ayeh-Kumi P2, Brock B2, Sarkodie J2, Akwo-Kretchy I2, Owusu-Danso P2, Adjei S2, Petersen E2, Hardlei TF2. Am J Trop Med Hyg. 2016 May 2. pii: 15-0868. [Epub ahead of print]
We developed and validated a new analytical method for the simultaneous quantification of artemether and lumefantrine in fixed-dose tablets and powders for reconstitution into pediatric suspensions (PSs). The method showed linearity (r2 > 0.9947), precision (coefficient of variation < 2%), accuracy (deviation of mean from actual concentrations < 4%), and specificity (peak purities > 99%). The validated method was used to analyze 24 batches of fixed-dose tablets and PSs of artemether and lumefantrine. Of the samples, 23 were obtained using convenience sampling of commonly available brands within Accra in Ghana and one was obtained from Aarhus University Hospital. In all, 83.3% (confidence interval: 80-120%) passed for both artemether and lumefantrine contents, 16.7% failed by the U.S. Pharmacopoeia standards, 8.3% failed for one content, and 8.3% failed for both contents. All four products (16.7%) that failed were PSs, and two (8.