Abstract
A simple and sensitive HPLC method was developed and validated for the quantification of haloperidol in solid lipid nanoparticles (SLNs). The developed method was used for detection of shelf life of haloperidol in SLNs. Calibration curve of haloperidol was also constructed in rat plasma using loratidine as internal standard. In vivo studies were performed on rats and concentration of haloperidol in brain and blood was measured for the determination of various pharmacokinetic and hence brain targeting parameters. Chromatogram separation was achieved using C18 column as stationary phase. The mobile phase consisted of 100 mM/L potassium dihydrogen phosphate-acetonitrile-TEA (10:90:0.1, v/v/v) and the pH was adjusted with o-phosphoric acid to 3.5. Flow rate of mobile phase was 2 mL/minute and eluents were monitored at 230 nm using UV/VIS detector. The method was validated for linearity, precision, accuracy, reproducibility, limit of detection (LOD) and limit of quantification (LOQ). Linearity for haloperidol was in the range of 1-16 µg/mL. The value of LOD and LOQ was found to be 0.045 and 0.135 μg/mL respectively. The shelf life of SLNs formulation was found to be 2.31 years at 4 oC. Various parameters like drug targeting index (DTI), drug targeting efficiency (DTE) and nose-to-brain direct transport (DTP) were determined for HP-SLNs & HP-Sol administered intranasally to evaluate the extent of nose-to-brain delivery. The value of DTI, DTE and DTP for HP-SLNs was found to be 23.62, 2362.43 % and 95.77% while for HP-Sol, values were 11.28, 1128.61 % and 91.14 % respectively.
Highlights
Haloperidol is an orally administered dopamine inverse agonist of the typical antipsychotic class of medication that chemically belongs to butyrophenone group (Gajski, Geri, Garaj-Vrhovac, 2014)
For the determination of pharmacokinetic and brain targeting parameters after intranasal administration of haloperidol loaded solid lipid nanoparticles (HP-SLNs) and plain drug solution (HP-Sol), the calibration curve of haloperidol in rat plasma was prepared by the reported RP-high performance liquid chromatography (HPLC) method (Jain et al, 2011)
The concentration of haloperidol had been earlier determined by HPLC method using methanol-water (63:37, v/v) containing 0.2 M ammonium acetate as mobile phase and diphenylamine as internal standard (IS) (Miyazaki et al, 1981)
Summary
Haloperidol is an orally administered dopamine inverse agonist of the typical antipsychotic class of medication that chemically belongs to butyrophenone group (Gajski, Geri, Garaj-Vrhovac, 2014). Various analytical techniques have been used for determination of haloperidol in pharmaceutical formulations. These include high performance liquid chromatography (HPLC) (Wate, Borkar, 2009), high performance thin-layer chromatography (HPTLC) (Sigrid et al, 2007), 19F NMR spectroscopy (Mojtaba et al, 2007), square-wave adsorptive stripping voltammetry. Non-aqueous titrimetric method has been developed for haloperidol determination in pharmaceutical preparations (European Pharmacopoeia, 2002). The aim of present study was to develop and validate a new HPLC method for the quantitative analysis of haloperidol in SLNs. The different analytical performance parameters such as linearity, precision, accuracy, reproducibility, limit of detection (LOD) and limit of quantification (LOQ) were determined according to ICH Q2 (R1) guidelines (ICH, 2005; Dalila et al, 2012). For the determination of pharmacokinetic and brain targeting parameters after intranasal administration of haloperidol loaded solid lipid nanoparticles (HP-SLNs) and plain drug solution (HP-Sol), the calibration curve of haloperidol in rat plasma was prepared by the reported RP-HPLC method (Jain et al, 2011)
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