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The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid (SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology. The three-dimensional (3D) information of SA particles in tablets was detected by a quantitative and non-invasive 3D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography (SR-μCT). SA particles in glipizide tablets prepared by using unmodified SA (GUT), reprocessed SA (GRT), as well as reference listed drug (RLD) of glipizide tablets were analyzed by SR-μCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-μCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering. [ABSTRACT FROM AUTHOR]

The microsphere was a primary particulate system for taste-masking with unique structural features defined by production process. In this article, ibuprofen lipid microspheres of octadecanol and glycerin monostearate were prepared to mask the undesirable taste of ibuprofen via three kinds of spray congealing processes, namely, air-cooling, water-cooling and citric acid solution-cooling. The stereoscopic and internal structures of ibuprofen microspheres were quantitatively analyzed by synchrotron radiation X-ray micro-computed tomography (SR-µCT) to establish the relationship between the preparation process and microsphere architectures. It was found that the microstructure and morphology of the microspheres were significantly influenced by preparation processes as the primary factors to determine the release profiles and taste-masking effects. The sphericity of ibuprofen microspheres congealed in citric acid solution was higher than that of other two and its morphology was more regular than that being congealed in air or distilled water, and the contact angles between congealing media and melted ibuprofen in octadecanol and glycerin monostearate well demonstrated the structure differences among microspheres of three processes which controlled the release characteristics of the microspheres. The structure parameters like porosity, sphericity, and radius ratio from quantitative analysis were correlated well with drug release behaviors. The results demonstrated that the exterior morphology and internal structure of microspheres had considerable influences on the drug release behaviors as well as taste-masking effects. [ABSTRACT FROM AUTHOR]

Polyphyllin I (PPI), a natural steroidal saponin originating from rihzome of Paris polyphylla, is a potential anticancer candidate. Previous pharmacokinetics study showed that the oral bioavailability of PPI was very low, which suggested that certain amount of PPI might be metabolized in vivo. However, to date, information regarding the final metabolic fates of PPI is very limited. In this study, metabolites of PPI and their pharmacokinetics in rats were investigated using UPLC-QTOF-MS/MS and LC-TQ-MS/MS. A total of seven putative metabolites, including six phase I and one phase II metabolites, were detected and identified with three exact structures by comparison with authentic standards for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. The pharmacokinetics of prosapogenin A, trillin and diosgenin, three deglycosylation metabolites of PPI with definite anticancer effects, were further studied, which suggested that the metabolites underwent a prolonged absorption and slower elimination after intragastric administration of PPI at the dose of 500 mg/kg. This study provides valuable and new information on the metabolic fate of PPI, which will be helpful in further understanding its mechanism of action. [ABSTRACT FROM AUTHOR]

ABSTRACT A sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of asperosaponin VI in beagle dog plasma using glycyrrhizic acid as the internal standard (IS). Plasma samples were simply pretreated with methanol for deproteinization. Chromatographic separation was performed on a Hedera ODS-2 column using mobile phase of methanol-10 m m ammonium acetate buffer solution containing 0.05% acetic acid (71:29, v/v) at a flow rate of 0.38 mL/min. Asperosaponin VI and the IS were eluted at 2.8 and 1.9 min, respectively, ionized in negative ion mode, and then detected by multiple reaction monitoring. The detection used the transitions of the deprotonated molecules at m/ z 927.5 → 603.4 for asperosaponin VI and m/ z 821.4 → 645.4 for glycyrrhizic acid (IS). The assay was linear over the concentration range of 0.15-700 ng/mL and was successfully applied to a pilot pharmacokinetic study in beagle dogs. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

To study the pharmacokinetics, excretion characteristics and plasma protein binding rate of asperosaponin VI (A-VI) and its active metabolite hederagenin (M1). A-VI and M1 concentrations in plasma, bile, urine and feces were determined by established LC-MS/MS to calculate the pharmacokinetic parameters. The plasma protein binding rate of A-VI was determined by equilibrium dialysis method. the double peaks was observed in the A-VI plasma concentration-time curve, after rats were orally administered with low, medium and high doses of A-VI (0.03, 0.09, 0.27 g x kg(-1)). The Cmax1 and Cmax2 of A-VI were (28.88 +/- 49.78) and (4.480 +/- 1.872) microg x L(-1), (35.19 +/- 23.53) and (22.11 +/- 16.15) microg x L(-1), (73.37 +/- 37.28) and (132.2 +/- 160.7) microg x L(-1), respectively. The AUC0-t, of A-VI were (43.21 +/- 37.32), (133.9 +/- 102.5) and (779.6 +/- 876.9) microg x h x L(-1), respectively. The t1/2 of A-VI were (3.3 +/- 0.8), (3.2 +/- 2.3) and (4.5 +/- 1.2) h, respectively. The Cmax of M1 were (16.03 +/- 9.336), (26.41 +/- 11.95) and (28.71 +/- 5.874) microg x L(-1), respectively. The AUC0-t, of M1 were (105.6 +/- 73.60), (260.0 +/-153.9) and (323.1 +/- 107.9) microg x h x L(-1), respectively. The t1/2 of M1 were (4.1 +/- 3.4), (4.4 +/- 2.3), (3.9 +/- 0.9) h, respectively. No significant gender difference was found in the in vivo pharmacokinetics of A-VI and M1. There was no accumulation of A-VI and M1 after multiple administrations of A-VI (0.09 g x kg(-1)). After oral administration of A-VI, the double peaks were also observed in biliary and urinary excretion rate-time curves for A-VI. M1 was detected in the feces samples at 6 h after oral administration. The average plasma protein binding rate of A-VI was 92. 9% in rats.