Development of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application

Abstract

NLC topical formulation as an alternative to oral and parenteral (IM) delivery of artemether (ART), a poorly water-soluble drug was designed. A Phospholipon 85G-modified Gelucire 43/01 based NLC formulation containing 75 % Transcutol was chosen from DSC studies and loaded with gradient concentration of ART (100-750 mg). ART-loaded NLCs were stable (-22 to -40 mV), polydispersed (0.4 to 0.7) with d90 size distribution range of 247 to 530 nm without microparticles up to one month of storage. The encapsulation efficiency (EE %) for ART in the NLC was concentration independent as 250 mg of ART loading achieved ~61%. DSC confirmed molecular dispersion of ART due to low matrix crystallinity (0.028 J/g). Ex vivo study showed detectable ART amounts after 20 h which gradually increased over 48 h achieving ~26 % cumulative amount permeated irrespective of the applied dose. This proves that ART permeates excised human epidermis, where the current formulation served as a reservoir to gradually control drug release over an extended period of time. Full thickness skin study therefore may confirm if this is a positive signal to hope for a topical delivery system of ART.

Formulation and Evaluation of Lumefantrine Capsule Prepared by Using Liquisolid Technique

“…Careful passed the level the powder without compacting, and read the unsettled apparent volume (Vo). Calculate the apparent bulk density in gm/ml by the following formula [22].…”

Sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance

“…After oral administration, artemether (ART) is absorbed fairly rapidly with peak plasma concentrations reached in ~2 hours. 3 This invariably implies frequent dosing with associated numerous side effects, especially a nausea-vomiting tendency that makes people discontinue treatment or comply poorly, in addition to many other serious ones. Intramuscularly, absorption is very variable especially in children with poor peripheral perfusion besides the pain of injection.…”

“…4,5 The elimination half-life is ~1 hour and there is no dose modification in renal or hepatic impairment, despite the drug's ability to cause neurotoxicity especially following sustained blood concentration from intramuscular administration. 3 With a novel drug delivery system, such as the nanostructured lipid carrier (NLC), which has been credited as more advantageous over all other colloidal systems (liposomes, nanoemulsions, solid lipid nanoparticles and microemulsions, etc) [6][7][8][9] due to higher drug solubility in liquid lipids (oils) than solid lipids, we aimed to achieve the following: higher encapsulation efficiency (EE), loading capacity, controlled drug release from the payload in the matrix core as well as lower crystallinity of particles. 3,10,11 This will reduce dose-related side effects (ie, improved patient friendliness), facilitate more reproducible absorption than conventional dosage forms as well as protect the drug against degradation in order to achieve site-specific drug delivery.…”

“…NLCs are more advantageous than any other nanoparticle preparation because of their oil-rich core, which makes for greater drug entrapment. 3 More so, fatty food gives 16×…”

Nanocristais de artemeter: preparação e caracterização físico-química

“…A exatidão do método analítico representa o grau de proximidade dos resultados obtidos experimentalmente em relação ao valor verdadeiro (Brasil, 2003 (DONG et al, 2007;NNAMANI et al, 2014). Esses diferem do perfil térmico da matéria-prima artemeter usado no presente trabalho.…”