Abstract
A simple and rapid reverse phase high performance liquid chromatography (RP-HPLC) method was developed and validated for quantitative determination of Isoniazid (INH) in plasma, brain, liver and kidney samples and in solid lipid nanoparticles (SLNs). Isoniazid was analyzed by using a reverse phase column (Waters, Symmetry shield RP- 18, 4.6 mm x 150 cm, 5 microns), with mobile phase consisting of 0.1 M phosphate buffer, pH 5 (pH adjusted with ortho phosphoric acid) and methanol and the detection was made at 254 nm using Photo Diode Array detector at a temperature of 30°C (sample 4°C). The retention time for INH was around 3.5 minutes. The calibration curves were linear (r2 0.9998) over a concentration range from 250 ng to 25,000 ng/mL. Limit of detection (LOD) was 150 ng/mL and the Limit of quantitation (LOQ) was 200 ng/mL for plasma and tissue homogenates (brain, liver and kidney). Intra and inter-day variability’s (RSD) for extraction of INH from plasma and other tissue homogenates were less than 5% and accuracy was ± 5%. The results established lectivity and suitability of the method for pharmacokinetic studies of INH from INH SLNs.
Highlights
Isoniazid (INH) belongs to the class of nucleoside reverse transcriptase inhibitor and is the one of the first line agents reserved by ‘WHO’ for the treatment of tuberculosis [1].Isoniazid is a Biopharmaceutical Classification System (BCS) class III drug reported to have aqueous solubility of 140 mg/ml [2] and log P of -0.64 (2008)
Polymeric nanoparticles and solid lipid nanoparticles of isoniazid are reported with an aim of reducing the dose and improving the permeability of isoniazid [512]
Linearity: Calibration curve was constructed with 5 concentrations ranging from 0.250 to 25.000 μg ml-1 in blank solid lipid nanoparticles (SLNs), plasma and tissue homogenates
Summary
Isoniazid is a Biopharmaceutical Classification System (BCS) class III drug (high solubility and low permeability) reported to have aqueous solubility of 140 mg/ml [2] and log P of -0.64 (2008). The low permeability [3] and short t1/2 [2] and fast elimination (50 to 70% [4]) potentiated with a high dose (300 mg/adult) makes it a suitable candidate for delivery by a novel biodegradable drug delivery system, solid lipid nanoparticles (SLNs). Liposomal systems of isoniazid were reported in late 90’s for reducing the dose and dosing frequency [5]. Polymeric nanoparticles and solid lipid nanoparticles of isoniazid are reported with an aim of reducing the dose and improving the permeability of isoniazid [512]. Ingredients like lipids and fatty acids which mimic the natural cell wall components are reported to help in rapid uptake of the NDDS into the mycobacterium and a consequent release of the drug directly inside the mycobacterium achieving both targetability and a facilitative permeation into the mycobacterium [13]
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