Development and Validation of a Dissolution Test Method for Artemether and Lumefantrine in Tablets

Umapathi, P.; Ayyappan, J; Quine, S. Darlin

doi:10.4314/tjpr.v10i5.14

Cited by 13 publications

(16 citation statements)

References 6 publications

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“…Accroding to noyes-whitney equation reduction in droplet size lead to significant enhancement in dissolution while Prandlt equation suggests the significant reduction in diffusion layer thickness with nanosizing of particle [16]. …”

Section: Discussionmentioning

confidence: 99%

“…USP recommonds use of 1% w/v Benzalkonium chloride (BKC) in dissoultion media. The saturation solubilty of LF in 0.1 M HCl with 1% w/v BKC is 119 ± 3 ppm, sufficient to solubilize 120 mg of LF in dissolution media [16]. The most important advantage of LF-SNEDs system is complete dissolution of LF without use of such surfactant in dissoltion media.…”

Section: Discussionmentioning

confidence: 99%

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Design and evaluation of Lumefantrine – Oleic acid self nanoemulsifying ionic complex for enhanced dissolution

2013

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BackgroundLumefantrine, an antimalarial molecule has very low and variable bioavailability owing to its extremely poor solubility in water. It is recommended to be taken with milk to enhance its solubility and bioavailability. The aim of present study was to develop a Self Nanoemulsifying Delivery system (SNEDs) of lumefantrine (LF) to achieve rapid and complete dissolution independent of food-fat and surfactant in dissolution media.MethodsSolubility of LF in oil, co-solvent/co-surfactant and surfactant solution and emulsification efficiency of surfactant were analyzed to optimize the LF loaded self nanoemulsifying preconcentrate. Effect of LF-oleic acid complexation on emulsification, droplet size, zeta potential and dissolution were investigated. Effect of milk concentration and fat content on saturation solubility and dissolution of LF was investigated. Dissolution of marketed formulation and LF-SNEDs was carried out in pH 1.2 and pH 6.8 phosphate buffer.ResultsLF exhibited very high solubility in oleic acid owing to complexation between tertiary amine of LF and carboxyl group of oleic acid (OA). Cremophore EL and medium chain monoglyceride were selected surfactant and co-surfactant, respectively. Significantly smaller droplet size (37 nm), shift in zeta potential from negative to positive value, very high drug loading in lipid based system (> 10%), no precipitation after dissolution are the major distinguish characteristics contributed by LF-OA complex in the SNED system. Saturation solubility and dissolution study in milk containing media pointed the significant increment in solubility of LF in the presence of milk-food fat. LF-SNEDs showed > 90% LF release within 30 min in pH 1.2 while marketed tablet showed almost 0% drug release.ConclusionSelf nanoemulsification promoting ionic complexation between basic drug and oleic acid hold great promise in enhancing solubility of hydrophobic drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Design and evaluation of Lumefantrine – Oleic acid self nanoemulsifying ionic complex for enhanced dissolution

2013

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“…Dissolution tests were performed using the USP apparatus II (paddle method) at 100 rpm, which has been reported by Umapathi et al21 The dissolution medium (1,000 mL) chosen for dissolution testing was composed of phosphate buffer at pH 7.2 and 1% sodium dodecyl sulfate, which has previously been reported by Pawar et al50…”

Section: Methodsmentioning

confidence: 99%

“…The therapeutic response of this important active pharmaceutical ingredient (API), however, has been reported to be adversely affected by its erratic oral bioavailability due to its poor water solubility 18. Although this compound is a potent and lipid-soluble derivative of artemisinin,19,20 its poor water solubility (133±4 µg/mL) and low bioavailability (<40%) are considered to be major barriers to the development of a commercial dosage form 21…”

Section: Introductionmentioning

confidence: 99%

Smart nanocrystals of artemether: fabrication, characterization, and comparative in vitro and in vivo antimalarial evaluation

