Solid microemulsion preconcentrate (NanOsorb) of artemether for effective treatment of malaria.
A microemulsion preconcentrate was formulated on the basis of solubility of artemether (ARM) in the various oily phases and surfactants and phase diagrams. Various solid adsorbents were evaluated for their ability yield solid microemulsion preconcentrates (NanOsorb-ARM). NanOsorb-ARM on dilution yielded microemulsion with average globule size of 183 nm and polydispersity index of 0.498 when determined using photon correlation spectroscopy. The antimalarial activity of NanOsorb-ARM, ARM solution and marketed ARM formulation (Larither) was evaluated in Plasmodium berghei infected mice as per Peter's four day protocol. The acute lethal dose and the subacute toxicity of NanOsorb-ARM were determined as per the method suggested in Organization for Economic Cooperation and Development (OECD) guidelines. The NanOsorb-ARM exhibited significantly higher antimalarial activity (P<0.05) as compared to the marketed formulation of artemether (Larither). Surprisingly, placebo NanOsorb also showed significantly higher antimalarial activity as compared to Larither indicating that excipients used for the formulation of NanOsorb may have antimalarial activity. Subacute toxicity studies demonstrated that NanOsorb-ARM is comparatively safer than artemether oily solution with respect to survival, gross pathology, hematology and serum biochemistry in mice of both the genders.
Joshi
Medha
M
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology (Autonomus), N. P. Marg, Matunga, Mumbai 400019, India.
Pathak
Sulabha
S
Sharma
Shobhona
S
Patravale
Vandana
V
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D004339:Drug Compounding; D004655:Emulsions; D007928:Lethal Dose 50; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D051379:Mice; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D010962:Plasmodium berghei / Q000187:drug effects / Q000254:growth & development; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D018675:Toxicity Tests
D000962:Antimalarials; D037621:Artemisinins; D004337:Drug Carriers; D004655:Emulsions; D009821:Oils; D013501:Surface-Active Agents; D000077549:Artemether