Preparation and evaluation of tamsulosin hydrochloride sustained-release pellets modified by two-layered membrane techniques

The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques.Centrifugal granulator and fluidizedbed coater were employed to prepare drug-loaded pellets and to employ two-layered membrane coating respectively.The prepared pellets were evaluated for physicochemical characterization,subjected to differential scanning calorimetry(DSC)and in vitro release of different pH.Different release models and scanning electron microscopy(SEM)were utilized to analyze the release mechanism of Harnual■ and home-made pellets.By comparing the dissolution profiles,the ratio and coating weight gain of Eudragit■ NE30D and Eudragit■ L30D55 which constitute the inside membrane were identified as 18:1 and 10%-11%.The coating amount of outside membrane containing Eudragit■ L30D55 was determined to be 0.8%.The similarity factors(f_(2))of home-made capsule and commercially available product(Harnual■)were above 50 in different dissolution media.DSC studies confirmed that drug and excipients had good compatibility and SEM photographs showed the similarities and differences of coating surface between Harnual■ and self-made pellets before and after dissolution.According to Ritger-Peppas model,the two dosage form had different release mechanism.

LCeMS/MS assay for pitavastatin in human plasma and subsequent application to a clinical study in healthy Chinese volunteers

Arapid,selective and sensitive liquid chromatography-tandem massspectrometry(LC-MS/MS)method has been developed and validated for the determination of pitavastatin in humanplasma.Following a liquid-liquid extraction,both the analytes and internal standard telmisartan were separated on a Luna C_(18) column with a mobile phase consisted of acetonitrile-methanol-1% formic acid in water(50:25:25,v/v/v).Mass spectrometric detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring(MRM)of the transitions at m/z 421.9→290.1 for pitavastatin and m/z 515.2→276.2 for the IS.The assay for pitavastatin showed good linearity(r≥0.99)over the ranges 0.2-400 ng/ml,with a lower limit of quantitation of 0.2 ng/ml.Accuracy and precision for the assay were determined by calculating the intra-and inter-batch variation of quality control(QC)samples at three concentration levels,with relative standard deviations(RSD)of less than 15%for both analytes.The mean extraction recovery of pitavastatin and IS were both above 70%.Matrix effect hasn't been found in this method.The method has been successfully applied to a clinic pharmacokinetic study of pitavastatin administered.