Shah¹,

Ullah²,

Khan³

et al. 2016

DDDT

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Artemether (ARTM) is a very effective antimalarial drug with poor solubility and consequently low bioavailability. Smart nanocrystals of ARTM with particle size of 161±1.5 nm and polydispersity index of 0.172±0.01 were produced in <1 hour using a wet milling technology, Dena® DM-100. The crystallinity of the processed ARTM was confirmed using differential scanning calorimetry and powder X-ray diffraction. The saturation solubility of the ARTM nanocrystals was substantially increased to 900 µg/mL compared to the raw ARTM in water (145.0±2.3 µg/mL) and stabilizer solution (300.0±2.0 µg/mL). The physical stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C–8°C and 25°C were very stable compared to the samples stored at 40°C. The nanocrystals were also shown to be stable when processed at acidic pH (2.0). The solubility and dissolution rate of ARTM nanocrystals were significantly increased (P<0.05) compared to those of its bulk powder form. The results of in vitro studies showed significant antimalarial effect (P<0.05) against Plasmodium falciparum and Plasmodium vivax. The IC50 (median lethal oral dose) value of ARTM nanocrystals was 28- and 54-fold lower than the IC50 value of unprocessed drug and 13- and 21-fold lower than the IC50 value of the marketed tablets, respectively. In addition, ARTM nanocrystals at the same dose (2 mg/kg) showed significantly (P<0.05) higher reduction in percent parasitemia (89%) against P. vivax compared to the unprocessed (27%), marketed tablets (45%), and microsuspension (60%). The acute toxicity study demonstrated that the LD50 value of ARTM nanocrystals is between 1,500 mg/kg and 2,000 mg/kg when given orally. This study demonstrated that the wet milling technology (Dena® DM-100) can produce smart nanocrystals of ARTM with enhanced antimalarial activities.

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“…The British Pharmacopoeia (BP) , and the United States Pharmacopeia (USP) recommend non‐aqueous titration and HPLC for the assay of MET in raw material and tablets, respectively. Most reported chromatographic methods are for the assay of MET in formulations and plasma . HPLC–MS has been employed for determination of MET in plasma and the environment .…”

Section: Introductionmentioning

confidence: 99%

Simultaneous analysis of metformin and cyanoguanidine by capillary zone electrophoresis and its application in a stability study

Doomkaew

Prutthiwanasan

Suntornsuk

2014

J of Separation Science

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A capillary zone electrophoresis method was established for stability study of metformin (MET). MET and cyanoguanidine (CGN; a major degradation product) were well separated (with a resolution of 38.9) in 40 mM citrate buffer (pH 6.7) using a fused-silica capillary with an effective length of 60 cm and an inner diameter of 50 μm, injection at 50 mbar for 5 s at 30°C with an applied voltage of 15 kV and diode array detection at 214 nm. Method validation showed good linearity (r(2) > 0.99), precision (%RSDs < 1.98%), and accuracy (%recovery between 98.3 and 100.9%). Limits of detection and quantification were <30 and 100 μg/mL, respectively. The method was robust upon alteration of pH and voltage (%RSDs < 1.99%). Stability profiles of metformin from 11 stress conditions and the degradation kinetics could be established, using the simple capillary zone electrophoresis system. A mechanism for the degradation of MET was also proposed. MET was stable in neutral hydrolysis, but degraded under alkaline hydrolysis and oxidation. Under both conditions, CGN was quantified as the degradation product. An assay of MET in raw material and tablets showed that content of the drugs in all samples met the requirements of pharmacopeias and CGN was not detected.

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Development and Validation of a Dissolution Test Method for Artemether and Lumefantrine in Tablets

Cited by 13 publications

References 6 publications

Design and evaluation of Lumefantrine – Oleic acid self nanoemulsifying ionic complex for enhanced dissolution

Design and evaluation of Lumefantrine – Oleic acid self nanoemulsifying ionic complex for enhanced dissolution

Smart nanocrystals of artemether: fabrication, characterization, and comparative in vitro and in vivo antimalarial evaluation

Simultaneous analysis of metformin and cyanoguanidine by capillary zone electrophoresis and its application in a stability study

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