No abstract

The objective of carrying out this research work was to investigate the effect of chirality on the stereospecific dissolution of amlodipine from various marketed racemic amlodipine besylate tablets. Amlodipine is a calcium ion influx inhibitor which is used in the treatment of hypertension and angina. In this study dissolution of various marketed tablets was performed using USP type II apparatus in 0.1 N HCl at 75 rpm with temperature being maintained at 37±0.5 o C. Chromatographic separation of amlodipine enantiomers was performed using HPLC equipped with UV-Visible detector using Chiral AGP column (100 x 4.6 mm I.D., 5µ particle size). There was no significant difference between the cumulative drug release profiles of S and R enantiomers (p>0.05) in 16 out of 20 marketed racemic amlodipine besylate tablets except for amlong, stamlo-5, amlopin-5 and amcard (p<0.05). Though the stereospecificity in the dissolution was found with the four brands i.e., amlong, stamlo-5, amlopin-5 and amcard, the stereospecificity found with Stamlo-5 was quite opposite to the stereospecificity of amlong, amlopin-5 and amcard because the dissolution of R enantiomer of amlong, amlopin-5 and amcard was significantly more compared to their S enantiomer where as in the case of stamlo-5 the dissolution of S enantiomer was more compared to its R enantiomer.

The objective of the current investigation was to study the degradation behavior of irinotecan hydrochloride under different International Conference on Harmonization (ICH) recommended stress conditions using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry and to establish a validated stability-indicating reverse-phase ultra-performance liquid chromatographic method for the quantitative determination of irinotecan hydrochloride and its seven impurities and degradation products in pharmaceutical dosage forms. Irinotecan hydrochloride was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Irinotecan hydrochloride was found to degrade significantly in oxidative and base hydrolysis and photolytic degradation conditions. The degradation products were well resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. Chromatographic separation was achieved on a Waters Acquity BEH C8 (100 × 2.1 mm) 1.7-µm column with a mobile phase containing a gradient mixture of solvent A (0.02M KH(2)PO(4) buffer, pH 3.4) and solvent B (a mixture of acetonitrile and methanol in the ratio of 62:38 v/v). The mobile phase was delivered at a flow rate of 0.3 mL/min with ultraviolet detection at 220 nm. The run time was 8 min, within which irinotecan and its seven impurities and degradation products were satisfactorily separated. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of irinotecan hydrochloride in pharmaceutical dosage forms.

The objective of this work was preparation of inclusion complexes of amlodipine base and its besylate and maleate salts with hydroxy propyl ß-cyclodextrin to improve the dissolution and to investigate the stereospecific dissolution of amlodipine enantiomers. Different techniques like physicl mixing, kneading and solvent evaporation were tried to prepare the inclusion complexes of amlodipine base and its besylate and maleate salts with hydroxy propyl β-cyclodextrin (HPBC). Dissolution of prepared inclusion complexes was performed using USP type II apparatus in 0.1 N HCl at 75 rpm with temperature being maintained at 37±0.5 o C. Chromatographic separation of amlodipine enantiomers was performed on a Shimadzu HPLC System (Japan) equipped with UV-Visible detector using Chiral AGP column (100 x 4.6 mm I.D., 5µ particle size). Improvement in the dissolution was found with racemic amlodipine base where as no improvement was found with amlodipine besylate and maleate salts (p>0.05). This indicates the formation of inclusion complexes with only racemic amlodipine base (p< 0.05) which was also supported by their FTIR and DSC spectra. In case of physical mixing no inclusion complexes were formed even with enantiomers of amlodipine base (p>0.05). Stereospecific dissolution was observed with pure enantiomers of amlodipine base when its inclusion complexes were prepared by solvent evaporation method with l:1 & 1:2 molar ratios but not with 1:3 molar ratio.