Diltiazem

Recently, solid lipid Nano-particles have received much attention by the researchers owing to its biodegradability, biocompatibility and the ability to deliver a wide range of drugs. The aim of the present study was to design Diltiazem solid lipid Nano-particles and to evaluate them. Diltiazem solid lipid Nano-particles were prepared by hot homogenization technique using different lipids (Tristearin, GMS and Comprital), soy lecithin as stabilizers and tween 80, Poloxamer as surfactants. The Nano-particles were evaluated for particle size & PDI, zeta potential, entrapment efficiency and in vitro drug release. The particle size ranged from 49.7 to 523.7 nm. PDI of all formulations were good within the range of 0.189 to 0.427. The zeta potential ranged from -10.5 to -29.6 Mv, Entrapment efficiency of all formulations were observed was in the range of 78.68 to 95.23 %. The cumulative percentage release of Diltiazem from different Diltiazem Nano-particles varied from 53.36 to 88.74% depending upon the drug lipid ratio and the type of lipid used. The average percentage of drug released from different SLNs after 24 hours showed in the following order: F9 (53.35%) < F6 (56.75%) < F4 (61.74%) < F7 (63.8%) < F5(67.77%) < F8(69.04%) < F3(75.31%) < F1(79.36%)

A simple, sensitive, selective and rugged liquid chromatography coupled with mass spectrometry (LCMS/MS) method for quantification of Diltiazem and its metabolites, N-desmethyl Diltiazem, desacetyl Diltiazem in human plasma was developed and validated. The chromatography was developed using Luna 5 μ, C18, 100×4.60 mm column having a mobile phase of Acetonitrile: 0.1% formic acid (85:15 % v/v). The flow rate was 0.5 ml/min at a column temperature of 50 ± 5º C. Electron spray ionization technique in positive mode was selected to improve the selectivity and sensitivity required for this application. The retention times of Diltiazem, desmethyl Diltiazem, desacetyl Diltiazem were 2.5, 2.0 and 2.5 minutes respectively. The method was validated for linearity, precision, accuracy, specificity, sensitivity, matrix effect, dilution integrity, ruggedness, injection reproducibility and stability. Calibration curves during the course of validation were found to be linear for Diltiazem, desmethyl Diltiazem, desacetyl Diltiazem in the ranges of 0.604-603.902, 0.303-303.274 and 0.299-299.489 ng/mL with correlation coefficient ≥ 0.9969, 0.9958 and 0.9970 respectively and by using a 1/x2 weighted least square regression analysis of standard plots associated with ten point calibration standards. The precision and mean accuracy were within the acceptable limits. Keywords: Diltiazem; desmethyl Diltiazem, desacetyl Diltiazem; LCMS/MS; Validation.

A simple, sensitive, selective and rugged liquid chromatography coupled with mass spectrometry (LC/MS/MS) method for quantification of Diltiazem and its metabolites, N-desmethyl Diltiazem, desacetyl Diltiazem in human plasma was developed and validated. The chromatography was developed using Luna 5 μ, C18, 100×4.60 mm column having a mobile phase of Acetonitrile: 0.1 % formic acid (85:15 % v/v). The flow rate was 0.5 ml/min at a column temperature of 50 ± 5º C. Electron spray ionization technique in positive mode was selected to improve the selectivity and sensitivity required for this application. The retention times of Diltiazem, desmethyl Diltiazem, desacetyl Diltiazem were 2.5, 2.0 and 2.5 minutes respectively. The method was validated for linearity, precision, accuracy, specificity, sensitivity, matrix effect, dilution integrity, ruggedness, injection reproducibility and stability. Calibration curves during the course of validation were found to be linear for Diltiazem, desmethyl Diltiazem, desacetyl Diltiazem in the ranges of 0.604-603.902, 0.303-303.274 and 0.299-299.489 ng/mL with correlation coefficient ≥ 0.9969, 0.9958 and 0.9970 respectively and by using a 1/x2 weighted least square regression analysis of standard plots associated with ten point calibration standards. The precision and mean accuracy were within the acceptable limits.